Stretchable Electrodes with Interfacial Percolation Network.

Stretchable electrodes are an essential component that determines the functionality and reliability of stretchable electronics, but face the challenge of balancing conductivity and stretchability. This work proposes a new conducting concept called the interfacial percolation network (PN) that results in stretchable electrodes with high conductivity, large stretchability, and high stability. The interfacial PN is composed of a 2D silver nanowires (AgNWs) PN and a protruding 3D AgNWs PN embedded on the surface and in the near-surface region of an elastic polymer matrix, respectively. The protruded PN is obtained by changing the arrangements of AgNWs from horizontal to quasi-vertical through introducing foreign polymer domains in the near-surface region of the polymer matrix. The resulting electrode achieves a conductivity of 13 500 S cm-1 and a stretchability of 660%. Its resistance changes under stretched conditions are orders of magnitude lower than those of conventional 2D PN and 2D + 3D PN. An interfacial PN electrode made from liquid metal remained its conductivity at 46 750 S cm-1 after the electrode underwent multiple stretch-release cycles with a deformation of >600%. The concept of interfacial PN provides fruitful implications for the design of stretchable electronics.

Fully Biodegradable Packaging Films for Fresh Food Storage Based on Oil-Infused Bacterial Cellulose.

Fully biodegradable packaging materials are demanded to resolve the issue of plastic pollution. However, the fresh food storage performance of biodegradable materials is generally much lower than that of plastics due to their high permeability, microbial friendliness, and limited stretchability and transparency. Here a biodegradable packaging material is reported with high fresh food storage performance based on an oil-infused bacterial cellulose (OBC) porous film. The oil infusion significantly improved cellulose's food-keeping performance by reducing its gas permeability, increasing its stretchability and transparency, and enabling the active release of green vapor-phase preservative molecules, while maintaining its intrinsically high degradability. Strawberries stored in a container with the OBC lid at 23 °C after 5 days exhibited a moldy rate of 0%, in contrast to the 100% moldy rate of those stored by poly(ethylene). Enhanced storage performance is also obtained on tomatoes, pork, and shrimp. The OBC film is naturally degraded after being buried in wet soil at 30 °C for 9 days, identical to the degradation rate of bacterial cellulose. The liquid seal strategy broadly applies to different celluloses, providing a general option for developing cellulose-based biodegradable packaging materials.

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles.

Although preclinical and clinical studies have shown that exercise can inhibit bone metastasis progression, the mechanism remains poorly understood. Here, we found that non-small cell lung cancer (NSCLC) cells adjacent to bone tissue had a much lower proliferative capacity than the surrounding tumor cells in patients and mice. Subsequently, it was demonstrated that osteocytes, sensing mechanical stimulation generated by exercise, inhibit NSCLC cell proliferation and sustain the dormancy thereof by releasing small extracellular vesicles with tumor suppressor micro-RNAs, such as miR-99b-3p. Furthermore, we evaluated the effects of mechanical loading and treadmill exercise on the bone metastasis progression of NSCLC in mice. As expected, mechanical loading of the tibia inhibited the bone metastasis progression of NSCLC. Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise-afforded protection against bone metastasis progression.

Structural and interfacial properties of acetylated Millettia speciosa Champ polysaccharide and stability evaluation of the resultant O/W emulsion containing ß-carotene.

The aim of this study was to investigate the effects of acetylation modification on the structural, interfacial and emulsifying properties of Millettia speciosa Champ polysaccharide (MSCP). Besides, the influence of acetylation modification on the encapsulation properties of polysaccharide-based emulsion was also explored. Results indicated that modification resulted in a prominent reduction in molecular weight of MSCP and the interfacial layer thickness formed by acetylated MSCP (AC-MSCP) was also decreased, but the adsorption rate and ability of AC-MSCP to reduce interfacial tension were improved. AC-MSCP formulated emulsion possessed smaller droplet size (6.8 µm) and exhibited better physical stability under stressful conditions. The chemical stability of ß-carotene was also profoundly enhanced by AC-MSCP fabricated emulsion. Moreover, AC-MSCP improved lipids digestion extent, thus facilitating the formation of micelle and increasing bioaccessibility of ß-carotene. This study provided insights for rational modification of polysaccharide-based emulsifier and designing delivery system for chemically labile hydrophobic bioactive components.

