Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China.

BACKGROUND: Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS: In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS: 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION: The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING: Akeso Biopharma.

Broadband blue light emissions of one-dimensional hybrid Cu(I) halides with ultrahigh anti -water stability.

Low-dimensional organic-inorganic hybrid lead halide perovskites have attracted much interest in solid-state lighting and displays, but the toxicity and instability of lead halide are obstacles to their industrial applications, which must be overcome. As an alternative, Cu(I)-based hybrid metal halides have emerged as a new type of luminescent material owing to their diversified structure, adjustable luminescence, low toxicity and low cost. Herein, we report three one-dimensional (1D) hybrid Cu(I)-based halides with the general formula ACu2Br4 (A = [(Me)4-Pipz]2+ and [BuDA]2+ and [TMEDA]2+). These 1D hybrid Cu(I) halides display stable broadband blue emission with maximum emission peaks in the range of 445-474 nm and the highest photoluminescence quantum yield of 37.8%. Furthermore, in-depth experimental and theoretical investigations revealed that the broadband blue emissions originate from the radiative recombination of self-trapped excitons. Most importantly, there is no structural degradation and attenuation of emission intensity even after continuously soaking these halides in water for at least two months, demonstrating their ultra-high anti-water stability. Hirshfeld surface analysis shows that a large number of weak hydrogen bonds can protect the inorganic skeleton from degradation due to water. This work provides a new strategy for the design of water-stable Cu(I)-based halides with efficient blue emission and wide potential applications in humid environments.

Identification of quantitative trait loci for lodging and related agronomic traits in soybean (Glycine max [L.] Merr.).

BACKGROUND: Lodging, a crucial agronomic trait linked to soybean yield, poses a significant challenge in soybean production. Nevertheless, there has been less research on soybean lodging compared to other important agronomic traits, hindering progress in breeding high-yield soybeans. Our goals were to investigate lodging, pinpoint quantitative trait loci (QTL) linked to lodging, and forecast potential candidate genes linked to this trait. To achieve this, we employed a recombinant inbred line (RIL) population derived from a cross between Guizao 1 and B13 (GB) across various environments. RESULTS: The lodging score of the RIL population was found to be significantly positively correlated with flowering time, maturity time, plant height, number of main stem nodes, stem diameter, and internode length, with correlation coefficients ranging from 0.457 to 0.783. A total of 84 QTLs associated with soybean lodging and related traits were identified using the GB population. The contribution of phenotypic variance ranged from 1.26 to 66.87%, with LOD scores ranging from 2.52 to 69.22. Additionally, within these QTLs, a stable major QTL associated with lodging was newly discovered in the GB population. Out of the ten major QTLs associated with other related traits, nine of them were situated within the qLD-4-1 interval of the major lodging score locus, displaying phenotypic variations ranging from 12.10 to 66.87%. Specific alterations in gene expression were revealed through the analysis of resequencing data from the two parental lines, potentially indicating their significant roles in lodging. Subsequently, it was determined through qRT-PCR that four genes are likely to be the major genes controlling soybean lodging. CONCLUSIONS: This study's findings offer valuable insights into the genetic underpinnings of soybean lodging resistance traits. By comprehending the potential genetic factors associated with lodging, this research lays the groundwork for breeding high-yield soybeans with improved lodging resistance.

Predictive utility of emotional regulation abilities for assessing cognitive improvement in depression.

