Search

Abstract Background Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses. Methods This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers. Results Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1β, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities. Conclusions High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.

Aim: Ovarian cancer (OC) is the most lethal gynecological malignancy, which seriously affects the prognosis and life quality of female patients. Therefore, new therapeutic targets and treatments are urgently needed. Methods: Expression levels of miR-93-5p and SLC7A11 and ferroptosis status in paracancerous and tumor tissues were examined and compared. The effect of the miR-93-5p-SLC7A11 regulatory loop on the malignant phenotype as well as the ferroptosis phenotype of SKOV3 cells was assessed. Furthermore, the interaction between miR-93-5p and SLC7A11 was confirmed via rescue experiment. Results: In this study, we found that miR-93-5p was lowly expressed in cancer tissues, and suggested that overexpression of miR-93-5p could target SLC7A11 to reduce its expression and promote ferroptosis, thereby inhibiting the malignant biological behaviors such as proliferation, invasion and migration, while knockdown of miR-93-5p restrained ferroptosis and promoting tumor growth. Besides, erastin, as a specific inhibitor of SLC7A11, could target down the expression of SLC7A11, induce the occurrence of ferroptosis, and reverse the effect of knockdown of miR-93-5p. Conclusions: Taken together, our findings disclosed that miR-93-5p increased the level of ferroptosis and inhibited the progression of OC by targeting and inhibiting the expression level of SLC7A11, which was a potential treatment in OC.

Abstract In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.

The emulsification stability of microalgae protein (MP) is limited to strongly alkaline conditions, restricting its applications in food processing. This study aims to investigate the capability of carboxymethyl chitosan (CMCS) to improve MP's emulsification stability over a wider pH range. Results indicated soluble MP-CMCS complexes formed at pH 2, 4, and 7, while aggregation of the complexes occurred at pH 8. The complexes stabilized emulsions exhibited smaller droplet sizes and higher absolute zeta potential at pH 2, 4, and 7 compared to pH 8. After 2 weeks of storage, emulsions remained stable at pH 2, 4, and 7, with significant delamination at pH 8. Laser confocal microscopy confirmed uniform droplet distribution at pH 2 and 7, with slight fusion at pH 4. The complexes stabilized emulsions exhibited higher viscosity and shear stress than MP stabilized emulsions at pH 2, 4, and 7. The stronger viscoelastic properties and higher storage moduli (G') values of MP-CMCS complexes under acidic and neutral conditions indicated stronger intermolecular interactions compared to alkaline conditions. The increase in G' and loss moduli (G'') values for emulsions at pH 8 under stress highlighted the significant impact on network structure strength and viscosity in these emulsions. This study elucidated the binding interactions between MP and CMCS under various pH conditions, and demonstrated a feasible approach to improving MP's emulsification stability over a wider pH range.

Atrial fibrosis is the hallmark of structural remodeling in the pathogenesis of atrial fibrillation (AF). Meanwhile, AF causes a hypercoagulable state, and then provokes pro-fibrotic response. To discover a potential effective AF treatment targeting both coagulation and atrial fibrosis, this study investigated the structure–activity relationship of propylene glycol alginate sodium sulfate (PSS) derivatives with heparin-like activity on TGF-β1-induced atrial fibrosis. We found that PSS derivatives had significantly inhibitory effects on proliferation, migration, phenotypic transformation, and secretion/deposition of extracellular matrix of atrial fibroblasts. Among them, PGGS showed the optimal anti-atrial fibrotic activity by suppressing TGF-β1-induced activation of Smad2/3 signaling pathway. Furthermore, the study in vivo indicated that PGGS treatment displayed a reduced atrial fibrosis and AF inducibility, and attenuated the hypercoagulable state by decreasing D-dimer level and thrombin (FIIa) activity in MHC-TGF-β1 cys33ser transgenic mice, which had increased fibrosis in atrium but not in the ventricles. Our results demonstrated that PSS derivatives, especially PGGS, were potential anti-atrial fibrosis and anti-coagulant agents for AF prevention. Our study is beneficial in extending the current understandings of the function of PSS on atrial fibrosis and vulnerability to AF.

BackgroundObstruction is a common complication of advanced colorectal cancer. This study was aimed at investigating the safety, efficacy, and feasibility of transcatheter arterial perfusion chemotherapy combined with lipiodol chemoembolization for treating advanced colorectal cancer complicated by obstruction.Patients and methodsThis retrospective analysis was conducted using clinical data of patients with advanced colorectal cancer who received arterial infusion chemotherapy combined with lipiodol chemoembolization treatment at our center. Treatment efficacy was evaluated in terms of obstruction-free survival and overall survival, and treatment complications were monitored.ResultsFifty-four patients with colorectal cancer complicated by obstruction were included. All patients successfully underwent transcatheter arterial infusion combined with lipiodol chemoembolization treatment. The average lipiodol dose administered was 2.62 ± 1.45 ml (0.5–5.5 ml). No serious complications such as perforation or tumor dissemination occurred. The clinical success rate was 83.3% (45/54). One month after treatment, the objective response rate (ORR) and disease control rate (DCR) were 66.67% and 88.9%, respectively. The median obstruction-free survival was 5.0 months. No serious adverse events occurred. As of the last follow-up, 6 patients survived, 44 died, and 4 were lost to follow-up.ConclusionOur findings revealed that transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization is safe and effective for treating advanced colorectal cancer complicated by obstruction. It may serve as a new treatment strategy for patients with advanced colorectal cancer complicated by obstruction.

Abstract Background Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). Methods A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. Results We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816–0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716–0.805). Conclusions These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.

Abstract Background Patients with complex phenotypes and a chromosomal translocation are particularly challenging, since several potentially pathogenic mechanisms need to be investigated. Case presentation Here, we combined exome and genome sequencing techniques to identify the precise breakpoints of heterozygous microduplications in the 6q25.3-q27 region and microdeletions in the 2q37.1-q37.3 region in a proband. The 5-year-old girl exhibited a severe form of congenital cranial dysinnervation disorder (CCDD) in addition to skeletal dysmorphism anomalies and severe intellectual disability. This is the second case affecting chromosomes 2q and 6q. The individual’s karyotype showed an unbalanced translocation 46,XX,del(2)t(2;6)(q37.1;q25.3), which was inherited from her unaffected father [46,XY,t(2;6)(q37.1;q25.3)]. We also obtained the precise breakpoints of a de novo heterozygous copy number deletion [del(2)(q37.1q37.3)chr2:g.232963568_24305260del] and a copy number duplication [dup(6)(q25.3q27)chr6:g.158730978_170930050dup]. The parental origin of the observed balanced translocation was not clear because the parents declined genetic testing. Conclusion Patients with a 2q37 deletion and 6q25.3 duplication may exhibit severe significant neurological and skeletal dysmorphisms, and the utilization of exome and genome sequencing techniques has the potential to unveil the entire translocation of the CNV and the precise breakpoint.

Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of proinflammatory factors in macrophages stimulated by lipopolysaccharide (LPS). Multiplex proteomic profiling identified the immunoproteasome, which is a specific isoform of the 20s constitutive proteasome, as a substrate that is degraded by selective autophagy. SQSTM1/p62 was found to be a selective autophagy-related receptor that mediated this degradation. Autophagy deficiency or p62 knockdown blocked the effects of LY2874455, leading to the accumulation of immunoproteasomes and increases in inflammatory reactions. Expression of proinflammatory factors in autophagy-deficient macrophages could be reversed by immunoproteasome inhibitors, confirming the pivotal role of immunoproteasome turnover in the autophagy-mediated suppression on the expression of proinflammatory factors. In mice, LY2874455 protected against LPS-induced acute lung injury and dextran sulfate sodium (DSS)-induced colitis and caused low levels of proinflammatory cytokines and immunoproteasomes. These findings suggested that selective autophagy of the immunoproteasome was a key regulator of signaling via the innate immune system.

This study aimed to investigate whether and how nighttime warming (NW) influences the copper (Cu) bioaccumulation of wheat (Triticum aestivum L.) under Cu pollution. We examined plant growth, Cu concentration, and antioxidant enzymes of wheat after 6 months of Cu exposure (0, 100, 400, and 800 mg/kg) under NW. The results indicated that, NW of 1.54°C significantly promoted Cu translocation from root to shoot through an increasing root system under increased Cu treatments (p < 0.05). The Cu contents of grains were significantly increased by NW under 800 mg/kg Cu treatment (p < 0.05). NW decreased superoxide dismutase (SOD) activity under increased Cu treatments (p < 0.05). There were significantly negative correlations between biomass and Cu concentrations of the same part under NW (p < 0.05). The root biomass significantly increased by 51% in NW compared with nonnighttime warming (CK) (p < 0.05). These results provided evidence that wheat might respond to NW by altering their roots so that they were larger, thinner, and longer, suggesting that soil Cu translocation from root to shoot would be accelerated resulting from the expanded roots under elevated temperatures, and thus forewarned the food safety risks of climate change in agricultural ecosystem.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and is one of the primary causes of blindness in the working-age population in Europe and the United States. At present, no cure is available for DR, but early detection and timely intervention can prevent the rapid progression of the disease. Several treatments for DR are known, primarily ophthalmic treatment based on glycemia, blood pressure, and lipid control, which includes laser photocoagulation, glucocorticoids, vitrectomy, and antivascular endothelial growth factor (anti-VEGF) medications. Despite the clinical efficacy of the aforementioned therapies, none of them can entirely shorten the clinical course of DR or reverse retinopathy. MicroRNAs (miRNAs) are vital regulators of gene expression and participate in cell growth, differentiation, development, and apoptosis. MicroRNAs have been shown to play a significant role in DR, particularly in the molecular mechanisms of inflammation, oxidative stress, and neurodegeneration. The aim of this review is to systematically summarize the signaling pathways and molecular mechanisms of miRNAs involved in the occurrence and development of DR, mainly from the pathogenesis of oxidative stress, inflammation, and neovascularization. Meanwhile, this article also discusses the research progress and application of miRNA-specific therapies for DR.

IntroductionTrichoderma spp. is a recognized bio-control agent that promotes plant growth and enhances resistance against soil-borne diseases, especially Fusarium wilt. It is frequently suggested that there is a relationship between resistance to melon wilt and changes in soil microbiome structures in the rhizosphere with plant metabolites. However, the exact mechanism remains unclear.MethodThis study aims to investigate the effects of Trichoderma application on the metabolic pathway of oriental melon roots in response to Fusarium oxysporum f. sp. melonis in a pot experiment. The experiment consisted of three treatments, namely water-treated (CK), FOM-inoculated (KW), and Trichoderma-applied (MM) treatments, that lasted for 25 days. Ultra-performance liquid chromatography-electron spray ionization-mass spectrometry (UPLC-ESI-MS) was used to analyze the compounds in melon roots.ResultsThe results show that Trichoderma harzianum application resulted in a reduction in the severity of oriental melon Fusarium wilt. A total of 416 distinct metabolites, categorized into four groups, were detected among the 886 metabolites analyzed. Additionally, seven differential metabolites were identified as key compounds being accumulated after inoculation with Fusarium oxysporum f. sp. melonis (FOM) and Trichoderma. The mechanism by which Trichoderma enhanced melon's resistance to Fusarium wilt was primarily associated with glycolysis/gluconeogenesis, phenylpropanoid biosynthesis, flavone and flavonol biosynthesis, and the biosynthesis of cofactors pathway. In comparison with the treatments of CK and MM, the KW treatment increased the metabolites of flavone and flavonol biosynthesis, suggesting that oriental melon defended against pathogen infection by increasing flavonol biosynthesis in the KW treatment, whereas the application of Trichoderma harzianum decreased pathogen infection while also increasing the biosynthesis of glycolysis/gluconeogenesis and biosynthesis of cofactors pathway, which were related to growth. This study also aims to enhance our understanding of how melon responds to FOM infection and the mechanisms by which Trichoderma harzianum treatment improves melon resistance at the metabolic level.

Abstract Background Esophagojejunal anastomotic leakage is a serious complication after total gastrectomy. This study evaluated the safety and efficacy of transnasal placement of drainage catheter, jejunal decompression tube, and jejunal nutrition tube under fluoroscopy for treatment of esophagojejunal anastomotic fistula after gastrectomy in gastric cancer patients. Methods This is retrospective review of patients with esophagojejunal anastomotic fistula treated with transnasal placement of abscess drainage catheter, decompression tube, and jejunal nutrition tube under fluoroscopy. Fistula healing time, patient survival, and Eastern Cooperative Oncology Group (ECOG) performance status before and after treatment were evaluated. Results Sixty-four patients were included in the study. Insertion of the transnasal abscess drainage catheter, decompression tube, and jejunal nutrition tube was successful on the first attempt in all patients, while 35 patients received transnasal abscess drainage, 13 received percutaneous abscess drainage, and 16 received transnasal drainage plus percutaneous abscess drainage. Immediately after placement of the tube, the mean volume of drainage was 180 mL (range, 10–850 mL); the amount steadily decreased from then on. The clinical success rate was 84.3% (54/64). Median time to fistula healing was 58 days (range, 7–357 days). Conclusions Transnasal insertion of transnasal abscess drainage catheter, jejunal decompression tube, and jejunal nutrition tube under fluoroscopy appears to be a simple, minimally invasive, effective, and safe method for treating esophagojejunal anastomotic fistula after gastrectomy.

Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH of N-acetyl-galactosamine has been found. Here, using functionalized monosaccharide building blocks, we prepared novel FCS tetrasaccharides with fucosyl branches both at the 6-OH of GalNAc and 3-OH of GlcA. In the synthesis, the protective group strategy of selective O-sulfation, as well as stereoselective glycosylation, was established, which enabled the efficient synthesis of the specific tetrasaccharide compounds. This research enriches knowledge on the structural types of FCS oligosaccharides and facilitates the exploration of the structure–activity relationship in the future.

Abstract Background Tibetans are genetically adapted to high-altitude environments. Though many studies have been conducted, the genetic basis of the adaptation remains elusive due to the poor reproducibility for detecting selective signatures in the Tibetan genomes. Results Here, we present whole-genome sequencing (WGS) data of 1001 indigenous Tibetans, covering the major populated areas of the Qinghai–Tibetan Plateau in China. We identify 35 million variants, and more than one-third of them are novel variants. Utilizing the large-scale WGS data, we construct a comprehensive map of allele frequency and linkage disequilibrium and provide a population-specific genome reference panel, referred to as 1KTGP. Moreover, with the use of a combined approach, we redefine the signatures of Darwinian-positive selection in the Tibetan genomes, and we characterize a high-confidence list of 4320 variants and 192 genes that have undergone selection in Tibetans. In particular, we discover four new genes, TMEM132C, ATP13A3, SANBR, and KHDRBS2, with strong signals of selection, and they may account for the adaptation of cardio-pulmonary functions in Tibetans. Functional annotation and enrichment analysis indicate that the 192 genes with selective signatures are likely involved in multiple organs and physiological systems, suggesting polygenic and pleiotropic effects. Conclusions Overall, the large-scale Tibetan WGS data and the identified adaptive variants/genes can serve as a valuable resource for future genetic and medical studies of high-altitude populations.

ABSTRACTUrinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) can lead to severe kidney injury. However, the molecular mechanisms underlying the pathological process of kidney injury are still incompletely understood. In the present study, we demonstrate that microRNA-146b (miR-146b) deficiency aggravates kidney injury during UTIs caused by UPEC. In a mouse kidney infection model utilizing urosepsis isolate CFT073, we found that miR-146b expression significantly increased in the early stages of UPEC infection. Also, miR-146b-deficient mice displayed exacerbated inflammation in the kidney injury with severe M1 macrophage infiltration. Additionally, the results showed that miR-146b targeted interferon regulatory factor 5-regulated M1 macrophage polarization during UTIs. The results suggested that miR-146b contributed significantly to the control of kidney damage during UTIs, highlighting that miR-146b might be used as a novel therapeutic target for treating kidney injury during UTIs.IMPORTANCEKidney injury during acute urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) is an important public health problem. However, how kidney injury develops during UPEC infection is still unclear. Although antibiotic therapy is currently an effective treatment for UTI, it cannot avoid kidney injury. MicroRNAs have gained extensive attention as essential molecules capable of regulating the autoimmune response. Among these, microRNA-146b (miR-146b) is involved in regulating inflammatory responses. In the present study, we demonstrated that miR-146b played an essential role in the development of kidney injury during UTIs caused by UPEC. The results showed that miR-146b may suppress M1 macrophage polarization and alleviate acute kidney injury. Furthermore, the miR-146b activator, agomir, in order to upregulate miR-146b, was effective in treating kidney damage by inhibiting the activation of M1 macrophages. In conclusion, our findings elucidated the mechanisms by which miR-146b alleviated kidney injury induced by UTIs, shed new light on the relationship between microRNA and bacterial infection, and provided a novel therapeutic target for treating this common bacterial infection.

Macrophages are highly heterogeneous and plastic, and have two main polarized phenotypes that are determined by their microenvironment, namely pro- and anti-inflammatory macrophages. Activation of pro-inflammatory macrophages is closely associated with metabolic reprogramming, especially that of aerobic glycolysis. Mitochondrial pyruvate dehydrogenase kinase (PDK) negatively regulates pyruvate dehydrogenase complex activity through reversible phosphorylation and further links glycolysis to the tricarboxylic acid cycle and ATP production. PDK is commonly associated with the metabolism and polarization of macrophages in metabolic and inflammatory diseases. This review examines the relationship between PDK and macrophage metabolism and discusses the mechanisms by which PDK regulates macrophage polarization, migration, and inflammatory cytokine secretion in metabolic and inflammatory diseases. Elucidating the relationships between the metabolism and polarization of macrophages under physiological and pathological conditions, as well as the regulatory pathways involved, may provide valuable insights into the etiology and treatment of macrophage-mediated inflammatory diseases.

Background It remains controversial whether changes of lipids over menopause transition (MT) are more age‐related or more menopause‐related. We aimed to classify women into different trajectory groups based on pattern and level of total cholesterol, low‐density lipoprotein cholesterol, apolipoprotein B (ApoB), high‐density lipoprotein cholesterol (HDL‐C), triglyceride, and apolipoprotein A‐I over the MT, as well as examine the effect of MT‐related factors on lipid trajectory groups and levels. Methods and Results The cohort included 2582 subjects from the Study of Women's Health Across the Nation. Different trajectory patterns of lipids during the MT were determined using the latent class growth mixture model. The predictors of distinct blood lipids trajectory groups were determined by multiple linear regression models and multinomial logistic regression models. Women were categorized into either inverse U‐shape or progressing trajectory group in each blood lipids measurement. The inverse U‐shape total cholesterol, low‐density lipoprotein cholesterol, apolipoprotein B, high‐density lipoprotein cholesterol, log(TG), and apolipoprotein A‐I trajectories showed an increasing trend before menopause but a decreasing trend after menopause. The U‐shape total cholesterol, low‐density lipoprotein cholesterol, and apolipoprotein B trajectories started to rise 5 years before menopause. Age at menopause, follicle‐stimulating hormone, vasomotor symptoms, and estradiol predicted the shape and level of the women's lipids over the MT. Conclusions Distinct lipid trajectories were identified during the MT, and the existence of at least 1 trajectory in each lipid parameters suggested a contribution of menopause. Our study highlights the need for earlier and continuous surveillance of lipids during the MT.

