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In this paper, we numerically investigate the orbit dynamics of three-dimensional symmetric Janus drops in shear flow using an improved ternary-fluids phase field method, focusing on how drop deformation and initial orientation affect the orbit drift of two configurations of Janus drops: dumbbell-shaped and near-spherical. We find that the motion of dumbbell-shaped drops eventually evolves into tumbling, while near-spherical drops attain stable spinning. We attribute this bifurcation in orbit drift to contrasting deformation dynamics and shape-dependent hydrodynamics of the two configurations. Specifically, the drift bifurcation is closely related to the aspect ratio of Janus drops at equilibrium, giving rise to two distinct mechanisms: (1) coupling between outer interface deformation and the surrounding flow field; and (2) interplay between inner interface deformation and vortices enclosed within the drop. In addition, we observe that for the dumbbell-shaped Janus drops with different aspect ratios, their tumbling dynamics resembles ellipsoids in shear flow. Moreover, the trajectories of the dumbbell-shaped Janus drops during orbit drift collapse onto a universal curve, independent of their initial orientations, and significant deformation and inertia accelerate the orbit transition. To quantitatively evaluate the effect of drop deformation on the orbit drift of the dumbbell-shaped Janus drops, we propose an effective aspect ratio model based on the drop shapes at equilibrium and at the maximum elongation. By incorporating the effective aspect ratio into Jeffery’s theory for solid particles, we accurately predict the rotation period and angular velocity of Janus drops in the tumbling regime and during the orbit drift, especially for drops with linear deformation. Moreover, the orbit parameter $C$ is found to vary exponentially with time for drops with linear deformation, while the time variation of $C$ transits from one exponential function to another for drops with nonlinear deformation.
Major depressive disorder (MDD) patients exhibit a mood-congruent emotional processing bias within the amygdala toward negative facial stimuli at both unconscious and conscious levels. Therefore, our study aimed to investigate the temporal and spatial dynamics of amygdala along with its interactions with the whole brain during implicit and explicit conditions in MDD.
Methods
Thirty MDD patients and 26 healthy controls (HCs) underwent magnetoencephalography (MEG) recordings and performed implicit and explicit emotional face recognition tasks with happy, sad, and neutral facial expressions. Using the amygdala as a seed region, time frequency representations (TFR) and functional connectivity (FC) were calculated. Pearson correlation analyses measured the relationship between TFR and FC values with clinical symptoms.
Results
During implicit processing, MDD patients exhibited left amygdala activation in the gamma power (60–70 Hz) before 250 ms in response to sad facial stimuli compared to HCs. In the implicit mode, there were increased FC between the right amygdala and several brain regions in the occipitoparietal lobes, as well as higher FC between the left amygdala and putamen in MDD patients. Additionally, the right amygdala was positively correlated with the severity of depression and anxiety during implicit processing.
Conclusions
MDD patients had lateralized amygdala activation in response to sad facial expressions during unconscious emotional recognition of facial stimuli. Our study provided valuable insights into the spatiotemporal dynamics of facial emotional recognition associated with depressive and anxiety-related cognitive bias during implicit and explicit processing.
Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.
Methods
A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.
Results
Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.
Conclusions
Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.
Data on aortic valve outcomes following surgical repair of doubly committed subarterial ventricular septal defect remain limited.
Methods:
This retrospective study included doubly committed subarterial ventricular septal defect patients who underwent surgical repair at our centre from 2013 to 2023. The primary outcome was the incidence of new-onset aortic regurgitation during follow-up.