OBJECTIVE: To construct a predictive model for the improvement of cognitive function in patients with depressive disorder treated with SNRIs, based on emotional regulation abilities, and to provide personalized treatment for depressed patients. METHODS: Clinical data from 170 patients with depressive disorder treated with SNRIs at Tongji Hospital, Shanghai, from December 2017 to May 2023 were collected. Based on whether the MoCA-B total score at 3-6 months post-treatment was at least 2 points higher than at baseline, patients were divided into the cognitive function improved group (n = 80) and the cognitive function not improved group (n = 90). Stepwise logistic regression and LASSO regression were used to select predictive factors, and logistic regression analysis was applied to construct predictive models solely based on emotional regulation abilities, combined with executive functions and HAMD scores. The models were further validated through Bootstrap internal validation, calibration curve plotting, and C-index calculation, and a comparison between the two models was performed. RESULTS: An ER model with an area under the ROC curve of 0.817was established using four emotional regulation ability indicators: the valence of reappraised images, the arousal of negative images, the arousal of neutral images, and the success of reappraisal (arousal). Internal validation using Bootstrap showed a C index of 0.817, and clinical decision curves indicated that this model has a significant net benefit with a probability of improved cognitive function ranging from about 20 to 85%. Additionally, an EREH model including emotional regulation ability, executive function, and HAMD score as predictors was constructed using Lasso and logistic regression methods. This model reached an area under the ROC curve of 0.859and clinical decision curves showed high net benefits with probabilities of improved cognitive function ranging from 10 to 100%. The calibration curves of both models coincided well with the actual curves, with the latter having a higher AUC and significant statistical differences between the two models. CONCLUSION: This study suggests that emotional regulation ability may serve as a predictor for the improvement of cognitive functions in patients with depression depressive disorder treated with SNRIs. However, it is important to note that there may be other factors not covered or included in this study.The predictive model that includes executive functions and HAMD scores offers better differentiation and consistency and is more feasible in clinical practice.

A comprehensive review of traditional Chinese medicine in treating neuropathic pain.

Neuropathic pain (NP) is a common, intractable chronic pain caused by nerve dysfunction and primary lesion of the nervous system. The etiology and pathogenesis of NP have not yet been clarified, so there is a lack of precise and effective clinical treatments. In recent years, traditional Chinese medicine (TCM) has shown increasing advantages in alleviating NP. Our review aimed to define the therapeutic effect of TCM (including TCM prescriptions, TCM extracts and natural products from TCM) on NP and reveal the underlying mechanisms. Literature from 2018 to 2024 was collected from databases including Web of Science, PubMed, ScienceDirect, Google academic and CNKI databases. Herbal medicine, Traditional Chinese medicines (TCM), neuropathic pain, neuralgia and peripheral neuropathy were used as the search terms. The anti-NP activity of TCM is clarified to propose strategies for discovering active compounds against NP, and provide reference to screen anti-NP drugs from TCM. We concluded that TCM has the characteristics of multi-level, multi-component, multi-target and multi-pathway, which can alleviate NP through various pathways such as anti-inflammation, anti-oxidant, anti-apoptotic pathway, regulating autophagy, regulating intestinal flora, and influencing ion channels. Based on the experimental study and anti-NP mechanism of TCM, this paper can offer analytical evidence to support the effectiveness in treating NP. These references will be helpful to the research and development of innovative TCM with multiple levels and multiple targets. TCM can be an effective treatment for NP and can serve as a treasure house for new drug development.

Diagnosis and treatment of anterior cruciate ligament injuries: Consensus of Chinese experts part II: Graft selection and clinical outcome evaluation.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: "Graft Selection" and "Clinical Outcome Evaluation" during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive "gold standard" graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Comparative pharmacokinetic study of Anisodamine Hydrobromide tablets and injection in septic acute lung injury rats.

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection.Methods: Around 10 mmNH4Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis.Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.

[Box: see text].

Hinesol attenuates DSS-induced ulcerative colitis through the suppression of Src-mediated NF-κB and chemokine signaling pathway.

As a common inflammatory bowel disease, ulcerative colitis (UC) is featured with inflammation, oxidative damage, and the impairment of intestinal mucosal barrier, which bring threat to patients' quality of live. Hinesol, derived from Atractylodes lancea, is a unique sesquiterpenoid. Our study proposed to survey the effects and mechanism of hinesol in UC. UC mouse model was constructed using dextran sulfate sodium (DSS). Lipopolysaccharide (LPS) was applied for RAW264.7 cells stimulation to construct cell inflammatory model. The changes of disease activity index (DAI), body weight, colon length, and intestinal pathology in mice were analyzed to estimate the severity of colitis. Enzyme-linked immunosorbent assay was applied to check the changes of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase (CAT), and malondialdehyde (MDA) were estimated by corresponding reagent kit. The changes of phosphorylated (p)-NF-κB P65, and p-IκBα, ZO-1, Occludin, Claudin-1, Src, XCL1, CCL2, and CXCL16 protein were examined using western blot. Flow cytometry and cell counting kit-8 assay were utilized for assessment of cell apoptosis and viability. We found that DSS reduced mice body weight, increased DAI, shorten colon length, and led to severe enteric mucosal injury, while hinesol improved the above symptoms induced by DSS. In DSS mice, hinesol raised the levels of ZO-1, Occludin, Claudin-1, SOD, GSH-px, and CAT and decreased the levels of TNF-α, IL-18, IL-1ß, IL-6, MPO, and MDA. Additionally, in DSS mice and LPS-stimulated RAW264.7 cells, hinesol inhibited the high expression of Src, XCL1, CCL2, CXCL16, p-NF-κB P65, and p-IκBα. The molecular docking showed that there was a good interaction between hinesol and Src. Moreover, in LPS-stimulated RAW 264.7 cells, Src overexpression partially reversed the inhibition of hinesol on cell apoptosis, pro-inflammatory factors, and oxidative stress. In conclusion, hinesol alleviated DSS-induced colitis, which might have a bearing on the inhibition of Src-mediated NF-κB and chemokine signaling pathway.