A gut microbial signature for combination immune checkpoint blockade across cancer types.

Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is a relationship between a cancer patient's gut microbiota composition and clinical response to ICB; however, defining microbiome-based biomarkers that generalize across cohorts has been challenging. This may relate to previous efforts quantifying microbiota to species (or higher taxonomic rank) abundances, whereas microbial functions are often strain specific. Here, we performed deep shotgun metagenomic sequencing of baseline fecal samples from a unique, richly annotated phase 2 trial cohort of patients with diverse rare cancers treated with combination ICB (n = 106 discovery cohort). We demonstrate that strain-resolved microbial abundances improve machine learning predictions of ICB response and 12-month progression-free survival relative to models built using species-rank quantifications or comprehensive pretreatment clinical factors. Through a meta-analysis of gut metagenomes from a further six comparable studies (n = 364 validation cohort), we found cross-cancer (and cross-country) validity of strain-response signatures, but only when the training and test cohorts used concordant ICB regimens (anti-PD-1 monotherapy or combination anti-PD-1 plus anti-CTLA-4). This suggests that future development of gut microbiome diagnostics or therapeutics should be tailored according to ICB treatment regimen rather than according to cancer type.

Epidemiology and distribution of cruciate ligament injuries in children and adolescents, with an analysis of risk factors for concomitant meniscal tear.

Introduction: To investigate the epidemiological features and prevalence of cruciate ligament injuries (CLI) in children and adolescents, and to examine the potential risk factors associated with concomitant meniscal tear (MT) among this population. Methods: The demographic data and injury details of children and adolescents with CLI from Southeast China were analyzed to describe their distribution characteristics, alongside an analysis of the prevalence of MTs, the most frequent complication. In addition, binary logistic analysis was employed to ascertain the risk factors linked to MT in individuals suffering from CLI. Results: A total of 203 patients with CLI (n = 206) met the inclusion criteria, with a male-to-female ratio of 2.3:1. Notably, a higher proportion of females were aged ≤16 years old compared to males, who predominated in patients aged >16 years (P = 0.001). Among children and adolescents, anterior cruciate ligament (ACL) injuries were the primary type of CLI, accounting for 88.18% (179/203) of all cases. The majority of cases (132/203, 65.02%) were sustained during sports activities, and sprains were the predominant mechanism of injury (176/203, 86.7%). Additionally, the most common associated injury was an MT (157/203, 77.34%). The posterior horn is the most frequently affected site for both medial MT (62.93% out of 73 cases) and lateral MT (70.19% out of 73 cases). Moreover, vertical tears constituted the majority of medial MTs (59.48% out of 116 cases). Furthermore, patients with a higher BMI faced an increased risk of associated MT in comparison to non-overweight patients (88% vs. 73.86%; P = 0.038). Each increase in BMI unit was linked with a 14% higher probability of associated MT occurrence in children and adolescents with CLI (OR = 1.140; P = 0.036). Discussion: ACL injuries are a common form of knee ligament injury among children and adolescents, especially those over the age of 16, and are often the result of a sprain. Meniscal posterior horn injury is the most commonly associated injury of youth with CLI. Additionally, overweight or obese people with CLI are at a greater risk of developing MT.

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing.

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

MIR222HG/LIN28B/ATG5 Axis Drives M2 Macrophage Polarization and Proliferation of Hepatocellular Carcinoma Cells.

Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of hepatocellular carcinoma (HCC). This study aimed to investigate the potential of MIR222HG in HCC. HCC cells were co-cultured with U937 cells. Gene expression was determined using reverse transcription-quantitative (RT-q) PCR and western blot. Functional analysis was performed using Cell Counting Kit 8 (CCK-8), colony formation, and flow cytometry assays. We found that MIR222HG was overexpressed in HCC patients as well as HepG2 and Huh7 cells. MIR222HG-mediated upregulation of autophagy related 5 (ATG5) promoted tumor cell autophagy and the activation of M2-like tumor-associated macrophages (TAM2). Moreover, MIR222HG-mediated the activation of TAM2 drove the proliferation of HCC cells. Additionally, MIR222HG increased the mRNA expression as well as promoted the mRNA stability of ATG5 via binding to lin-28 homolog B (LIN28B). In conclusion, MIR222HG-mediated autophagy and the activation of TAM2 promote the aggressiveness of HCC cells via regulating LIN28B/ATG5 signaling.

Improvement of Prediction Performance for Radiation Pneumonitis by Using 3-Dimensional Dosiomic Features.

INTRODUCTION: Patients with early non-small-cell lung cancer (NSCLC) have a relatively long survival time after stereotactic body radiation therapy (SBRT). Predicting radiation-induced pneumonia (RP) has important clinical and social implications for improving the quality of life of such patients. This study developed an RP prediction model by using 3-dimensional (3D) dosiomic features. The model can be used to guide radiation therapy to reduce toxicity. METHODS: Radiomic features were extracted from pre-treatment CT, dose-volume histogram (DVH) parameters and dosiomic features were extracted from the 3D dose distribution of 140 lung cancer patients. Four predictive models: (1) CT; (2) CT + DVH; (3) CT + Rtdose; and (4) Hybrid, CT + DVH + Rtdose, were trained to predict symptomatic RP by extremely randomized trees. Accuracy, sensitivity, specificity, and area under the receiver operator characteristic curve were evaluated. RESULT: Results showed that the fraction regimen was correlated with symptomatic RP (P < .001). The proposed model achieved promising prediction results. The performance metrics for CT, CT + DVH, CT + Rtdose, and Hybrid were as follows: accuracy: 0.786, 0.821, 0.821, and 0.857; sensitivity: 0.625, 1, 0.875, and 1; specificity: 0.8, 0.565, 0.5, and 0.875; and area under the receiver operator characteristic curve: 0.791, 0.809, 0.907, and 0.920, respectively. CONCLUSION: Dosiomic features can improve the performance of the predictive model for symptomatic RP compared with that obtained with the CT + DVH model. The model proposed in this study can help radiation oncologists individually predict the incidence rate of RP.

[Clinical Analysis of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Children].

OBJECTIVE: To explore the clinical characteristics, molecular characteristics, treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) with a therapeutic target. METHODS: A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021. The data of age, gender, white blood cell (WBC) count at initial diagnosis, genetic characteristics, molecular biological changes, chemotherapy regimen, different targeted drugs were given, and minimal residual disease (MRD) on day 19, MRD on day 46, whether hematopoietic stem cell transplantation (HSCT) were retrospective analyed, and the clinical characteristics and treatment effect were summarized. Survival analysis was performed by Kaplan-Meier method. RESULTS: The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients, 10 patients were treated with targeted drugs during treatment, and 3 patients were bridged with HSCT, 1 patient died and 2 patients survived. Among the 24 patients who did not receive HSCT, 1 patient developed relapse, and achieved complete remission (CR) after treatment with chimeric antigen receptors T cells (CAR-T). The 3-year overall survival, 3-year relapse-free survival and 3-year event-free survival rate of 27 patients were (95.5±4.4)%, (95.0±4.9)% and (90.7±6.3)% respectively. CONCLUSION: Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children, combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor, and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.

Dosimetry and treatment efficiency of SBRT using TaiChiB radiotherapy system for two-lung lesions with one overlapping organs at risk.