Results:
A total of 320 patients were included, with a median age of 2.0 (0.9–7.2) years. Among them, 289 patients underwent surgical repair alone (repair group), and 31 received additional aortic valve surgery (repair + aortic valve surgery group). Preoperatively, 58 (18.1%) patients exhibited aortic regurgitation ≥ mild (10.7% in the repair group vs 87.1% in the repair + aortic valve surgery group, P < 0.001). The overall median follow-up was 40.5 (16.0–72.0) months. At the last follow-up, 23 (7.4%) patients had aortic regurgitation ≥ mild (3.8 vs 52.2%, P < 0.001), and 6 (1.9%) had aortic regurgitation > mild (0.3 vs 21.7%, P < 0.001). Sixteen (5.1%) patients developed new-onset aortic regurgitation during follow-up (1.7 vs 47.8%, log-rank P < 0.001), and 6 (1.9%) of them developed new-onset aortic regurgitation > mild (0.3 vs 21.7%, log-rank P < 0.001). Age, ventricular septal defect size, preoperative aortic regurgitation > mild, and maximum aortic valve flow velocity (AVmax) were related to concurrent aortic valve surgery and new-onset aortic regurgitation.
Conclusions:
Based on our retrospective data, the mid-term aortic valve outcomes after doubly committed subarterial ventricular septal defect repair were relatively satisfactory, with a low incidence of new-onset aortic regurgitation during follow-up. However, aortic valve outcomes for patients who received concurrent aortic valve surgery were less satisfactory.
Previous research has suggested bidirectional relations between depressive symptoms and both internal and external core beliefs (self-esteem and optimism, respectively) in adolescence. However, little work has examined the cultural commonality versus specificity of these developmental pathways in adolescence across diverse contexts. To address this gap, the current study traced bidirectional associations among depressive symptoms and two forms of core beliefs (self-esteem and optimism) in adolescents from 12 cultural groups in nine countries. Longitudinal data were collected from 1,090 adolescents at ages 15 and 17. Significant associations emerged between age 15 depressive symptoms and both age 17 core beliefs across all cultural groups except Sweden. No significant associations between age 15 core beliefs and age 17 depressive symptoms were found in the multigroup model. However, the pathways from core beliefs to depressive symptoms and from depressive symptoms to core beliefs did not significantly differ in strength. These findings provide cross-cultural evidence for the scar theory (depressive symptoms → core beliefs), but no clear support for the vulnerability theory (core beliefs → depressive symptoms), perhaps due to the measurement and stability of depression. These findings have implications for understanding the adolescent development of psychopathology and cognitions, such as core beliefs, across diverse cultures.
Antimicrobial resistance (AMR) is a global health challenge, highlighting the need for antibiotic stewardship policies. We evaluated the impact of the National Action Plan to Contain Antimicrobial Resistance (2022–2025) on antibiotic use among primary healthcare institutions (PHIs) in Central China.
Design:
A segmented interrupted time-series analysis from January 2021 to December 2023.
Methods:
We collected data from 1510 PHIs, by region, types of healthcare institutions and medication type, assessing antibiotic consumption using defined daily doses per 1000 inhabitants per day and the quality by the percentage of broad-spectrum antibiotics.
Results:
Post-intervention, antibiotic consumption declined by −35.96% (95%CI: –49.34 to –22.57), and the proportion of broad-spectrum antibiotic use decreased by –41.97% (–61.74 to –22.20). Consumption dropped significantly in both moderately developed areas and underdeveloped areas, while highly developed areas saw the largest reduction in broad-spectrum antibiotic use. Rural PHIs also showed notable declines in both overall antibiotic consumption and broad-spectrum usage.
Conclusions:
The policy was associated with a reduction in antibiotic use across PHIs, though regional disparities in its implementation suggest uneven benefits.
Studies highlight the thalamus as a key region distinguishing early- from late-onset obsessive-compulsive disorder (OCD). While structural thalamic correlates with OCD onset age are well-studied, resting-state functional connectivity (rsFC) remains largely unexplored. This study examines thalamic subregional rsFC to elucidate pathophysiological differences in OCD based on different onset times.
Methods
The study comprised 85 early-onset OCD (EO-OCD) patients, 94 late-onset OCD (LO-OCD) patients, and 94 age- and sex-matched healthy controls (HCs). rsFC analysis was conducted to assess thalamic connectivity across seven subdivisions among the groups.