Succinate dehydrogenase A deficient renal cell carcinoma: A rare renal tumor distinct from typical Succinate dehydrogenase deficient renal cell carcinoma.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of RCC classified as a molecularly defined RCC in the fifth edition of the WHO. Most gene alterations in patients with SDH-deficient RCC involve the SDHB subunit, with less involvement of the SDHC, SDHA, and SDHD subunits. Four cases of SDHA-deficient RCC have been reported in the literature, of which one case was associated with an NF2 gene mutation. Herein, we report six novel SDHA-deficient RCC cases, including two cases with NF2 gene mutations. In contrast to the typical morphology of SDH-deficient RCC, the six tumors mainly displayed glandular, sheet-like, or papillary growth patterns with prominent nucleoli (Grades 2-3), among which two cases with NF2 mutations had prominent nucleoli (Grade 3), large transparent vacuoles in the cytoplasm, and a large number of lymphocytes in the stroma. Six tumors showed negative immunohistochemical staining for SDHA and SDHB, and three cases presented with high expression of PD-L1. Second-generation sequencing revealed novel pathogenic somatic SDHA gene mutation and NF2 gene mutations in six and two tumors, respectively. Follow-up data were collected for the six patients with a follow-up time ranging from 7 to 268 months, and all six patients have survived to date. One patient received targeted therapy for tumor metastasis to the lungs after seven months, and another patient with an NF2 gene mutation received immunotherapy for lymph node metastasis revealed during surgery. SDHA-deficient RCCs with NF2 gene mutations have the ability to metastasize but might respond well to immunotherapy. For the first time, we report the largest number of SDHA-deficient RCC cases and comprehensively investigate their clinicopathological and molecular features to provide important guidance for diagnosis and clinical immunotherapy.

Hydroxysafflor yellow A exerts anti-fibrotic and anti-angiogenic effects through miR-29a-3p/PDGFRB axis in liver fibrosis.

