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Background and purposeThough hypertension disorders of pregnancy (HDP) are recognized as independent pregnancy-associated stroke risk factors, few studies have considered their impact on stroke prognosis. Therefore, we intended to evaluate the impact of HDP on short- and long-term outcomes of pregnancy-associated hemorrhagic stroke (HS).MethodsWe conducted a retrospective analysis of patients admitted to our hospital from May 2009 to December 2021 with a diagnosis of pregnancy-associated HS. After dividing patients into two groups by the presence of a diagnosis of HDP or not, the short- (at the time of discharge) and long-term (after discharge follow-up) outcomes were compared by mRS (modified Rankin Scale) scores, and poor functional outcome defined as mRS > 2. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported.ResultsTwenty-two HDP and 72 non-HDP pregnancy-associated HS patients were enrolled and follow-up after 4.7 ± 3.6 years. There was no significant difference between the two groups regarding short-term outcomes, but patients with HDP were more likely to reach poor functional outcomes at long-term follow-up (aOR = 4.47, 95% CI = 1.28–15.67, p = 0.019).ConclusionsIn this retrospective study, women with hypertension disorders of pregnancy did not show worse short-term outcomes of pregnancy-associated hemorrhagic stroke compared to those without but had poorer long-term functional outcomes. This underlines the importance of prevention, recognition, and treatment of hypertension disorders in these women.

Abstract Although immunotherapy has achieved recent clinical success in antitumor therapy, it is less effective for solid tumors with large burdens. To overcome this challenge, herein, we report a new strategy based on platelet membrane‐camouflaged aggregation‐induced emission (AIE) luminogen (Plt‐M@P) combined with the anti‐programmed death ligand 1 (anti‐PD‐L1) for tumoral photodynamic‐immunotherapy. Plt‐M@P is prepared by using poly lactic‐co‐glycolic acid (PLGA)/PF3‐PPh3 complex as a nanocore, and then by co‐extrusion with platelet membranes. PF3‐PPh3 is an AIE‐active conjugated polyelectrolyte with photosensitizing capability for photodynamic therapy (PDT). Plt‐M@P exhibits superior tumor targeting capacity in vivo. When applied in small tumor‐bearing (~40 mm3) mice, Plt‐M@P‐mediated PDT significantly inhibits tumor growth. In tumor models with large burdens (~200 mm3), using Plt‐M@P‐mediated PDT or anti‐PD‐L1 alone is less effective, but the combination of both is effective in inhibiting tumor growth. Importantly, this combination therapy has good biocompatibility, as demonstrated by the absence of damage to the major organs, especially the reproductive system. In conclusion, we show that Plt‐M@P‐mediated PDT can improve anti‐PD‐L1 immunotherapy by enhancing antitumor effects, providing a promising strategy for the treatment of tumors with large burdens.

BackgroundThe wave of education information based on the “Internet+” has swept the world, and the traditional teaching mode can no longer meet the new needs of education teaching, so the teaching mode of “MOOC+ flipped classroom” has attracted widespread attention educators.ObjectiveThis study explores the effect of “MOOC+ flipped classroom” on the teaching design and application of basketball courses in colleges and universities from the perspective of education modernization in order to promote the development of students’ core literacy and provide a more theoretical basis and practical support for the in-depth research and promotion of “MOOC+ flipped classroom” teaching mode.MethodsThis study adopts a quasi-experimental design to study the teaching of basketball courses in colleges and universities based on “MOOC +flipped classroom.” The experimental class adopted “MOOC+ flipped classroom” teaching (34 students), and the control group adopted traditional classroom teaching (30 students). Before and after the 16-week intervention, the student’s learning effects were measured by basketball skill level assessment, Cooperation Ability Scale for University Students, Utrecht Work Engagement Scale-student, and Self-regulated Learning Scale, and the data were analyzed by independent sample t-test and repeated-measures ANOVA.Conclusion(1) Compared with the traditional classroom teaching mode, the “MOOC+ flipped Classroom” teaching mode is innovative in terms of teaching philosophy, teaching resources, and teaching methods, which promotes the change of education informatization and further promotes the realization of education modernization. (2) The “MOOC+ flipped classroom”-based teaching design for basketball courses benefits students’ basketball skill level, study engagement, cooperation ability, and self-regulated learning ability, thus effectively promoting the students’ core literacy.

BackgroundThe predictive effects of liver metastases for immune-checkpoint inhibitors (ICIs) and the relationship between tumor mutational burden (TMB) and liver metastases (LM) remain unclear.MethodsA systematic review and meta-analysis were conducted to explore the heterogeneity of ICIs efficacy between patients with or without LM. A pan-cancer cohort of 1,661 patients who received ICIs was downloaded and analyzed to assess the association between TMB and LM.ResultsOf 21053 studies identified in our search, eight single-arm studies and 24 randomized controlled trials were included. Overall, 17957 patients with advanced or metastatic cancers (4805 patients (26.8%) with LM and 13151 patients (73.2%) without LM) were enrolled. The pooled objective response rate (ORR) was 8.5% (95% CI 4%–13%) in the LM group versus 21% (95% CI 16%–21%) in the non-LM group. The pooled hazard ratio (HR) for death was 0.85 (95% CI 0.80–0.90) in the LM group treated with ICIs compared with the standard of care. In patients without LM who were treated with ICIs, the pooled HR for death was 0.78 (95% CI 0.73–0.82) compared with the standard of care. The difference in efficacy between patients with or without LM treated with ICIs was significant (p=0.04). Pan-cancer analysis revealed that the TMB-high rate was 10.8% in liver metastatic lesions versus 21.4% in other metastatic lesions (p=0.004). In addition, TMB was also significantly associated with OS as a binary cutoff (p=0.05) and was an independent prognostic variable (HR=0.98, P=0.047) as a continuous variable in patients with LM.ConclusionsIn patients with LM, the efficacy of immunotherapy was attenuated, but TMB-high could predict better survival outcomes.