Results
Both EO-OCD and LO-OCD patients exhibited increased rsFC between the primary motor thalamus and the posterior central gyrus and between the thalamic premotor and the supplementary motor areas. EO-OCD patients showed significantly stronger rsFC between the prefrontal thalamus (Ptha) and the middle frontal gyrus (MFG) compared to both LO-OCD patients and HCs. In contrast, LO-OCD patients demonstrated reduced rsFC between the Ptha and the inferior parietal lobule (IPL) compared to EO-OCD patients and HCs. Additionally, the rsFC between the Ptha and both the MFG and IPL was negatively correlated with age of onset, with earlier onset linked to stronger connectivity.
Conclusion
These findings reveal both shared and distinct thalamic connectivity patterns in EO-OCD and LO-OCD patients. Sensory-motor networks exhibiting thalamic hyperconnectivity are critical for the manifestation of OCD, regardless of age of onset. The frontal–parietal network and thalamic hyperconnectivity may present a compensatory mechanism in EO-OCD patients, while hypoconnectivity with the frontoparietal network may reflect a neural mechanism underlying LO-OCD.
Posttraumatic stress disorder (PTSD) exhibits marked heterogeneity, with relational (R; interpersonal) and nonrelational (NR; environmental) trauma subtypes demonstrating distinct psychopathological trajectories. Despite clinical recognition of these differences, their neurobiological underpinnings of emotion processing remain poorly understood. Guided by the Nested Hierarchical Model of Self (NHMS) – which posits trauma-type-specific disruptions in hierarchical self-processing systems – this study investigated neural mechanisms differentiating among PTSD subtypes during implicit emotion regulation.
Methods
A sample of 122 participants, including patients with PTSD (R: n = 51; NR: n = 29) and trauma-exposed controls matched by trauma type (R: n = 22; NR: n = 20), underwent functional magnetic resonance imaging while performing the Shifted Attention Emotion Appraisal Task. Behavioral assessments and trauma typology coding were complemented by regions of interest (ROI)-based and whole-brain analyses.
Results
Results revealed that PTSD-R showed hypoactivation in right superior frontal gyrus (during implicit emotion regulation; BA9; p = 0.049, ηp2 = 0.033), whereas PTSD-NR exhibited hyperactivation in fusiform (during emotion modulation by attention shifting; p = 0.036, ηp2 = 0.037). Symptom severity inversely correlated with social support (r = −0.353 to −0.417, p < 0.01), with relational PTSD reporting the lowest support (p < 0.001). Across conditions, dorsolateral prefrontal clusters (BA8/9) demonstrated anticorrelations with default-mode regions (r = −0.272 to −0.549, p < 0.01) aligning with NHMS’ predictive coding framework.
Conclusions
These findings validate trauma-type-specific neural hierarchies, suggesting relational trauma disrupts top-down self-identity schemas, while NR trauma amplifies bottom-up threat detection. The study advances precision psychiatry by linking implicit regulation biomarkers to targeted interventions – cognitive restructuring for PTSD-R and interoceptive recalibration for PTSD-NR.
Depression and anxiety are prevalent mental health disorders. While sleep duration has been extensively studied, sleep regularity may play a critical role. We aimed to examine associations between objectively measured sleep regularity and incident depression and anxiety and to investigate whether meeting recommended sleep duration modifies these associations.
Methods
In 79,666 UK Biobank participants without baseline depression or anxiety, wrist accelerometers worn for 7 days yielded a sleep regularity index (SRI) and average sleep duration. SRI was categorized as irregular (≤51), moderately irregular (52–70), or regular (≥71). Sleep duration was classified by age-specific recommendations (7–9 hours for ages 18–64 years; 7–8 hours for over 65 years). Cox regression models assessed associations between sleep parameters and mental health outcomes.