BACKGROUND: Liver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good pharmacological activity. However, the precise mechanisms of HSYA against liver fibrosis remain unclear. PURPOSE: The objective of this study was to elucidate the impact of HSYA on liver fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo studies. METHODS: The efficacy and mechanisms of HSYA on TGF-ß1-induced HSCs and VEGFA-induced endothelial cells were investigated by MTT assay, EdU cell proliferation assay, cell scratch assay, Elisa assay, immunofluorescence assay, molecular docking, cell transfection assay, western blot analysis and RT-qPCR analysis. In CCl4-induced liver fibrosis mice model, H&E, Masson, and Sirius red staining were used to observe histopathology. Serum transaminase activity and liver biochemical indexes were tested by biochemical kit. Immunohistochemical, fluorescence in situ hybridization (FISH), western blot analysis and RT-qPCR analysis were implemented to determine the mechanism of HSYA in vivo. RESULTS: Herein, our findings confirmed that HSYA inhibited the proliferation, migration and activation of HSCs, as evidenced by a reduction in cell viability, relative migration rate, EdU staining intensity, and pro-fibrotic mRNAs and proteins expression in vitro. Mechanistically, HSYA played an anti-fibrotic and anti-angiogenic role by partially silencing PDGFRB in activated HSCs, thereby disrupting PDGFRB/MEK/ERK signal transduction and inhibiting the expression of HIF-1α, VEGFA and VEGFR2 proteins. Importantly, PDGFRB was a target gene of miR-29a-3p. Treatment with HSYA reversed the down-regulation of miR-29a-3p and antagonized PDGFRB signaling pathway in TGF-ß1-induced HSCs transfected with miR-29a-3p inhibitor. Consistent with our in vitro study, HSYA exhibited a good hepatoprotective effect in CCl4-induced liver fibrosis mice by reducing serum ALT and AST levels, decreasing the contents of four fibrosis indicators (HA, PIIIP, ColIV and LN) and hydroxyproline, and inhibiting the TGF-ß1/TGFBR signaling pathway. In terms of mechanisms, HSYA alleviated pathological angiogenesis in fibrotic liver by deactivating PDGFRB signaling pathway and impairing the positive expression of CD31. Subsequently, FISH results further corroborated HSYA affected the activation of HSCs and angiogenesis achieved by the concurrent upregulation of miR-29a-3p and downregulation of α-SMA and VEGFA. Additionally, treatment with HSYA also forged a link between HSCs and endothelial cells, as supported by inhibiting the aberrant proliferation of endothelial cells. CONCLUSION: Fundamentally, the current study has illustrated that HSYA ameliorates liver fibrosis by repressing HSCs-mediated pro-fibrotic and pro-angiogenic processes, which is contingent upon the regulatory effect of HSYA on the miR-29a-3p/PDGFRB axis. These findings provide compelling evidence bolstering the potential of HSYA as a therapeutic agent in liver fibrosis.

Four-year comparative analysis of return to sport and psychological recovery following ACL revision: Artificial ligament vs. anterior tibial tendon allograft.

Background: Research on return to sport and psychological recovery in anterior cruciate ligament (ACL) revision remains scarce. The clinical efficacy of artificial ligament in ACL revision requires further exploration. Our objectives were (1) to compare the midterm clinical outcomes of artificial ligament versus allogenic tendon graft in ACL revision and (2) to analyze the effects of employing artificial ligament on return to sport and psychological recovery in ACL revision. Methods: This cohort study included the cases receiving ACL revision from 2014 to 2021 in Sports Medicine Department of Huashan Hospital. The grafts used were Ligament Advanced Reinforcement System (LARS) and ATT allograft. We recorded patients' baseline data. The final follow-up assessment included subjective scales, physical examination, and return to sport status. We recorded the rates and timings of return to sport. Subjective scales included the 2000 International Knee Documentation Committee (IKDC) subjective score, Lysholm Knee Scaling Score (LKSS), Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Marx activity rating score, and Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI). Anterior knee stability was assessed using the KT-1000 arthrometer. Results: Fifty cases (LARS group: 27; ATT group: 23) enrolled and 45 (LARS group: 23; ATT group: 22) completed evaluations with a median follow-up period of 49 months. At recent follow-up, LARS group outperformed in knee stability (1.0 ± 1.9 mm vs. 2.6 ± 3.0 mm, P = 0.039), confidence (86.7 ± 12.4 vs. 69.4 ± 18.6, P < 0.001), emotion (82.7 ± 11.3 vs. 70.7 ± 16.2, P < 0.001), KOOS knee function (78.7 ± 8.8 vs. 69.5 ± 11.0, P = 0.003), quality of life (79.1 ± 16.1 vs. 66.4 ± 19.5, P = 0.014), Tegner score (6.3 ± 1.9 vs. 5.2 ± 2.1, P < 0.001), and Marx activity score (10.7 ± 3.7 vs. 7.9 ± 4.0, P = 0.012). The LARS group had significantly higher return rates: recreational (91.3 % vs. 63.6 %, P = 0.026), knee cutting and pivoting (87.0 % vs. 59.1 %, P = 0.035), competitive (78.3 % vs. 45.5 %, P = 0.023), and pre-injury (56.5 % vs. 27.3 %, P = 0.047). For return timings, the LARS group was earlier at recreational (11.2 ± 3.9 vs. 27.8 ± 9.0 weeks, P < 0.001), knee cutting and pivoting (17.2 ± 5.8 vs. 35.6 ± 13.8 weeks, P < 0.001), competitive (24.8 ± 16.2 vs. 53.2 ± 22.0 weeks, P < 0.001), and pre-injury levels (32.8 ± 11.0 vs. 72.8 ± 16.9 weeks, P < 0.001). Conclusion: In ACL revision, using LARS demonstrated improved joint stability and functionality compared to using allogenic ATT four years postoperative. Patients accepting the LARS procedure exhibited higher rates and earlier timings of return to various levels of sport, indicating enhanced confidence and emotional resilience. The translational potential of this article: In ACL revision, the choice of artificial ligament to shorten recovery time, thereby enabling patients to return to sport more quickly and effectively, is thought-provoking. The research value extends beyond mere graft selection, guiding future clinical trials and studies. This research enhances our understanding of the application value of artificial ligament in ACL revision, emphasizing the importance of psychological recovery and updating our perceptions of return to sport levels post-revision. It stimulates exploration into personalized rehabilitation programs and treatment strategies, aiming to optimize clinical outcomes and meet the real-world needs of patients with failed ACL reconstruction.

