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Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T‐cell dysfunction. The lactate‐induced lactylation of histone lysine residues is noteworthy, as it functions as an epigenetic modification that directly augments gene transcription from chromatin. This epigenetic modification originating from lactate effectively fosters a reliance on transcription, thereby expediting tumour progression and development. Herein, this review explores the correlation between histone lactylation and cancer characteristics, revealing histone lactylation as an innovative epigenetic process that enhances the vulnerability of cells to malignancy. Moreover, it is imperative to acknowledge the paramount importance of acknowledging innovative therapeutic methodologies for proficiently managing cancer by precisely targeting lactate signalling. This comprehensive review illuminates a crucial yet inadequately investigated aspect of histone lactylation, providing valuable insights into its clinical ramifications and prospective therapeutic interventions centred on lactylation. The lactate‐induced lactylation of histone lysine residues bridges the metabolic reprogramming and epigenetic rewiring. Histone lactylation fuels oncogene overexpression, expediting tumour progression and development. Targeting lactate signalling exhibits with therapeutic efficacy in diversified cancers.

In March 2022, the Omicron variant of SARS-CoV-2 spread rapidly in Shanghai, China. The city adopted strict non-pharmacological intervention (NPI) measures, including lockdown (implemented on March 28 in Pudong and April 1 in Puxi) and blanket PCR testing (April 4). This study aims to understand the effect of these measures. We tabulated daily case counts from official reports and fitted a two-patch stochastic SEIR model to the data for the period of March 19 to April 21. This model considered two regions in Shanghai, namely Pudong and Puxi, as the implementation of control measures in Shanghai was carried out on different dates in these regions. We verified our fitting results using the data from April 22 to June 26. Finally, we applied the point estimate of parameter values to simulate our model while varying the dates of control measure implementation, and studied the effectiveness of the control measures. Our point estimate for the parameter values yields expected case counts that agree well the data for both the periods from March 19 to April 21 and from April 22 to June 26. Lockdown did not significantly reduce the intra-region transmission rates. Only about 21% cases were reported. The underlying basic reproduction number R0 was 1.7, and the control reproduction number with both lockdown and blanket PCR testing was 1.3. If both measures were implemented on March 19, only about 5.9% infections would be prevented. Through our analysis, we found that NPI measures implemented in Shanghai were not sufficient to reduce the reproduction number to below unity. Thus, earlier intervention only has limited effect on reducing cases. The outbreak dies out because of only 27% of the population were active in disease transmission, possibly due to a combination of vaccination and lockdown.

Objective This study aimed to explore the influencing factors of survival benefit and poor prognosis of cervical cancer patients under different radiotherapy modalities. Methods A total of 186 patients with cervical cancer treated in our hospital from January 2022 to December 2023 were selected for the retrospective analysis. 126 patients received static intensity-modulated radiation therapy (IMRT) combined with cisplatin. Another 60 cases received volumetric modulated arc therapy (VMAT) combined with cisplatin. The occurrence of adverse reactions, overall survival rate, and recurrence rate were compared between the two groups. COX regression model was used to analyze the influencing factors of the poor prognosis. Results There was no difference between the disease control rate (DCR) and objective remission rate (ORR), and the overall survival and recurrence rates in the two groups. The incidence of myelosuppression was much higher in the IMRT group than the VMAT group. Compared with the survival group, the percentage of lymph node metastasis (LNM) and positive margins were significantly increased in the patients in the death group. COX multifactorial analysis confirmed that LNM and positive cutting margins were independent risk factors affecting poor prognosis after radiotherapy in cervical cancer patients ( P  < 0.05). Conclusion Both IMRT and VMAT could achieve certain effects in the treatment of cervical cancer and had similar effects in short-term survival recurrence. However, VMAT had a lower incidence of myelosuppression. LNM and positive margins were factors influencing the poor prognosis of patients.

The association between the recently updated cardiovascular health (CVH) assessment algorithm, the Life’s Essential 8 (LE8), and all-cause mortality among adults with depression remains unknown. From the National Health and Nutrition Examination Survey (NHANES) spanning 2005–2018, a cohort of 2,935 individuals diagnosed with depression was identified. Their CVH was evaluated through the LE8 score system. The investigation of mortality status utilized connections with the National Death Index up to December 31, 2019. To assess the impact of CVH on mortality risk, Kaplan-Meier survival analysis and Cox proportional hazards models, adjusting for variables related to demographics and socioeconomic status, were applied. Among 2,935 participants, those with higher CVH levels had significantly lower all-cause mortality compared to those with lower CVH levels. Cox regression analyses demonstrated that each 1-point increase in CVH score was associated with a lower risk of all-cause mortality [HR = 0.97, 95%CI:0.96–0.98]. The inverse association between CVH and mortality persisted across different demographic and socioeconomic subgroups. Higher CVH levels were associated with a significantly lower risk of all-cause mortality in individuals with depression. These findings underscore the importance of comprehensive CVH management as part of healthcare strategies for people with depression, suggesting that improving CVH may contribute to longer life expectancy in this vulnerable population.

The objective of this study was to investigate spleen pathology and immune cell subset alterations in mice exposed to acute and chronic restraint stress over various timeframes. A deeper understanding of stress-induced spleen injuries can provide new insights into the mechanisms underlying stress-induced disorders. C57BL/6N mice were restrained for different durations (1, 3, 7, 14 and 21 days) for 6–8 h daily. The control mice were observed at the same time points. Post restraint, behavioural experiments were conducted to assess spleen weight, gross morphology and microscopic histological changes. Immunohistochemical staining was used to detect changes in glucocorticoid receptor (GR) expression, immune cell subsets and cell proliferation in response to stress. Our analysis revealed significant behavioural abnormalities in the stressed mice. In particular, there was an increase in the nuclear expression of GR beginning on Day 3, and it peaked on Day 14. The spleens of stressed mice displayed a reduction in size, disordered internal tissue structure and reduced cell proliferation. NK cells and M2-type macrophages exhibited immune cell subset alterations under stress, whereas T or B cells remained unaltered. Restraint stress can lead to pathomorphological alterations in spleen morphology, cell proliferation and immune cell counts in mice. These findings suggest that stress-induced pathological changes can disrupt immune regulation during stress.

We use mathematical modeling to study the proliferation dynamics of CD4+ T cells within an immune response. This proliferation is driven by the autocrine reaction of helper T cells and interleukin-2 (IL-2), and regulated by natural regulatory T cells (nTregs). Previous studies suggested that a fratricidal mechanism is necessary to eliminate helper T cells post-infection. Contrary to this, our mathematical analysis establishes that the depletion of these cells is due to two pivotal factors: the saturation in the proliferation rate of helper CD4+ T cells at high IL-2 concentrations, and the activation rate of nTregs outpacing their death rate. This yields an excitable process, such that the proliferation starts once the helper T cell population passes a threshold. Additionally, we find that when the proliferation of nTregs lags behind their mortality, induced regulatory T cells (iTregs) are crucial to curbing the proliferation of helper CD4+ T cells.

Pairing center (PC) on each chromosome of Caenorhabditis elegans is crucial for homolog pairing and initiating synapsis. Within each PC, clusters of 11/12 bp DNA motif recruit one of four paralogous meiosis-specific proteins: ZIM-1, ZIM-2, ZIM-3, or HIM-8. However, the mechanistic basis underlying the specificity of ZIM/HIM-8-PC DNA interaction remains elusive. Here, we describe crystal structures of HIM-8, ZIM-1 and ZIM-2 DNA binding domains (ZF1, ZF2 and CTD) in complex with their cognate PC DNA motifs, respectively. These structures demonstrated the ZF1-2-CTD folds as an integrated structural unit crucial for its DNA binding specificity. Base-specific DNA-contacting residues are exclusively distributed on ZF1-2 and highly conserved. Furthermore, the CTD potentially contributes to the conformational diversity of ZF1-2, imparting binding specificity to distinct PC DNA motifs. These findings shed light on the mechanism governing PC DNA motif recognition by ZIM/HIM-8 proteins, suggesting a co-evolution relationship between PC DNA motifs and ZF1-2-CTD in shaping the specific recognition. Pairing center (PC) on each chromosome are crucial for homolog pairing and initiating synapsis in Caenorhabditis elegans . Here the authors investigate how the meiosis-specific proteins: ZIM/HIM-8 family recognize their cognate PC DNA motifs.

The adaptive immune system has two types of plasma cells (PC), long-lived plasma cells (LLPC) and short-lived plasma cells (SLPC), that differ in their lifespan. In this paper, we propose that LLPC is crucial to the clearance of viral particles in addition to reducing the viral basic reproduction number in secondary infections. We use a sequence of within-host mathematical models to show that, CD8 T cells, SLPC and memory B cells cannot achieve full viral clearance, and the viral load will reach a low positive equilibrium level because of a continuous replenishment of target cells. However, the presence of LLPC is crucial for viral clearance.

Metazoans utilize the small RNA pathway to regulate gene expression and maintain genome integrity. This pathway directs histone H3 lysine 9 tri-methylation (H3K9me3) or histone H3 lysine 27 tri-methylation (H3K27me3) at target loci to induce transcriptional gene silencing. Interestingly, some small RNAs are generated from genomic loci enriched in H3K9me3 or H3K27me3. However, the transcription mechanism of small RNA precursors from these heterochromatic regions remains unclear. In C. elegans , piRNAs originate from two genomic clusters enriched with H3K27me3 marks, which recruit the H3K27me3 reader UAD-2 and the upstream sequence transcription complex (USTC). Here, we demonstrate that piRNA transcription in C. elegans relies on TAF-12, a subunit of the basal transcription factor IID (TFIID). Depletion of TAF-12 reduces the production of both piRNA precursors and mature piRNAs. TAF-12 interacts with UAD-2 and facilitates piRNA focus formation in germ cell nuclei. We further show that TAF-12 triggers piRNA transcription by recruiting the RNA polymerase II subunit RPB-5, the Mediator complex subunit MDT-8, and the general transcription factors GTF-2F2 and GTF-2H2C. Thus, piRNA transcription within heterochromatic regions depends on the collaboration between histone modification readers, piRNA-specific transcription factors, and core transcription machinery. UAD-2 promotes piRNA transcription by recognizing H3K27me3 marked heterochromatin. Here the authors show that UAD-2 interacts with TAF-12, a subunit of transcription factor IID (TFIID), to drive piRNA transcription.