Results
During a median follow-up of 7.5 years, 1,646 participants developed depression, and 2,097 developed anxiety. Compared to irregular sleepers, regular sleepers had a 38% lower depression risk (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.52–0.73) and a 33% lower anxiety risk (HR, 0.67; 95%CI, 0.58–0.77). Participants with both irregular sleep and nonrecommended duration exhibited the highest risks (depression HR, 1.91; 95%CI, 1.55–2.35; anxiety HR, 1.61; 95%CI, 1.35–1.93). Notably, irregular sleepers who met duration guidelines still faced elevated risks (depression HR, 1.48; 95%CI, 1.18–1.86; anxiety HR, 1.35; 95%CI, 1.11–1.64).
Conclusions
Greater sleep regularity is independently associated with lower depression and anxiety risk regardless of sleep duration, suggesting that sleep–wake consistency should be considered in mental health promotion strategies alongside traditional sleep duration recommendations.
Seasonal changes and cyclical human activities (such as periodic fishing bans, Wolbachia-based mosquito population control, and school term breaks) have significant impacts on population dynamics. We propose a general switching dynamical model to describe these periodic changes. The existence, uniqueness and stability of positive periodic solutions are thoroughly investigated. The results are stated in terms of an introduced threshold value. To demonstrate their practicability, the obtained results are applied to two biological situations.
Major depressive disorder (MDD) and psychostimulant use disorder (PUD) are common, disabling psychopathologies that pose a major public health burden. They share a common behavioral phenotype: deficits in inhibitory control (IC). However, whether this is underpinned by shared neurobiology remains unclear. In this meta-analytic study, we aimed to define and compare brain functional alterations during IC tasks in MDD and PUD.
Methods
We conducted a systematic literature search on IC task-based functional magnetic resonance imaging studies in MDD and PUD (cocaine or methamphetamine use disorder) in PubMed, Web of Science, and Scopus. We performed a quantitative meta-analysis using seed-based d mapping to define common and distinct neurofunctional abnormalities.
Results
We identified 14 studies comparing IC-related brain activation in a total of 340 MDD patients with 303 healthy controls (HCs), and 11 studies comparing 258 PUD patients with 273 HCs. MDD showed disorder-differentiating hypoactivation during IC tasks in the median cingulate/paracingulate gyri relative to PUD and HC, whereas PUD showed disorder-differentiating hypoactivation relative to MDD and HC in the bilateral inferior parietal lobule. In conjunction analysis, hypoactivation in the right inferior/middle frontal gyrus was common to both MDD and PUD.
Conclusions
The transdiagnostic neurofunctional alterations in prefrontal cognitive control regions may underlie IC deficits shared by MDD and PUD, whereas disorder-differentiating activation abnormalities in midcingulate and parietal regions may account for their distinct features associated with disturbed goal-directed behavior.
The incorporation of trace metals into land snail shells may record the ambient environmental conditions, yet this potential remains largely unexplored. In this study, we analyzed modern snail shells (Cathaica sp.) collected from 16 sites across the Chinese Loess Plateau to investigate their trace metal compositions. Our results show that both the Sr/Ca and Ba/Ca ratios exhibit minimal intra-shell variability and small inter-shell variability at individual sites. A significant positive correlation is observed between the shell Sr/Ca and Ba/Ca ratios across the plateau, with higher values being recorded in the northwestern sites where less monsoonal rainfall is received. We propose that shell Sr/Ca and Ba/Ca ratios, which record the composition of soil solution, may be controlled by the Rayleigh distillation in response to prior calcite precipitation. Higher rainfall amounts may lead to a lower degree of Rayleigh distillation and thus lower shell Sr/Ca and Ba/Ca ratios. This is supported by the distinct negative correlation between summer precipitation and shell Sr/Ca and Ba/Ca ratios, enabling us to reconstruct summer precipitation amounts using the Sr/Ca and Ba/Ca ratios of Cathaica sp. shells. The potential application of these novel proxies may also be promising for other terrestrial mollusks living in the loess deposits globally.