Synchronously in vivo real-time monitoring bacterial load and temperature with evaluating immune response to decipher bacterial infection.

Determining the precise course of bacterial infection requires abundant in vivo real-time data. Synchronous monitoring of the bacterial load, temperature, and immune response can satisfy the shortage of real-time in vivo data. Here, we conducted a study in the joint-infected mouse model to synchronously monitor the bacterial load, temperature, and immune response using the second near-infrared (NIR-II) fluorescence imaging, infrared thermography, and immune response analysis for 2 weeks. Staphylococcus aureus (S. aureus) was proved successfully labeled with glucose-conjugated quantum dots in vitro and in subcutaneous-infected model. The bacterial load indicated by NIR-II fluorescence imaging underwent a sharp drop at 1 day postinfection. At the same time, the temperature gap detected through infrared thermography synchronously brought by infection reached lowest value. Meanwhile, the flow cytometry analysis demonstrated that immune response including macrophage, neutrophil, B lymphocyte, and T lymphocyte increased to the peak at 1 day postinfection. Moreover, both M1 macrophage and M2 macrophage in the blood have an obvious change at ~ 1 day postinfection, and the change was opposite. In summary, this study not only obtained real-time and long-time in vivo data on the bacterial load, temperature gap, and immune response in the mice model of S. aureus infection, but also found that 1 day postinfection was the key time point during immune response against S. aureus infection. Our study will contribute to synchronously and precisely studying the complicated complex dynamic relationship after bacterial infection at the animal level.

Application progress of latent class growth models in dynamic prevention and control strategies for acquired immunodeficiency syndrome. / æ½œåˆ†ç±»å¢žé•¿æ¨¡åž‹åœ¨èŽ·å¾—æ€§å ç–«ç¼ºé™·ç»¼åˆå¾åŠ¨æ€é˜²æŽ§ç­–ç•¥ä¸­çš„åº”ç”¨è¿›å±•.

The prevention and control requirements for HIV/AIDS vary significantly among different populations, posing substantial challenges to the formulation and implementation of intervention strategies. Dynamically assessing the heterogeneity and disease progression trajectories of various groups is crucial. Latent class growth model (LCGM) serves as a statistical approach that fits a longitudinal data into N subgroups of individual development trajectories, identifying and analyzing the progression paths of different subgroups, thereby offering a novel perspective for disease control strategies. LCGM has shown significant advantages in the application of HIV/AIDS prevention and control, especially in gaining a deeper understanding and analysis of epidemiological characteristics, risk behaviors, psychological research, heterogeneity in testing, and dynamic changes. Summarizing the advantages and limitations of applying LCGM can provide a reliable basis for precise prevention and control of HIV/AIDS.

Spontaneously ruptured huge hepatic subcapsular hematoma associated with preeclampsia: A case report and literature review.

Hepatic subcapsular hematoma (HSH) is an uncommon complication of pregnancy and is associated with elevated rates of maternal and foetal mortality. The rupture of an HSH is a critical situation that necessitates immediate and timely intervention to prevent loss of life. We present here, a case of a spontaneously ruptured massive HSH caused by preeclampsia. In addition, we conducted a comprehensive review of existing literature, encompassing 49 cases of HSH associated with pregnancy. If a pregnant woman with gestational hypertension experiences right upper abdominal pain with shoulder pain or radiating shoulder pain, it is crucial for her to have an urgent abdominal ultrasound because of the potential development of HSH and/or rupture. Our review of current literature suggests that opting for a caesarean section may offer notable advantages in preventing HSH rupture.