Mung bean is a dual-use crop widely cultivated in Southeast Asia as a food and medicine resource. The development of new functional mung bean varieties demands identifying new genes regulating anthocyanidin synthesis and investigating their molecular mechanism. In this study, we used high-throughput sequencing technology to generate transcriptome sequence of leaves, petioles, and hypocotyls for investigating the anthocyanins accumulation in common mung bean variety as well as anthocyanidin rich mung bean variety, and to elucidate their molecular mechanisms. 29 kinds of anthocyanin compounds were identified. Most of the anthocyanin components contents were significantly higher in ZL23 compare with AL12. Transcriptome analysis suggested that a total of 93 structural genes encoding the anthocyanin biosynthetic pathway and 273 regulatory genes encoding the ternary complex of MYB-bHLH-WD40 were identified, of which 26 and 78 were differentially expressed in the two varieties. Weighted gene co-expression network analysis revealed that VrMYB3 and VrMYB90 might have enhanced mung bean anthocyanin content by inducing the expression of structural genes such as PAL, 4CL, F3’5’H, LDOX, and F3’H, which was consistent with qRT-PCR results. These findings are envisaged to provide a reference for studying the molecular mechanism of anthocyanin accumulation in mung beans.

Abstract. Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.

Abstract Background Current prognostic prediction models of colorectal cancer (CRC) include only the preoperative measurement of tumor markers, with their available repeated postoperative measurements underutilized. CRC prognostic prediction models were constructed in this study to clarify whether and to what extent the inclusion of perioperative longitudinal measurements of CEA, CA19-9, and CA125 can improve the model performance, and perform a dynamic prediction. Methods The training and validating cohort included 1453 and 444 CRC patients who underwent curative resection, with preoperative measurement and two or more measurements within 12 months after surgery, respectively. Prediction models to predict CRC overall survival were constructed with demographic and clinicopathological variables, by incorporating preoperative CEA, CA19-9, and CA125, as well as their perioperative longitudinal measurements. Results In internal validation, the model with preoperative CEA, CA19-9, and CA125 outperformed the model including CEA only, with the better area under the receiver operating characteristic curves (AUCs: 0.774 vs 0.716), brier scores (BSs: 0.057 vs 0.058), and net reclassification improvement (NRI = 33.5%, 95% CI: 12.3 ~ 54.8%) at 36 months after surgery. Furthermore, the prediction models, by incorporating longitudinal measurements of CEA, CA19-9, and CA125 within 12 months after surgery, had improved prediction accuracy, with higher AUC (0.849) and lower BS (0.049). Compared with preoperative models, the model incorporating longitudinal measurements of the three markers had significant NRI (40.8%, 95% CI: 19.6 to 62.1%) at 36 months after surgery. External validation showed similar results to internal validation. The proposed longitudinal prediction model can provide a personalized dynamic prediction for a new patient, with estimated survival probability updated when a new measurement is collected during 12 months after surgery. Conclusions Prediction models including longitudinal measurements of CEA, CA19-9, and CA125 have improved accuracy in predicting the prognosis of CRC patients. We recommend repeated measurements of CEA, CA19-9, and CA125 in the surveillance of CRC prognosis.

Combined chemodynamic/photothermal therapy has great potential in tumor treatment. However, the presence of excessive glutathione (GSH) in the tumor microenvironment (TME) can attenuate its therapeutic effect, and other components in the TME have not been fully utilized as well. In this article, we designed a noble metal nanozyme called PdCu@BSA, which can be used for the combined chemodynamic therapy (CDT) and photothermal therapy (PTT) of tumor. In detail, PdCu@BSA has three different types of enzyme-like activities. Its catalase (CAT)-like activity can degrade extra H _2 O _2 in the TME to create O _2 and relieve the hypoxic situation. The glutathione oxidase (GSHox)-like activity can consume high level of GSH in the TME to reduce the consumption of reactive oxygen species (ROS). Peroxidase (POD)-like activity catalyzes H _2 O _2 to form strong oxidized ·OH. The above enzyme-like activities enhance the effectiveness of CDT. Besides, PdCu@BSA has good photothermal effect and can be used for PTT when exposed to 1064 nm laser. Therefore, based on multiple enzyme-like activities and photothermal effects, PdCu@BSA can be employed for synergistic tumor therapy, resulting in good therapeutic outcome.

PurposeThis study aimed to investigate the safety and efficacy of transarterial infusion chemotherapy for the treatment of esophageal cancer with airway stenosis.MethodsData of patients with advanced esophageal cancer complicated with airway stenosis treated with transarterial infusion chemotherapy were retrospectively analyzed. Dyspnea, clinical efficacy and adverse reactions were evaluated.ResultsOf these patients, 27 had grade II preoperative dyspnea, and 31 had grade III preoperative dyspnea, 26 had grade I postoperative dyspnea, 25 had grade II postoperative dyspnea, and 7 had grade III postoperative dyspnea. Among 3 patients with left main bronchial stenosis and atelectasis, 2 had complete remission after transarterial infusion chemotherapy, and 1 demonstrated partial remission. After treatment, complete response, partial response, and stable disease were observed in 7, 34, and 17 cases, respectively. Total objective effective rate and disease control rate were 70.6% (41/58) and 100.0%, respectively. During follow up, 24 patients died of organ failure, and 17 patients died of tumor-related respiratory failure. Seven patients died of gastrointestinal bleeding, 1 patient died of myocardial infarction, and 9 patients survived.ConclusionsTransarterial infusion chemotherapy is safe and effective for the treatment of advanced esophageal cancer with airway stenosis.

Abstract Objective To investigate the manifestation of dry eye and its relationship with CXCR3 and CCR5 expression in patients with ocular acid burns. Methods This is a case–control study. A total of 27 eyes of 22 cases ocular with acid burns of I-V degrees from Jan.2020 to Feb.2021 in Jinshan Hospital of Fudan University were selected as observation group, and 8 eyes of 8 cases of normal people were selected as control group. The follow-up period was 3 months. The visual acuity, intraocular pressure (IOP), corneal fluorescein staining scores (CFS), breakup time of tear film (BUT), Schirmer I test, corneal thickness and tear meniscus height (TMH) were observed at 1 day, 1 and 3 months after injury. The protein expressions of CXCR3 and CCR5 were examined by ELISA and compared among groups at each time point. Results BUT and Schirmer I tests value in the observation group were lower than those in the control group 3 months after injury (BUT: Group I ~ IV p = 0.0266, p = 0.0222, p = 0.0003, p = 0.0059, respectively; Schirmer I test: Group I ~ IV p = 0.0027, p = 0.0033, p = 0.0016, p = 0.0032, respectively). CFS scores were higher than those in the control group at 1 day after injury (all p