The high comorbidity of major depressive disorder (MDD), anxiety disorders (ANX), and post-traumatic stress disorder (PTSD) complicates the study of their structural neural correlates, particularly in white matter (WM) alterations. Using fractional anisotropy (FA), this meta-analysis aimed to identify both unique and shared WM characteristics for these disorders by comparing them with healthy controls (HC). The aggregated sample size across studies includes 3,661 individuals diagnosed with MDD, ANX, or PTSD and 3,140 HC participants. The whole-brain analysis revealed significant FA reductions in the corpus callosum (CC) across MDD, ANX, and PTSD, suggesting a common neurostructural alteration underlying these disorders. Further pairwise comparisons highlighted disorder-specific differences: MDD patients showed reduced FA in the middle cerebellar peduncles and bilateral superior longitudinal fasciculus II relative to ANX patients and decreased FA in the CC extending to the left anterior thalamic projections (ATPs) when compared with PTSD. In contrast, PTSD patients exhibited reduced FA in the right ATPs compared to HC. No significant FA differences were observed between ANX and PTSD or between ANX and HC. These findings provide evidence for both shared and unique WM alterations in MDD, ANX, and PTSD, reflecting the neural underpinnings of the clinical characteristics that distinguish these disorders.
Femoral neck bone mineral density (FNBMD) is a high risk factor for femoral head fractures, and coffee intake affects bone mineral density, but the effect on FNBMD remains to be explored. First, we conducted an observational study in the National Health and Nutrition Examination Survey and collected data on coffee intake, FNBMD, and sixteen covariates. Weight linear regression was used to explore the association of coffee intake with FNBMD. Then, Mendelian randomisation (MR) was used to explore the causal relationship between coffee intake and FNBMD, the exposure factor was coffee intake, and the outcome factor was FNBMD. The inverse variance weighting (IVW) method was used for the analysis, while heterogeneity tests, sensitivity, and pleiotropy analysis were performed. A total of 5 915 people were included in the cross-sectional study, including 3 178 men and 2 737 women. In the completely adjusted model, no coffee was used as a reference. The ORs for the overall population at ‘< 1’, ‘1–<2’, ‘2–<4’, and ‘4+’ (95% CI) were 0.02 (–0.01, 0.04), 0.00 (–0.01, 0.02), –0.01 (–0.02, 0.00), and 0.00 (–0.01, 0.02), respectively. The male and female population showed no statistically significant differences in both univariate and multivariate linear regressions. In the MR study, the IVW results showed an OR (95% CI) of 1.06 (0.88–1.27), a P-value of 0.55, and an overall F-value of 80.31. The heterogeneity, sensitivity analyses, and pleiotropy had no statistical significance. Our study used cross-sectional studies and MR to demonstrate that there is no correlation or causal relationship between coffee intake and FNBMD.
This paper introduces a novel ray-tracing methodology for various gradient-index materials, particularly plasmas. The proposed approach utilizes adaptive-step Runge–Kutta integration to compute ray trajectories while incorporating an innovative rasterization step for ray energy deposition. By removing the requirement for rays to terminate at cell interfaces – a limitation inherent in earlier cell-confined approaches – the numerical formulation of ray motion becomes independent of specific domain geometries. This facilitates a unified and concise tracing method compatible with all commonly used curvilinear coordinate systems in laser–plasma simulations, which were previously unsupported or prohibitively complex under cell-confined frameworks. Numerical experiments demonstrate the algorithm’s stability and versatility in capturing diverse ray physics across reduced-dimensional planar, cylindrical and spherical coordinate systems. We anticipate that the rasterization-based approach will pave the way for the development of a generalized ray-tracing toolkit applicable to a broad range of fluid simulations and synthetic optical diagnostics.
We investigated vitamin D (VitD) nutritional status in children aged 2–6 years to provide a basis for prevention and intervention strategies for VitD deficiency (VitDD) in Chinese children.
Design:
From November 2018 to September 2019, a total of 2192 healthy children aged 2–6 years were enrolled. The serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by liquid chromatography tandem MS.
Setting:
Twelve jurisdictions in eight provinces and cities across northern and southern China were selected through stratified cluster sampling.
Participants:
2192 children aged 2–6 years were enrolled.