Engineering Yeast Peroxisomes for α-Bisabolene Production from Sole Methanol with the Aid of Proteomic Analysis.

Microbial metabolic engineering provides a feasible approach to sustainably produce advanced biofuels and biochemicals from renewable feedstocks. Methanol is an ideal feedstock since it can be massively produced from CO2 through green energy, such as solar energy. However, engineering microbes to transform methanol and overproduce chemicals is challenging. Notably, the microbial production of isoprenoids from methanol is still rarely reported. Here, we extensively engineered Pichia pastoris (syn. Komagataella phaffii) for the overproduction of sesquiterpene α-bisabolene from sole methanol by optimizing the mevalonate pathway and peroxisomal compartmentalization. Furthermore, through label-free quantification (LFQ) proteomic analysis of the engineered strains, we identified the key bottlenecks in the peroxisomal targeting pathway, and overexpressing the limiting enzyme EfmvaE significantly improved α-bisabolene production to 212 mg/L with the peroxisomal pathway. The engineered strain LH122 with the optimized peroxisomal pathway produced 1.1 g/L α-bisabolene under fed-batch fermentation in shake flasks, achieving a 69% increase over that of the cytosolic pathway. This study provides a viable approach for overproducing isoprenoid from sole methanol in engineered yeast cell factories and shows that proteomic analysis can help optimize the organelle compartmentalized pathways to enhance chemical production.

Corrigendum: Effects of essential oil extracted from Artemisia argyi leaf on lipid metabolism and gut microbiota in high-fat diet-fed mice.

[This corrects the article DOI: 10.3389/fnut.2022.1024722.].

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Effects of BBIBP-CorV vaccine on gut microbiota and short-chain fatty acids in mice exposed to bis (2-ethylhexyl) phthalate and dioctyl terephthalate.

As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.

Exploring the Anticancer Properties of Sakuranin Flavanone in Human Oropharyngeal Squamous Carcinoma Cells by Studying Its Effects on Caspase-driven Apoptosis, Mitochondrial Membrane Potential (MMP) Loss, Cell Migratory and Invasiveness and m-TOR/PI3K/AKT Signalling Pathway.

Sakuranin is a flavanone which is a class of flavonoids found abundantly in Prunus species. Flavonoids have been long known for their anticancer properties against a range of human cancers. However, there are no previous reports on the anticancer effects of sakuranin flavanone molecule. This study was designed to study the anticancer effects of sakuranin against human oropharyngeal carcinoma cells along with investigating its effects on caspase-mediated apoptosis, mitochondrial membrane potential (MMP) loss, cell migration and invasion and m-TOR/PI3K/AKT signalling pathway. MTT assay was used to study effects on cell viability. The apoptotic studies were carried out through AO/EB staining, annexin V/FITC staining, comet assay and western blotting assay. Transwell chambers assay was used to study effects on cell migration and invasion. Flow cytometry was used to study effects of Sakuranin on mitochondrial membrane potential loss (MMP). Finally, western blotting was used to investigate m-TOR/PI3K/AKT signalling pathway. Results indicated that Sakuranin led to potent cell proliferation inhibition in a dose-dependent manner. Sakuranin also induced apoptotic cell death as indicated by fluorescence microscopy and annexin V/FITC staining assays. The apoptotic induction was mediated via activation of caspase-3, caspase-9, and Bax while as it led to downregulation of Bcl-2. Sakuranin also caused inhibition of cell migration and cell invasion along with causing significant decrease in MMP. Sakuranin also caused inhibition of expressions of proteins related with m-TOR/PI3K/AKT signalling pathway. In conclusion, the current findings clearly indicate anticancer effects of Sakuranin flavanone in human oropharyngeal cancer cells and are mediated via caspase activated apoptosis, inhibition of cell migration and invasion, loss of mitochondrial membrane potential and targeting m-TOR/PI3K/AKT signalling pathway.