Purpose: This study aims to assess the dosimetry and treatment efficiency of TaiChiB-based Stereotactic Body Radiotherapy (SBRT) plans applying to treat two-lung lesions with one overlapping organs at risk. Methods: For four retrospective patients diagnosed with two-lung lesions each patient, four treatment plans were designed including Plan Edge, TaiChiB linac-based, RGS-based, and a linac-RGS hybrid (Plan TCLinac, Plan TCRGS, and Plan TCHybrid). Dosimetric metrics and beam-on time were employed to evaluate and compare the TaiChiB-based plans against Plan Edge. Results: For Conformity Index (CI), Plan TCRGS outperformed all other plans with an average CI of 1.06, as opposed to Plan Edge's 1.33. Similarly, for R50 %, Plan TCRGS was superior with an average R50 % of 3.79, better than Plan Edge's 4.28. In terms of D2 cm, Plan TCRGS also led with an average of 48.48%, compared to Plan Edge's 56.25%. For organ at risk (OAR) sparing, Plan TCRGS often displayed the lowest dosimetric values, notably for the spinal cord (Dmax 5.92 Gy) and lungs (D1500cc 1.00 Gy, D1000cc 2.61 Gy, V10 Gy 15.14%). However, its high Dmax values for the heart and great vessels sometimes exceeded safety thresholds. Plan TCHybrid presented a balanced approach, showing doses comparable to or better than Plan Edge without crossing safety limits. In terms of beam-on time, Plan TCLinac emerged as the most efficient treatment option in three out of four cases, followed closely by Plan Edge in one case. Plan TCRGS, despite its dosimetric advantages, was the least efficient, recording notably longer beam-on times, with a peak at 33.28 minutes in Case 2. Conclusion: For patients with two-lung lesions treated by SBRT whose one lesion overlaps with OARs, the Plan TCHybrid delivered by TaiChiB digital radiotherapy system can be recommended as a clinical option.

Observation of a Bone Invasion Model of Aspergillus fumigatus In Vitro and Analysis of the Antifungal Susceptibility.

BACKGROUND: Recently, the prevalence of invasive fungal infections has been on the rise, and one of the prevalent symptoms frequently observed is bone deterioration and bone loss. MATERIALS AND METHODS: Using an in vitro model we studied how Aspergillus fumigatus invades the bone. Pathological analysis was then employed to observe the structure and distinctive features of the invading fungal elements within the bone invasion model. Meanwhile, the antifungal effects of itraconazole, voriconazole, posaconazole, and amphotericin B were evaluated. RESULTS: The pathological findings showed that in the experimental group, fungal spores and hyphae invaded the bone tissue or were observed growing in the vicinity of the bone edge tissues, as indicated by both HE and PAS staining. In contrast, no fungal elements were observed in the control group, indicating that the in vitro bone invasion model of A. fumigatus was successfully constructed. Furthermore, the findings from the antifungal sensitivity test demonstrated that the lowest effective concentrations of antifungal drugs against the bone invasion model were as follows: 4 µg/ml for itraconazole, 0.5 µg/ml for voriconazole, 2 µg/ml for posaconazole, and 2 µg/ml for amphotericin B. DISCUSSION: The successful construction of the bone invasion model of A. fumigatus has provided a solid basis for future investigations into the mechanisms underlying A. fumigatus bone invasion and the study of its virulence factors. Utilizing bone models is of utmost importance in advancing the development of novel antifungal treatment approaches, as well as in effectively preventing and treating fungal bone invasion and osteolytic diseases.

Optimizing rice grain size by attenuating phosphorylation-triggered functional impairment of a chromatin modifier ternary complex.