Results:
(1) A serum 25(OH)D concentration of 23·87 (sd 8·24) ng/ml, a VitDS rate of 65·2 %, an insufficiency rate of 29·6 % and a deficiency rate of 5·2 % were noted. (2) Age (OR = 2·22, 95 % CI 1·86, 2·64) and spring (OR = 1·35, 95 % CI 0·91, 2·01) are risk factors for VitDD and VitDI. The male (OR = 0·68, 95 % CI 0·52, 0·90), the temperature (OR = 0·89, 95 % CI 0·86, 0·93), summer (OR = 0·25, 95 % CI 0·09, 0·68), autumn (OR = 0·26, 95 % CI 0·09, 0·74) the intake of VitD supplements (OR = 0·08, 95 % CI 0·03, 0·28), the intake frequency of dairy products (OR = 0·86, 95 % CI 0·78, 0·96) and egg products (OR = 0·83, 95 % CI 0·74, 0·93) are protective factors for VitDD and VitDI.
Conclusion:
VitDD in children aged 2–6 years is still prevalent in China, but the influencing factors of VitD nutrition have changed. Latitude is not the main factor in the 25(OH)D concentrations of children aged 2–6 years; temperature, intake of eggs and dairy products and sampling season have more obvious impacts.
How do academics interested in the study of legal topics that implicate the state relate to and deal with pressures that shape the space available to conduct research? This article examines the nature and impact of such pressures on Asia-focused public law scholars who must contend with a more diverse socio-political environment than the liberal democratic setting in which questions of academic freedom are typically explored. We find that the Asia-centric academy is affected by a wide range of constraints that notably extends beyond intra-institutional demands to those put in place by the state. This article also highlights how the scholarly agenda as set in and by the Global North may reduce the room for Asia-centric research to engage in theory-building and concept formation and explores how Asia-centric scholars can assert agency in the face of pressures. We conclude by emphasising the need for greater self-reflectivity within the legal academy.
Following the 2020 cardiopulmonary resuscitation (CPR) guidelines, this study compared participant’s fatigue with the quality of manual chest compressions performed in the head-up CPR (HUP-CPR) and supine CPR (SUP-CPR) positions for two minutes on a manikin.
Methods:
Both HUP-CPR and SUP-CPR were performed in a randomized order determined by a lottery-style draw. Manual chest compressions were then performed continuously on a realistic manikin for two minutes in each position, with a 30-minute break between each condition. Data were collected on heart rate, blood pressure, and Borg rating of perceived exertion (RPE) scale scores from the participants before and after the compressions.
Results:
Mean chest compression depth (MCCD), mean chest compression rate (MCCR), accurate chest compression depth ratio (ACCDR), and correct hand position ratio were significantly lower in the HUP group than that in the SUP group. However, there were no significant differences in accurate chest compression rate ratio (ACCRR), correct recoil ratio, or mean arterial pressure (MAP) before and after chest compressions between the two groups. Changes in heart rate and RPE scores were greater in the HUP group.
Conclusion:
High-quality manual chest compressions can still be performed when the CPR manikin is placed in the HUP position. However, the quality of chest compressions in the HUP position was poorer than those in the SUP position, and rescuer fatigue was increased.
Lactylation, a new epigenetic modification, is an important way in which lactate exerts physiological functions. There is a close relationship between increased lactylations caused by lactate and glycolysis, which can interact and play a role in disease through lactate as an intermediate mediator. Current research on lactylations has focused on histone lactylation, but non-histone lactylation also has greater research potential. Due to the ubiquity of lactate modifications in mammalian cells, an increasing number of studies have found that lactate modifications play important roles in tumour cell metabolism, gene transcription and immunity.
Methods
A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.
Results
Many literatures have reported that the lactylation of protein plays an important role in human diseases and is involved in the occurrence and development of human diseases.
Conclusions
This article summary the correlation between lactylation and glycolysis, histones and non-histone proteins; the relationship between lactonation modifications and tumour development; and the current existence of lactylation-related inhibitors, with a view to provide new basic research ideas and clinical therapeutic tools for lactylation-related diseases.