Abstract Objective Whether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified. Methods Consecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale. Results A total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724). Conclusions Preoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Abstract Acute radiation proctitis (ARP) is one of the most common complications of pelvic radiotherapy attributed to radiation exposure. The mechanisms of ARP are related to inflammation, angiogenesis, and so on. In this study we evaluated the effect of dexamethasone (DXM) combined with gentamicin (GM) enema on ARP mice, and explored its possible mechanisms by transcriptome sequencing, western blot and immunohistochemistry. C57BL/6 mice were randomly divided into 3 groups: healthy control group, ARP model group, and DXM + GM enema treatment group. ARP mice were established by using a single 6 MV X-ray dose of 27 Gy pelvic local irradiation. Transcriptome sequencing results showed that 979 genes were co-upregulated and 445 genes were co-downregulated in ARP mice compared to healthy mice. According to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, we firstly found that PI3K/AKT/NF-κB/VEGF pathways were mostly correlated with the inflammation-induced angiogenesis in ARP mice. PI3K/AKT pathway leads to the activation of NF-κB, which promotes the transcription of VEGF and Bcl-2. Interestingly, symptoms and pathological changes of ARP mice were ameliorated by DXM + GM enema treatment. DXM + GM enema inhibited inflammation by downregulating NF-κB and upregulating AQP3, as well as inhibited angiogenesis by downregulating VEGF and AQP1 in ARP mice. Moreover, DXM + GM enema induced apoptosis by increasing Bax and suppressing Bcl-2. The novel mechanisms may be related to the downregulation of PI3K/AKT/NF-κB/VEGF pathways.

Curcumin (CU) is a bioactive compound extracted from turmeric and has various advantages. However, the benefit of CU is limited by its low water solubility (11 ng/mL). This research aimed to fabricate a water-soluble CU nano-formulation with chitooligosaccharides (COS) and pluronic F-68 (PF) utilizing the polymeric micelle method. The optimized curcumin-loaded chitooligosaccharides/pluronic F-68 micelles (COSPFCU) exhibited high encapsulation efficiency and loading capacity (75.57 ± 2.35% and 10.32 ± 0.59%, respectively). The hydrodynamic diameter of lyophilized COSPFCU was 73.89 ± 11.69 nm with a polydispersity index below 0.3. The COSPFCU could be completely redispersed in water and showed high DPPH scavenging ability. Meanwhile, COSPFCU could significantly reduce the cytotoxicity of the RAW 264.7 cells compared to native CU. Furthermore, COSPFCU improved the inhibition of NO release activity at 72.83 ± 2.37% but 33.20 ± 3.41% for the CU, with a low cytotoxicity concentration in the RAW 264.7 cells.

Abstract The purpose of this clinical study was to investigate the efficacy and safety of airway stent implantation and transarterial infusion chemotherapy in the sequential treatment of severe airway stenosis caused by esophageal cancer. Data of patients with advanced esophageal cancer complicated by severe airway stenosis treated with airway stent implantation and transarterial infusion chemotherapy were retrospectively analyzed. Furthermore, dyspnea, clinical efficacy, adverse reactions, and survival of patients were evaluated. 71 patients were included in this study. There were 28 patients with grade III dyspnea and 43 patients with grade IV dyspnea before airway stent implantation, and 34 patients with grade I dyspnea, 35 patients with grade II dyspnea and 2 patients with grade III dyspnea after airway stent implantation. After airway stent implantation and 1–3 courses of transarterial infusion chemotherapy, 11, 41 and 19 patients had complete response, partial response and stable response respectively. Total disease control rate (DCR) and objective response rate (ORR) were 100.0% and 73.2%, respectively. During the follow-up, 32 patients died of organ failure, 24 patients died of tumor-related respiratory failure, and 10 patients died of gastrointestinal bleeding. The median survival time of all patients was 8 months, and the 1-year survival rate was 40.8%. Airway stent implantation combined with arterial infusion chemotherapy is safe and effective for sequential treatment of esophageal cancer with severe airway stenosis.

Cancer has always been a terrible disease threatening human life. Although many researches have been carried out on cancer, there is still no way to cure it. Emerging therapeutic methods, such as photodynamic therapy (PDT), photothermal therapy (PTT), and immunotherapy, have brought the dawn for tumor treatment. As a typical photosensitizer (PS), tetrakis (4‐carboxyphenyl) porphyrin (TCPP) is favored by researchers. TCPP itself has powerful performance, which can be modified and coupled to obtain nanotherapeutic agents with excellent therapeutic effects. What's more, metal–organic frameworks (MOFs) seem tailor‐made for the TCPP. MOFs with stable structure, large surface area, and aperture structure give TCPP more potential for application. With this in mind, the researches of TCPP‐based nanocomposites in tumor therapy in recent years are summarized, and the challenges in the tumor therapy of TCPP‐based nanocomposites and possible research directions to achieve highly efficient therapeutic effects are discussed.

Abstract Amyloid‐β (Aβ) and Tau proteins are the main components of Aβ plaques and neurofibrillary tangles in Alzheimer's disease (AD), and their abnormal aggregation is closely related to the pathogenesis of AD. The production of reactive oxygen species (ROS) and the aggregation of Aβ and Tau form a vicious circle, which leads to the aggravation of AD. However, inhibiting the aggregation of Aβ and Tau or scavenging ROS is not able to effectively reverse the progression of AD. Herein, we prepared a H2O2 responsive multifunctional nanocomposite UCNPs@mSiO2‐MB@AuNPs (abbreviated as USMA) to inhibit the aggregation of Aβ and Tau. In this system, USMA could respond to H2O2 to detach gold nanoparticles (AuNPs) and lead to the release of methylene blue (MB) from mesoporous silica (mSiO2), where AuNPs and MB can inhibit Aβ and Tau aggregation, respectively. Furthermore, USMA could consume H2O2 by reacting with them. Meanwhile, upconversion luminescence of UCNPs can be used to track USMA and monitor MB release, which could provide information on the content of MB in the lesion area. Importantly, the USMA can effectively reduce the cytotoxicity induced by Aβ and Tau aggregation. This work opens up a possibility to improve therapeutic efficacy for the treatment of AD.

Although psoriasis is classified as a T cell-mediated inflammatory disease, the contribution of myeloid cells to the pathogenesis of psoriasis is not fully understood. In the present study, we demonstrated that the expression of the anti-inflammatory cytokine interleukin-35 (IL-35) was significantly increased in patients with psoriasis with a marked increase in the number of myeloid-derived suppressor cells (MDSCs). Similar results were obtained in an imiquimod-induced psoriasis mouse model. IL-35 reduced the total number of MDSCs and their subtypes in the spleens and psoriatic skin lesions, ameliorating psoriasis. IL-35 also reduced the expression of inducible nitric oxide synthase in MDSCs, although it had no significant effect on interleukin-10 expression. Adoptive transfer of MDSCs from imiquimod-challenged mice aggravated the disease and weakened the effect of IL-35 in the recipient mice. In addition, mice transferred with MDSCs isolated from inducible nitric oxide synthase knockout mice had milder disease than those with wild-type MDSCs. Furthermore, wild-type MDSCs reversed the effects of IL-35, while MDSCs isolated from inducible nitric oxide synthase knockout mice did not affect IL-35 treatment. In summary, IL-35 may play a critical role in the regulation of iNOS-expressing MDSCs in the pathogenesis of psoriasis, highlighting IL-35 as a novel therapeutic strategy for patients with chronic psoriasis or other cutaneous inflammatory diseases.