Histone acetylation affects numerous cellular processes, such as gene transcription, in both plants and animals. However, the posttranslational modification-participated regulatory networks for crop-yield-related traits are largely unexplored. Here, we characterize a regulatory axis for controlling rice grain size and yield, centered on a potent histone acetyltransferase (chromatin modifier) known as HHC4. HHC4 interacts with and forms a ternary complex with adaptor protein ADA2 and transcription factor bZIP23, wherein bZIP23 recruits HHC4 to specific promoters, and ADA2 and HHC4 additively enhance bZIP23 transactivation on target genes. Meanwhile, HHC4 interacts with and is phosphorylated by GSK3-like kinase TGW3. The resultant phosphorylation triggers several functional impairments of the HHC4 ternary complex. In addition, we identify two major phosphorylation sites of HHC4 by TGW3-sites which play an important role in controlling rice grain size. Overall, our findings thus have critical implications for understanding epigenetic basis of grain size control and manipulating the knowledge for higher crop productivity.

Emulsifiable oil-formulated Beauveria bassiana competes with imidacloprid for seasonal control of cereal aphids in Zhejiang, China.

BACKGROUND: Alternatives to neonicotinoids against cereal aphids are needed to mitigate aphid resistance and non-target effects. The emulsifiable oil formulations of two Beauveria bassiana strains, namely Bb registered as a mycoinsecticide and TBb overexpressing an endogenous virulence factor, were tested for seasonal control of cereal aphids at the elongating (April 7) to milk ripening (May 12) stages of winter wheat crop in Yuhang, Zhejiang. Each of three field trials consisted of blank control and the treatments (three randomized 100-m2 plots per capita) of each fungal strain sprayed biweekly at rates of 1.0 × 1013 and 1.5 × 1013 conidia ha-1 and 10% imidacloprid WP sprayed biweekly at a label rate. RESULTS: Tiller infestation percentage and aphid density in the 5-week field trials after the first spray were reduced to 18.7-22.4% and 9.1-12.4 aphids per tiller in the fungal treatments, and 12.8-25.3% and 2.8-20.9 aphids per tiller in the chemical treatment, contrasting with 49.2-60.3% and 37.1-108.5 aphids per tiller in the control. Percent control efficacies (±SD) computed with weekly aphid densities over the period averaged 84.0 ± 1.6 and 85.3 ± 1.8 versus 78.0 ± 4.0 and 79.9 ± 3.2 in the high-rate versus low-rate treatments of Bb and TBb, respectively, and 84.5 ± 7.8 in the chemical treatment. Imidacloprid showed faster kill action but more variable efficacy than the fungal treatments throughout the trials. CONCLUSION: Either Bb or TBb formulation competes with imidacloprid in reducing percent infestation and aphid density. The overall efficacy was significantly higher in the treatments of TBb than of Bb. © 2024 Society of Chemical Industry.

The response pattern of the microbial community structure and metabolic profile of jiupei to Bacillus subtilis JP1 addition during baijiu fermentation.

BACKGROUND: Baijiu brewing is a complex and multifaceted multimicrobial co-fermentation process, in which various microorganisms interact to form an interdependent micro-ecosystem, subsequently influencing metabolic activities and compound production. Among these microorganisms, Bacillus, an important bacterial genus in the liquor brewing process, remains unclear in its role in shaping the brewing microbial community and its functional metabolism. RESULTS: A baijiu fermentation system was constructed using B. subtilis JP1 isolated from native jiupei (grain mixture) combined with daqu (a saccharifying agent) and huangshui (a fermentation byproduct). Based on high-throughput amplicon sequencing analysis, it was evident that B. subtilis JP1 significantly influences bacterial microbial diversity and fungal community structure in baijiu fermentation. Of these, Aspergillus and Monascus emerge as the most markedly altered microbial genera in the jiupei community. Based on co-occurrence networks and bidirectional orthogonal partial least squares discriminant analysis models, it was demonstrated that the addition of B. subtilis JP1 intensified microbial interactions in jiupei fermentation, consequently enhancing the production of volatile flavor compounds such as heptanoic acid, butyl hexanoate and 3-methylthiopropanol in jiupei. CONCLUSION: B. subtilis JP1 significantly alters the microbial community structure of jiupei, enhancing aroma formation during fermentation. These findings will contribute to a broader application in solid-state fermentation. © 2024 Society of Chemical Industry.

Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.

Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .