Perioperative outcomes of transvaginal specimen extraction laparoscopic total gastrectomy and conventional laparoscopic-assisted total gastrectomy.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has emerged as a promising alternative compared to conventional laparoscopic-assisted total gastrectomy (LATG) for treating gastric cancer (GC). However, evidence regarding the efficacy and safety of NOSES for GC surgery is limited. This study aimed to compare the safety and feasibility, in addition to postoperative complications of NOSES and LATG. AIM: To discuss the postoperative effects of two different surgical methods in patients with GC. METHODS: Dual circular staplers were used in Roux-en-Y digestive tract reconstruction for transvaginal specimen extraction LATG, and its outcomes were compared with LATG in a cohort of 51 GC patients with tumor size ≤ 5 cm. The study was conducted from May 2018 to September 2020, and patients were categorized into the NOSES group (n = 22) and LATG group (n = 29). Perioperative parameters were compared and analyzed, including patient and tumor characteristics, postoperative outcomes, and anastomosis-related complications, postoperative hospital stay, the length of abdominal incision, difference in tumor type, postoperative complications, and postoperative survival. RESULTS: Postoperative exhaust time, operation duration, mean postoperative hospital stay, length of abdominal incision, number of specific staplers used, and Brief Illness Perception Questionnaire score were significant in both groups (P < 0.01). In the NOSES group, the postoperative time to first flatus, mean postoperative hospital stay, and length of abdominal incision were significantly shorter than those in the LATG group. Patients in the NOSES group had faster postoperative recovery, and achieved abdominal minimally invasive incision that met aesthetic requirements. There were no significant differences in gender, age, tumor type, postoperative complications, and postoperative survival between the two groups. CONCLUSION: The application of dual circular staplers in Roux-en-Y digestive tract reconstruction combined with NOSES gastrectomy is safe and convenient. This approach offers better short-term outcomes compared to LATG, while long-term survival rates are comparable to those of conventional laparoscopic surgery.

Safety and efficacy of tract embolization using gelatin sponge particles in reducing pneumothorax after CT-guided percutaneous lung biopsy in patients with emphysema.

BACKGROUND: The incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined. METHODS: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement. RESULTS: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema. CONCLUSIONS: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement. TRIAL REGISTRATION: Retrospectively registered.

Role of hydrogen sulfide in dermatological diseases.

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.

Imaging performance prediction of a hypersonic target in a geosynchronous orbit based on multi-dimensional information correlation of radiation, multi-spectral, and polarization.

Hypersonic target detection based on infrared intensity characteristics is easily disturbed by sea surface and cloud flares when detected by space-based optical systems, which results in a low detection rate, high false alarm, and difficulty in stable detection. This paper explores a method to improve target detection performance based on the correlation of infrared radiation, multi-spectral and polarization. Firstly, the comprehensive factors that influence complex ambient illumination, atmospheric transmission, and clutter background on spectral-polarization characteristics of hypersonic targets are analyzed. Based on the global radiation scattering theory, the temperature distribution model of the hypersonic target is established by using FLUENT. The polarization emission and pBRDF model of the target is established, and the radiation polarization transfer model is generated. Secondly, the sea surface temperature distribution is obtained by inversion of Landsat8 remote sensing data. The radiation polarization transfer model of the sea surface is established based on the Cox-Munk model combined with pBRDF and the polarization emission model. Thirdly, the polarization scattering effect of atmospheric particles on the upward radiation of the interaction of the target with the sunlight is considered comprehensively, and the 6SV radiative transfer model is used to calculate the polarization effect of atmospheric particles on the upward radiation transmission of the target and the background. Then, combined with the point diffusion of the optical system and the photoelectric conversion of the detector, the multi-dimensional full-chain imaging prediction model of the hypersonic target-sea background-ambient atmosphere-optical system-detector is established. The imaging characteristics and detection performance of the target in different imaging dimensions are simulated and analyzed with the signal-to-clutter ratio (SCR). The research shows that in the direction of reflected sunlight from the sea surface, the sea surface glare is suppressed and the target is highlighted through a target detection method of multi-dimensional information. This method has better detection results than the infrared multi-spectral detection method.

Activation of kappa opioid receptor suppresses post-traumatic osteoarthritis via sequestering STAT3 on the plasma membrane.

OBJECTIVE: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. METHODS: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). RESULTS: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1ß and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. CONCLUSIONS: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA.

Feasibility study of use of desflurane combined with dexmedetomidine in inhibiting postoperative neurocognitive disorders in elderly patients under general anesthesia: A perspective study.

This study aimed to explore whether the combined application of desflurane and dexmedetomidine (Dex) reduces the occurrence of postoperative neurocognitive disorders (PND) in patients. We selected patients in our hospital who underwent surgery under general anesthesia, and divided them into two groups: Dex and desflurane (Dex + Des) and desflurane (Des) groups. The data of patients were collected and the Mini-Mental State Examination (MMSE) score was used to assess cognitive status. The blood cell counts were determined preoperatively and on postoperative days 1, 3, and 6, and the percentage of neutrophils and lymphocytes were also recorded. The statistical methods used were the independent-samples t-test and the χ 2 test. Pearson's correlation was used to analyze the correlation between PND and inflammation. The incidence of PND in the Dex + Des group was lower than that in the Des group. The postoperative MMSE scores in the Dex + Des group were higher than those in the Des group (p = 0.032). The percentage of neutrophils in the Dex + Des group was significantly lower than that in the Des group on the first and third days after surgery (p = 0.007; p = 0.028). The MMSE scores on the first day after surgery were negatively correlated with the multiple changes in white blood counts and the percentage of neutrophils (r = -0.3038 and -0.3330). Dex combined with Des reduced the incidence of PND and reduced the postoperative inflammatory cell counts.

ErbB3 is required for hyperaminoacidemia-induced pancreatic α cell hyperplasia.

Blood amino acid levels are maintained in a narrow physiological range. The pancreatic α cells have emerged as the primary aminoacidemia regulator through glucagon secretion to promote hepatic amino acid catabolism. Interruption of glucagon signaling disrupts the liver - α cells axis leading to hyperaminoacidemia, which triggers a compensatory rise in glucagon secretion and α cell hyperplasia. The mechanisms of hyperaminoacidemia-induced α cell hyperplasia remain incompletely understood. Using a mouse α cell line and in vivo studies in zebrafish and mice, we found that hyperaminoacidemia-induced α cell hyperplasia requires ErbB3 signaling. In addition to mTORC1, another ErbB3 downstream effector STAT3 also plays a role in α cell hyperplasia. Mechanistically, ErbB3 may partner with ErbB2 to stimulate cyclin D2 and suppress p27 via mTORC1 and STAT3. Our study identifies ErbB3 as a new regulator for hyperaminoacidemia-induced α cell proliferation and a critical component of the liver-α cells axis that regulates aminoacidemia.

Machine learning-assisted MALDI-TOF MS toward rapid classification of milk products.

This study established a method for rapid classification of milk products by combining matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis with machine learning techniques. The analysis of 2 different types of milk products was used as an example. To select key variables as potential markers, integrated machine learning strategies based on 6 feature selection techniques combined with support vector machine (SVM) classifier were implemented to screen the informative features and classify the milk samples. The models were evaluated and compared by accuracy, Akaike information criterion (AIC), and Bayesian information criterion (BIC). The results showed the least absolute shrinkage and selection operator (LASSO) combined with SVM performs best, with prediction accuracy of 100 ± 0%, AIC of -360 ± 22, and BIC of -345 ± 22. Six features were selected by LASSO and identified based on the available protein molecular mass data. These results indicate that MALDI-TOF MS coupled with machine learning technique could be used to search for potential key targets for authentication and quality control of food products.

Association of plasma lactoferrin levels with disease severity in glaucoma patients.

Objective: To explore the relationship between plasma lactoferrin (Lf) and glaucoma, assessing the clinical utility of Lf in glaucoma. Methods: A cross-sectional study involved 161 glaucoma patients and 115 healthy controls, with a follow-up of 14 subjects after approximately 2 years. Plasma Lf markers were quantified using ELISA, comparing levels between glaucoma patients and healthy controls, and analyzing plasma Lf across different glaucoma severity grades. Results: Glaucoma patients had significantly elevated plasma Lf levels compared to healthy controls (p < 0.001). Higher plasma Lf levels correlated with more severe disease stages (HPA grades showed ρ = 0.435, p < 0.001; AGIS grades showed ρ = 0.436, p < 0.001) and reduced retinal nerve fiber layer (RNFL) thickness (RNFL thickness showed ρ = -0.204, p = 0.024). ROC curve analysis demonstrated the efficacy of glaucoma markers in differentiating early-stage from advanced glaucoma. Conclusion: Plasma Lf levels are significantly associated with glaucoma severity and may be involved in the pathogenic progression of the disease.

[Effect of Fallow on Nitrogen Accumulation in Soil Profile and Shallow Groundwater in Cropland Around Fuxian Lake].

Soil nitrogen accumulation in cropland and groundwater nitrogen pollution can be effectively alleviated by reducing exogenous nitrogen input, and fallow is an important measure for reducing exogenous nitrogen input. To explore the effects of fallow on nitrogen accumulation in the soil profile and shallow groundwater, the soil profile and shallow groundwater in cropland around Fuxian Lake were selected as research objects. The changes in nitrogen accumulation in the 0-100 cm soil profile and nitrogen concentration in shallow groundwater before (December 2017) and after (August 2020 and April 2021) fallow and their relationships were analyzed. The results showed that the content and storage of nitrogen in soil profiles were significantly reduced by fallow, and the contents of TN, ON, DTN, NO3--N, and NH4+-N in 0-30, 30-60, and 60-100 cm soil profiles after fallow decreased by 18.4 %-36.5 %, 16.1 %-26.8 %, 54.0 %-130.2 %, 59.5 %-90.8 %, and 60.1 %-110.6 %, respectively. The storages of TN, ON, DTN, NO3--N, and NH4+-N in 0-100 cm soil profiles before fallow were (17.20 ±0.97) t·hm-2, (15.50 ±1.23) t·hm-2, (0.68 ±0.06) t·hm-2, (266.8 ±31.17) kg·hm-2, and (18.7 ±3.04) kg·hm-2, respectively. However, their storages after fallow decreased by 25.5 %, 23.3 %, 44.7 %, 80.1 %, and 59.9 %, respectively. Fallow also changed the concentration and composition of different forms of nitrogen in shallow groundwater. The concentrations of TN, ON, NO3--N, and NH4+-N in groundwater after fallow decreased by 88.4 %, 82.7 %, 92.1 %, and 65.8 %, respectively, and ON/TN and NH4+-N/TN increased from 26 % and 6 % before fallow to 39 % and 17 % after fallow, respectively, whereas NO3--N/TN decreased from 61 % before fallow to 41 % after fallow. Changes in nitrogen concentrations and their forms in groundwater were closely related to DTN, NO3--N, and NH4+-N in the soil profile and pH, ORP, and DO in groundwater before and after fallow. Our study highlights that fallow effectively reduced nitrogen accumulation in cropland soil profiles, further alleviating nitrogen pollution in shallow groundwater, and was conducive to preventing the deterioration of water quality in plateau lakes.

[Preparation of monoclonal antibodies against the envelope protein extracellular domain of Zika virus in mice].

Objective To prepare monoclonal antibodies against the envelope protein extracellular domain (Eecto) of Zika virus (ZIKV) in mice. Methods A prokaryotic expression plasmid, pET28a-ZIKV-Eecto of ZIKV Eecto, was constructed, transformed into Escherichia coli BL21 and induced by isopropyl ß-D-thiogalactoside (IPTG). The recombinant Eecto protein was expressed in the form of inclusion bodies, and purified proteins were obtained through denaturation, renaturation and ultrafiltration. After three rounds of immunization with the Eecto protein, the serum of BALB/c mice was obtained and the titer of polyclonal antibodies in serum was determined. The reactivity of polyclonal antibodies was analyzed with Western blotting and immunofluorescence assay in HEK293T cells expressing the ZIKV prME. Spleen cells from mice with higher antibody titers were prepared and fused with SP2/0 myeloma cells. The hybridoma cells secreting antibodies were screened through the limited dilution method, and the ascites containing antibody were harvested for titer measurement and subclass analysis. The Eecto from the envelope proteins of Japanese encephalitis virus (JEV), Yellow fever virus (YFV), Dengue virus (DENV1-4), and Tick borne encephalitis virus (TBEV) were coated and used to analyze the cross-reactivity of ZIKV monoclonal antibodies by ELISA. Further specificity analysis was conducted on antibodies with high titers and strong specificity. Results The plasmid pET28a-ZIKV-Eecto was successfully constructed. The purified Eecto protein was obtained with good immunogenicity. Four monoclonal antibodies were prepared and screened, namely 1D6, 4F11, 4H7, and 4F8. Among them, 1D6, 4H7, and 4F8 are IgG (K) type antibodies, and 4F11 is an IgM (K) antibody. The ascitic fluid titer of 1D6 was higher than 1:108. Antibodies 1D6 and 4H7 are ZIKV-specific and showed no cross-reactivity with other Flaviviruses. Conclusion The mice monoclonal antibodies against ZIKV-Eecto are produced successfully, which will provide experimental materials for the establishment of ZIKV detection methods and the study of its pathogenesis.

Comparative efficacy and safety of ginkgo-based Chinese patent medicines in patients with hypertension: A systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: The efficacy and safety of different oral ginkgo-based Chinese patent medicines (CPMs) regimens for hypertension patients were analyzed based on the network meta-analysis of the frequency framework. METHODS: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database to gather data on randomized controlled trials (RCTs) evaluating the efficacy of 8 ginkgo biloba oral preparations for the treatment of hypertension. The trials included in the analysis were conducted from the inception of the databases up to September 2023. Methodological quality and risk of bias were assessed using the RoB 2.0 evaluation tool, and a reticulated meta-analysis was conducted using STATA MP 14 software. The RCTs included in this study were published studies and therefore did not require ethics committee review or patient consent. RESULTS: We ultimately included 46 RCTs covering 8 CPMs including ginkgo biloba tablet (GBT), GB capsule (GBC), ginkgo biloba drop (GBD), ginkgo biloba ketone ester drop, Fufangyinxing capsule, fufangyinxingtongmai oral liquid, Yinxingmihuan oral liquid, Yindanxinanotong softgel capsule (YDXNT). GBD + CT demonstrated the highest effectiveness in reducing systolic blood pressure (surface under the cumulative ranking [SUCRA] = 78.7%) and improving total effective rate (SUCRA = 86.7%). GBC + CT exhibited the greatest efficacy in reducing diastolic blood pressure (SUCRA = 92.6%). GBT + CT was identified as the most effective in lowering total cholesterol (TC) (SUCRA = 100%). Additionally, YDXNT + CT demonstrated notable improvements in triglyceride levels (SUCRA = 92.2%), Nitric oxide (NO) (SUCRA = 93.9%), and ET-1 (SUCRA = 67.5%). In terms of safety, 14 studies reported the occurrence of adverse reactions with a high degree of clinical heterogeneity, which was only qualitatively analyzed in this study. CONCLUSION SUBSECTIONS: We found that a combination of 8 ginkgo-based CPMs + CT was effective in hypertension compared with CT. The evidence showed that GBD + CT were the best in improving systolic blood pressure and total effective rate, GBC + CT improved diastolic blood pressure, GBT + CT were the most effective in improving TC, and YDXNT + CT was the most effective in improving TG, NO, and ET-1. Adverse effects were only analyzed qualitatively, and the number of adverse effects of CPMs treatment was relatively low compared to CT. In addition, the quality of the literature included in the study was low, and further validation through RCTs with larger sample sizes, higher quality, and more rigorously designed is needed.

Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

SLC7A11 as a therapeutic target to attenuate phthalates-driven testosterone level decline in mice.

INTRODUCTION: Phthalates exposure is a major public health concern due to the accumulation in the environment and associated with levels of testosterone reduction, leading to adverse pregnancy outcomes. However, the relationship between phthalate-induced testosterone level decline and ferroptosis remains poorly defined. OBJECTIVES: Herein, we aimed to explore the mechanisms of phthalates-induced testosterone synthesis disorder and its relationship to ferroptosis. METHODS: We conducted validated experiments in vivo male mice model and in vitro mouse Leydig TM3 cell line, followed by RNA sequencing and metabolomic analysis. We evaluated the levels of testosterone synthesis-associated enzymes and ferroptosis-related indicators by using qRT-PCR and Western blotting. Then, we analyzed the lipid peroxidation, ROS, Fe2+ levels and glutathione system to confirm the occurrence of ferroptosis. RESULTS: In the present study, we used di (2-ethylhexyl) phthalate (DEHP) to identify ferroptosis as the critical contributor to phthalate-induced testosterone level decline. It was demonstrated that DEHP caused glutathione metabolism and steroid synthesis disorders in Leydig cells. As the primary metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP) triggered testosterone synthesis disorder accompanied by a decrease in the expression of solute carri1er family 7 member 11 (SLC7A11) protein. Furthermore, MEHP synergistically induced ferroptosis with Erastin through the increase of intracellular and mitochondrial ROS, and lipid peroxidation production. Mechanistically, overexpression of SLC7A11 counteracts the synergistic effect of co-exposure to MEHP-Erastin. CONCLUSION: Our research results suggest that MEHP does not induce ferroptosis but synergizes Erastin-induced ferroptosis. These findings provide evidence for the role of ferroptosis in phthalates-induced testosterone synthesis disorder and point to SLC7A11 as a potential target for male reproductive diseases. This study established a correlation between ferroptosis and phthalates cytotoxicity, providing a novel view point for mitigating the issue of male reproductive disease and "The Global Plastic Toxicity Debt".

PPARγ regulates osteoarthritis chondrocytes apoptosis through caspase-3 dependent mitochondrial pathway.

Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a complex pathogenesis. One of the key factors contributing to its development is the apoptosis of chondrocytes triggered by oxidative stress. Involvement of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported in the regulation of oxidative stress. However, there remains unclear mechanisms that through which PPARγ influences the pathogenesis of OA. The present study aims to delve into the role of PPARγ in chondrocytes apoptosis induced by oxidative stress in the context of OA. Primary human chondrocytes, both relatively normal and OA, were isolated and cultured for the following study. Various assessments were performed, including measurements of cell proliferation, viability and cytotoxicity. Additionally, we examined cell apoptosis, levels of reactive oxygen species (ROS), nitric oxide (NO), mitochondrial membrane potential (MMP) and cytochrome C release. We also evaluated the expression of related genes and proteins, such as collagen type II (Col2a1), aggrecan, inducible nitric oxide synthase (iNOS), caspase-9, caspase-3 and PPARγ. Compared with relatively normal cartilage, the expression of PPARγ in OA cartilage was down-regulated. The proliferation of OA chondrocytes decreased, accompanied by an increase in the apoptosis rate. Down-regulation of PPARγ expression in OA chondrocytes coincided with an up-regulation of iNOS expression, leading to increased secretion of NO, endogenous ROS production, and decrease of MMP levels. Furthermore, we observed the release of cytochrome C, elevated caspase-9 and caspase-3 activities, and reduction of the components of extracellular matrix (ECM) Col2a1 and aggrecan. Accordingly, utilization of GW1929 (PPARγ Agonists) or Z-DEVD-FMK (caspase-3 inhibitor) can protect chondrocytes from mitochondrial-related apoptosis and alleviate the progression of OA. During the progression of OA, excessive oxidative stress in chondrocytes leads to apoptosis and ECM degradation. Activation of PPARγ can postpone OA by down-regulating caspase-3-dependent mitochondrial apoptosis pathway.