Abstract Objective To compare the outcomes of open reduction and hook plate fixation (ORHPF) and modified TightRope loop plate fixation (MTRLPF) in the treatment of Rockwood type III acromioclavicular joint dislocation. Methods This was a retrospective study. Data on 71 patients with Rockwood type III acromioclavicular joint dislocation who underwent either ORHPF (n = 39) or MTRLPF (n = 32) between January 2016 and October 2019 were extracted and analyzed. Baseline data at injury were compared to evaluate the balance. The disabilities of the arm, shoulder, and hand (DASH) score, Constant-Murley score and visual analog scores (VAS) score at 1 month, 3 months, 6 months and 12 months after operation were compared; further, at 12 months coracoclavicular distance and related complications were evaluated and compared. Results Both groups did not differ for any baseline data. At 1 and 3 months after operation, MTRLPF group exhibited a significantly better performance than the ORHPF group in VAS (1 month: 2.4 ± 1.8 vs 3.0 ± 1.7; 3 months: 1.2 ± 1.4 vs 1.8 ± 1.6), Constant-Murley (1 month: 75.2 ± 11.2 vs 63.8 ± 13.7; 3 months: 81.4 ± 9.8 vs 75.8 ± 10.6), DASH (1 month: 33.6 ± 6.8 vs 40.6 ± 6.1; 3 months: 21.2 ± 7.4 vs 25.6 ± 6.6). At 6 months, only Constant-Murley remained marginally significant (p = 0.048). At 12 months, no statistical difference was observed for any outcome variable (all P > 0.05 for VAS, Constant-Murley and DASH), coracoclavicular distance (12.7 ± 1.6 mm vs 12.2 ± 1.6 mm; P = 0.374), or overall complication rate (P = 0.763). Conclusions For Rockwood type III acromioclavicular joint dislocation, both methods can achieve satisfactory 1-year results, but modified minimally invasive TightRope treatment is more advantageous in early functional recovery at 1 and 3-month follow-ups.

Small changes in soil aggregates-associated organic carbon and soil nitrogen (N) can induce huge fluctuations in greenhouse gas emissions and soil fertility. However, there is a knowledge gap regarding the responses to long-term continuous rotation systems, especially in N-fixing and non-N-fixing crop wheat in terms of the distribution of soil aggregates and the storage of soil carbon (C) and N in aggregates in the semiarid calcareous soil of Central China. This information is critical for advancing knowledge on C and N sequestration of soil aggregates in rainfed crop rotation systems. Our aim was to determine which legume (soybean (Glycine max)– or mung bean (Vigna radiata)–wheat (Triticum aestivum) rotation practice is more conducive to the formation of good soil structure and C and N fixation. A 10-year field experiment, including a soybean (Glycine max)–winter wheat (Triticum aestivum) rotation (SWR) with yield increments of 2020 compared to 2010 achieving 18.28% (soybean) and 26.73% (wheat), respectively, and a mung bean (Vigna radiata)–winter wheat rotation (MWR) achieving 32.66% (mung bean) and 27.38% (wheat), as well as farmland fallow, was conducted in Henan Province, China. The soil organic carbon (SOC), N content in the soil, and the soil aggregates were investigated. Legume–wheat rotation cropping enhanced the proportion of the >2 mm soil fractions and reduced the 2 mm aggregate fractions than the MWR. Two legume–winter wheat rotations enhanced the C and N sequestration that varied with soil depths and size fractions of the aggregate. In contrast, the MWR had greater SOC stocks in all fractions of all sizes in the 0–40 cm soil layers. In addition, the greater storage of N in the macro-, micro-, and silt + clay fractions was observed in the 0–30 cm layers; the MWR enhanced the C/N ratios in most of the size aggregates compared with the SWR. The MWR cropping system is more beneficial to the formation of good soil structure and the increasement of C and N reserves in soil. Thus, these findings show that mung bean, in contrast with soybean in the legume–wheat rotation system of a semiarid temperate zone, may offer soil quality improvement.

Natural gas is of great significance to ensuring China's energy security and achieving “carbon neutrality” by 2060. However, the lack of power to decide LNG import pricing and the high resource cost bring challenges to the stable supply of natural gas in China. In this regard, after analyzing the historical evolution laws of global LNG pricing, this paper systematically summarizes the pricing trends of newly signed contracts in 2020, and comparatively analyzes China's long-term LNG import pricing modes and its problems. And the following research results were obtained. First, the global LNG pricing mechanism is more diversified, regional characteristics and “Asian premium” problems are obvious, and different pricing mechanisms complement each other. Second, the newly signed long-term LNG agreement is linked with oil prices to play a dominant role again, and the oil-linked slope declines continuously and presents a dynamic mixed S-curve. Third, China's long-term LNG agreement is linked with oil prices at a high proportion, so there are no market conditions of gas–gas competition and the price review period is long. Finally, several suggestions were proposed for China's LNG import pricing. Firstly, stick to the principles of “short-term flexibility” and “long-term stability”, and make use of multiple modes comprehensively, e.g. gas–gas competition and Brent price linked, instead of completely decoupling oil prices. Secondly, referring to global newly signed contracts and Asian reviewed contracts, adhere to the principle of market parity, improve the price review terms and shorten the review period. Thirdly, the government shall support the construction of natural gas trading centers and futures markets and form the internationally recognized regional benchmark price as soon as possible. Fourthly, make a plan in advance, establish a risk hedging mechanism and control the overall cost of imported LNG resources.

BackgroundBlood pressure levels are correlated with diabetes among middle-aged or older adults. However, longitudinal trajectories of blood pressure during young adulthood and their impact on diabetes have been insufficiently studied.MethodsThe longitudinal cohort consisted of 4,625 adults who had blood pressure and body mass index (BMI) repeatedly measured five to nine times during 18–60 years of age. Distinct systolic blood pressure (SBP) trajectories were identified by a group-based trajectory model. Logistic regression analyses were used to investigate the association between trajectory patterns or quartiles of area under the curve values of SBP trajectories and incident diabetes, respectively.ResultsFour distinct trajectory groups were identified for SBP: normotensive-stable (n = 761, 16.5%), prehypertension-stable (n = 2,381, 51.5%), stage I hypertension-increasing (n = 1,231, 26.6%), and stage II hypertension-increasing (n = 251, 5.4%). Compared with subjects who remained at SBP

Abstract Notwithstanding immune checkpoint blocking (ICB) therapy has made eminent clinical breakthroughs, overcoming immunologically “cold” tumors remains challenging. Here, a cascade potentiated nanomodulator AuPtAg‐GOx is engineered for boosting immune responsiveness. Upon 1064 nm laser irradiation, AuPtAg‐mediated mild photothermal therapy (PTT) activates cytotoxic T lymphocytes and reverses the immunogenic “cold” tumor microenvironment. Further, to amplify the thermal sensitivity of tumor cells, glucose oxidase (GOx) is introduced to suppress the production of heat shock proteins, thereby promoting mild photothermal therapy. Complementarily, AuPtAg nanozymes with catalase‐like activity can ameliorate tumor hypoxia, significantly improving the GOx activity. As a result, the combination of AuPtAg‐GOx with self‐augmented photothermal ability and PD‐L1 antibody can further escalate the antitumor efficacy. The AuPtAg‐GOx‐based synergistic starvation therapy, mild PTT, and immunotherapy cascade enhancement therapy strategy can be a favorable tool to effectively kill cancer cells.

Abstract Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon–carbon π-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation. In this review, we discussed the regulation of lysine crotonylation by enzymatic and non-enzymatic mechanisms, the recognition of substrate proteins, the physiological functions of lysine crotonylation and its cross-talk with other types of modification. The tools and methods for prediction and detection of lysine crotonylation were also described.

Increasing evidence indicates that neuroinflammation contributes to and exacerbates the pathogenesis of Alzheimer’s disease (AD). Neuroinflammation is thought to be primarily driven by glial cells (microglia and astrocytes) and escalates with neurodegenerative progression in AD. However, the spatiotemporal change patterns of glial reactivity and neuroinflammatory response during different stages of neurodegeneration, especially early in disease, remain unknown. Here we found that gliosis and the up-regulation of substantial neuroinflammatory genes were primarily initiated in the cortex of presenilin 1/2 conditional double knockout (cDKO) mice, rather than in the hippocampus. Specifically, astrocyte activation preceding microglial activation was found in the somatosensory cortex (SS) of cDKO mice at 6 weeks of age. Over time, both astrocyte and microglial activation were found in the whole cortex, and age-related increases in gliosis activation were more pronounced in the cortex compared to hippocampus. Moreover, the age-associated increase in glial activation was accompanied by a gradual increase in the expression of cell chemokines Ccl3 and Ccl4, complement related factors C1qb, C3 and C4, and lysosomal proteases cathepsin S and Z. These findings suggest that astrocyte and microglial activation with a concurrent increase in inflammatory mediators such as chemokines might be an early event and contribute to the pathogenesis of neurodegeneration due to presenilin deficiency.

Xuanfei Baidu granule (XFBD) is a recommended patented drug for the prevention and treatment of Corona Virus Disease 2019 (COVID-19), which is approved by the National Medical Products Administration. XFBD suppresses the over-activated immune response caused by inflammatory factor storms in COVID-19 infection. The intestine plays a crucial role in the immune system. The mass spectrometry based fecal metabolomics with 16S rDNA sequencing were combined to evaluate the effects of XFBD on host metabolism and gut microbiome. Short-chain fatty acids (SCFAs) contents in fecal matter were quantified by gas chromatography-mass spectrometry (GC-MS). Plasma samples were used to detect immune and inflammatory levels. The results were verified with a rat model of intestinal disorder. Results indicated that XFBD could increase the immune level of Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) (p < 0.05). The OPLS-DA analysis results showed that a total of 271 differential metabolites (178 up-regulated and 93 down-regulated) were identified based on the VIP ≥1, p < 0.05, FC ≥ 2 and FC ≤ 0.5. The metabolic pathways mainly involved D-Glutamine and D-glutamate metabolism, Arginine biosynthesis, Biotin metabolism, et al. XFBD modified the gut bacteria structure according to the principal component analysis (PCA), that is, 2 phyla, 3 classes, 5 orders, 11 families and 14 genera were significantly different based on taxonomic assignment. In addition, it could partially callback the relative abundance of intestinal microflora in bacterial disorder rats caused by antibiotics. It is suggested that the intervention mechanism of XFBD might be related to the regulation of intestinal flora composition. The evidence obtained in the study provides a useful reference for understanding the mechanism of XFBD.

BackgroundThe identification of high-risk population patients is key to the personalized treatment options for the stage II colorectal cancers. The use of proteomics in the prognosis of patients with stage II colorectal cancer remains unclear.MethodsUsing quantitative proteomics, we analyzed proteins that are differentially expressed in the tumor and adjacent normal tissues of 11 paired colorectal cancer patients with and without recurrence selected by a nested case-control design. Of the 21 identified proteins, we selected one candidate protein. The association of the corresponding gene of the selected protein with overall survival (OS) and adjuvant chemotherapy was analyzed using two independent cohorts of patients with stages II colorectal cancer.ResultsSterile α motif and histidine-aspartate domain-containing protein 1 (SAMHD1) was selected as the candidate biomarker. A group of 124 patients (12.5%) were stratified into SAMHD1-high subgroup. The 5-year OS rate of SAMHD1-high patients was lower than that of SAMHD1-low patients with stage II colorectal cancer (discovery cohort: hazard ratio [HR] = 2.89, 95% confidence interval [CI], 1.17-7.18, P = 0.016; validation cohort: HR = 2.25, 95% CI, 1.17-4.34, P = 0.013). The Cox multivariate analysis yielded similar results. In a pooled database, the 5-year OS rate was significantly different between patients with and without adjuvant chemotherapy among stage II SAMHD1-low tumors than in patients with stage II SAMHD1-high tumors (88% vs. 77%, P = 0.032).ConclusionsSAMHD1-high expression could help in identifying patients with stage II colorectal cancer with poor prognosis and less benefit from adjuvant chemotherapy.

Objectives: Bronchopleural fistula is a serious complication of pneumonectomy and lobectomy and results in a reduction in the quality of life of patients. This study aimed to evaluate the efficacy and safety of percutaneous drainage tube placement with continuous negative pressure drainage for the treatment of peripheral bronchopleural fistula. Methods: Data of 16 patients with peripheral bronchopleural fistula were retrospectively analyzed. A percutaneous thoracic drainage tube was placed under fluoroscopy and connected with a negative pressure suction device. The drainage tube was removed when the residual cavity disappeared on computed tomography. Results: All 16 patients underwent lobectomy, including 11 patients with lung cancer (68.8%), 4 patients with pulmonary infection (25.0%), and 1 patient with hemoptysis (6.3%). All patients underwent successful drainage tube placement on the first attempt with a technical success rate of 100%. No serious complications occurred during or after the procedure. The drainage tubes were adjusted 3.25 ± 2.24 times (range: 1–8 times). A total of 30 drainage tubes were used (average per patient, 1.88 ± 1.36 tubes). The cure time of 16 patients was 114.94 ± 101.08 days (range, 30–354 days). The median drainage tube indwelling duration was 87 days, and the 75th percentile was 117 days. Conclusion: Interventional percutaneous thoracic drainage tube placement with continuous negative pressure drainage is an effective, safe, and feasible method for the treatment of peripheral bronchopleural fistula.

Genital herpes is a common sexually transmitted disease mainly caused by herpes simplex virus type 2 (HSV-2), which can increase the risk of HIV transmission and is a major health problem in the world. Thus, it is of great significance to develop new anti-HSV-2 drugs with high efficiency and low toxicity. In this study, the anti-HSV-2 activities of PSSD, a marine sulfated polysaccharide, was deeply explored both in vitro and in vivo. The results showed that PSSD had marked anti-HSV-2 activities in vitro with low cytotoxicity. PSSD can directly interact with virus particles to inhibit the adsorption of virus to the cell surface. PSSD may also interact with virus surface glycoproteins to block virus-induced membrane fusion. Importantly, PSSD can significantly attenuate the symptoms of genital herpes and weight loss in mice after gel smear treatment, as well as reducing the titer of virus shedding in the reproductive tract of mice, superior to the effect of acyclovir. In summary, the marine polysaccharide PSSD possesses anti-HSV-2 effects both in vitro and in vivo, and has potential to be developed into a novel anti-genital herpes agent in the future.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.

The development of nanosystems, which can photooxygenate amyloid-β (Aβ), detect the Tau protein, and inhibit effectively the Tau aggregation, is increasingly important in the diagnosis and therapy of Alzheimer’s disease (AD). Herein, UCNPs-LMB/VQIVYK (UCNPs: upconversion nanoparticles, LMB: Leucomethylene blue, and VQIVYK: Biocompatible peptide) is designed as a HOCl-controlled released nanosystem for AD synergistic treatment. Under exposure to high levels of HOCl, the released MB from UCNPs-LMB/VQIVYK will produce singlet oxygen (1O2) under red light to depolymerize Aβ aggregation and reduce cytotoxicity. Meanwhile, UCNPs-LMB/VQIVYK can act as an inhibitor to decrease Tau-induced neurotoxicity. Besides, UCNPs-LMB/VQIVYK can be used for upconversion luminescence (UCL) due to its unexceptionable luminescence properties. This HOCl-responsive nanosystem offers a new therapy for AD treatment.

Nanoscale zero-valent iron (nZVI) and sulfides have been confirmed to be effective in arsenic sequestration from aqueous solution. In this study, attapulgite supported and sulfide-modified nanoscale zero-valent iron (S-nZVI@ATP) are synthesized to realize the superposition effect of enhanced arsenic sequestration. The results indicated that nZVI clusters were well disaggregated and the BET specific surface area increased from 19.61 m2·g−1 to 46.04 m2·g−1 of S-nZVI@ATP, resulting in an enhanced removal efficiency of arsenic from 51.4% to 65.1% at 20 min. The sulfides in S-nZVI@ATP mainly exist as mackinawite (FeS) and this causes the spherical nanoparticles to exhibit a larger average particle size (94.6 nm) compared to bare nZVI (66.0 nm). In addition, S-nZVI@ATP exhibited a prominent ability for arsenic sequestration over a wide pH range of 3.0–6.0. The presence of anions SO42− and Cl− can enhance the arsenic removal whereas HCO3− inhibited it. The arsenic adsorption by S-nZVI@ATP could be explained by the pseudo-second-order kinetic model and the Langmuir model, with the maximum adsorption capacity of 193.8 mg·g−1. The mechanism of As(III) sequestration by S-nZVI@ATP involved multiple processes, mainly including precipitation conversion from FeS to As2S3, surface-complexation adsorption and co-precipitation. HIGHLIGHTS S-nZVI@ATP was synthesized to superimpose the performance of nZVI and sulfides on arsenic removal.; The distribution of sulfides in S-nZVI@ATP and its role for As(III) removal were investigated.; S-nZVI@ATP showed an enlarged specific surface area and an enhanced arsenic removal efficiency.; The maximum adsorption capacity for arsenic was 193.8 mg·g−1.; The mechanism involved the combined action of Fe(0) core and sulfide shell.;

All forms of life have absolute request for metal elements, because metal elements are instrumental in various fundamental processes. Fluorescent probes have been widely used due to their ease of operation, good selectivity, high spatial and temporal resolution, and high sensitivity. In this paper, the research progress of various metal ion (Fe3+,Fe2+,Cu2+,Zn2+,Hg2+,Pb2+,Cd2+) fluorescent probes in recent years has been reviewed, and the fluorescence probes prepared with different structures and materials in different environments are introduced. It is of great significance to improve the sensing performance on metal ions. This research has a wide prospect in the application fields of fluorescence sensing, quantitative analysis, biomedicine and so on. This paper discusses about the development and applications of metal fluorescent probes in future.

Many existing refactoring tools reduce the possibility of lock conflicts and improve the concurrency of the system by reducing lock granularity and narrowing the scope of locked objects. However, such refactorings can lead to changes in concurrent program behavior, introduce concurrency errors, and often even produce code that does not compile or can be compiled but has changed semantics. To address the problem of changes in concurrent program behavior caused by transferring from coarse-grained locking to fine-grained lock refactoring, a refactoring consistency validation method for fine-grained locking is proposed. Firstly, the types of behavioral changes caused by the existing refactoring engine are analyzed in terms of thread interactions. Secondly, the relevant consistency checking rules are summarized according to the types. Finally, with the help of various program analysis techniques such as call graph analysis, alias analysis and side-effect analysis, the corresponding checking algorithms are designed according to the consistency checking rules to check the consistency of the program before and after refactoring. We implement an automatic validation tool as an Eclipse plug-in. Our approach is verified by ten open-source projects including HSQLDB, Xalan and Cassandra, etc. A total of 1,483 refactoring methods were tested, and 60 inconsistent synchronization behaviors were found, which improved the robustness of refactoring in terms of data dependence and execution order.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS–5) and its N-acetylated derivative (N–5) showed the best protective activity. Pretreatment with COS–5 or N–5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N–5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.