An antifouling epoxy coated metal surface containing silica-immobilized carbonic anhydrase supraparticles for CO2 capture through microalgae.

Carbonic anhydrase (CA) has a promising application as a green and efficient biocatalyst for CO2 capture, and many successful cases of immobilizing CA have been reported. However, CA antifouling coatings on metal for CO2 sequestration have rarely been reported. Herein, dimeric CA from Sulfurihydrogenibium azorense (SazCA) with a ferritin tag, which was prepared by low-speed centrifugation with high yield, was adopted as a free enzyme and encapsulated in the sol-gel silica. The silica-immobilized CAs were dispersed into the commercialized metal-antifouling epoxy resin paint to obtain CA coated nickel foams, which had excellent stability, with 90 % and 67 % residual activity after 28 days of incubation at 30 °C and 60 °C, respectively. The CA coated nickel foams remained 60 % original activity after 6 cycles of use within 28 days. Then, a CA-microalgae carbon capture device was constructed using the CA coated nickel foams and Chlorella. The growth rate of Chlorella was significantly increased and the biomass of Chlorella increased by 29 % compared with control after 7 days of incubation. Due to the simple and cost-effective preparation process, sustainable and efficient CO2 absorption, this easy-to-scale up CA coated nickel foam has great potential in CA assisted microalgae-based CO2 capture and carbon neutrality.

Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.

Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7 min (95% limits of agreement (LoA): -37.8-107.2 min) for total sleep duration, 2.6 min for REM duration (95% LoA: -68.4-73.4 min) and 32.1 min (95% LoA: -54.4-118.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6 h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.

DDX39B protects against sorafenib-induced ferroptosis by facilitating the splicing and cytoplasmic export of GPX4 pre-mRNA in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer and remains one of the most common solid malignancies globally. Ferroptosis was recently defined as an iron-catalyzed form of regulated necrosis. Because cancer cells exhibit higher iron requirements than noncancer cells, treatment with ferroptosis-inducing compounds may be a feasible strategy for cancer therapy. However, cancer cells develop acquired resistance to evade ferroptosis, and the mechanisms responsible for ferroptosis resistance are not fully clarified. In the current study, we reported that DDX39B was downregulated during sorafenib-induced ferroptosis in a dose- and time-dependent manner. Exogenous introduction of DDX39B ensured the survival of HCC cells upon exposure to sorafenib, while the opposite phenomenon was observed in DDX39B-silenced HCC cells. Mechanistically, we demonstrated that DDX39B increased GPX4 levels by promoting the splicing and cytoplasmic translocation of GPX4 pre-mRNA, which was sufficient to detoxify sorafenib-triggered excess lipid ROS production, lipid peroxidation accumulation, ferrous iron levels, and mitochondrial damage. Inhibition of DDX39B ATPase activity by CCT018159 repressed the splicing and cytoplasmic export of GPX4 pre-mRNA and synergistically assisted sorafenib-induced ferroptotic cell death in HCC cells. Taken together, our data uncover a novel role for DDX39B in ferroptosis resistance by modulating the maturation of GPX4 mRNA via a posttranscriptional approach and suggest that DDX39B inhibition may be a promising therapeutic strategy to enhance the sensitivity and vulnerability of HCC cells to sorafenib.