ObjectiveTo assess the outcome of a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering (BFIC) for the single-stage repair of severe hypospadias in children.Materials and methodsA retrospective study was performed on 40 children with hypospadias who were treated in our hospital from December 2017 to February 2022. The inclusion criteria were as follows: (1) the patient had proximal hypospadias, or penile curvature over 30° after degloving the penis; and (2) the patient underwent surgery for hypospadias for the first time. A free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering was performed, and all patients were followed up for more than 6 months.ResultsAfter degloving the foreskin, the urethral orifice was retracted to the perineum and scrotum in 20 cases, penoscrotal in 8 cases, and penile in 12 cases. Single-stage repair was achieved without complications in 34 (85%) patients. The remaining six patients experienced postoperative complications: urethrocutaneous fistula occurred in five cases and glans dehiscence with urethrocutaneous fistula in one case. No urethral diverticulum occurred in any case. A neomeatus with a vertically oriented slit-like appearance was achieved at the tip of the glans in all cases, with one exception.ConclusionThe single-stage operation with a free preputial tube graft coupled with urethral plate urethroplasty combined with a Buck's fascia integral covering in the treatment of severe hypospadias achieves favorable functional and cosmetic outcomes.

Abstract Background For patients with locally advanced (T3-4/N +) rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with total mesorectal resection, which greatly decreases local recurrence but does not improve overall survival. For patients who achieve a complete clinical response (cCR) after nCRT, a “Watch & Wait” (W&W) approach can be received to improve quality of life. Currently, total neoadjuvant therapy (TNT) has been demonstrated to increase the complete response rate and achieve early control of distant metastasis. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and radiotherapy. Thus, for LARC patients, the combination of immunotherapy and TNT is likely to further improve the rate of complete response and prognosis. The disparities between induction therapy and consolidation therapy need to be investigated. Methods TORCH is a randomized, prospective, multicentre, double-arm, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy in LARC. 130 LARC patients will be treated with the TNT approach and assigned to the consolidation arm and induction arm. The consolidation arm will receive SCRT, followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) and Toripalimab. The induction arm will first receive 2 cycles of CAPOX and Toripalimab, then receive SCRT, followed by 4 cycles of CAPOX and Toripalimab. Both groups will receive curative surgery or the W&W strategy. The primary endpoint is the complete response rate (rate of pCR plus cCR). The secondary endpoints include the grade 3–4 acute adverse effects rate, 3-year disease-free survival (DFS) rate, 3-year local recurrence-free survival (LRFS) rate, 3-year OS rate, rate of surgical complications and quality of life (QoL) scores. The “pick the winner” method is used to investigate the better treatment regimen. The trial was opened on 13th April 2021, and the first patient was recruited on 6th May 2021. Discussion TORCH will investigate whether SCRT combined with chemotherapy and Toripalimab can achieve better complete response rates, good tolerance and prognosis in LARC patients. This is the first clinical trial to compare the efficacy of induced immunotherapy and consolidative immunotherapy based on the TNT strategy. Trial registration Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT04518280 , August 15, 2020.

We performed a retrospective, observational study of 51 eyes in 51 treatment-naïve patients with polypoidal choroidal vasculopathy (PCV), whose lesion ranged within the 6 × 6 mm scope of optical coherence tomography angiography (OCTA). The patients were divided into an ill-defined group and a well-defined group based on the pattern of branching vascular network (BVN) on OCTA. BVN morphology was not related to baseline best-corrected visual acuity (BCVA). However, the BCVA in the ill-defined BVN group (−0.18 [interquartile range: −0.40 to 0.00]) was significantly improved after anti-vascular endothelial growth factor (VEGF) injections, compared with that (0.00 [interquartile range: −0.18 to 0.00]) in the well-defined group (z = 2.143, p = 0.032). Multiple logistic regression analysis showed that male sex, fewer injections, and the presence of polypoidal lesions on OCTA images at baseline predicted a poor prognosis in patients with polypoidal lesions on OCTA images after anti-VEGF therapy (all p < 0.05). Finally, BCVA at baseline and the number of injections were protective factors for BCVA after anti-VEGF therapy (all p < 0.05). In contrast, a history of hypertension and macular edema at baseline were risk factors for BCVA after anti-VEGF injections (all p < 0.05). Our results revealed the visual and morphological prognosis of patients with active subfoveal circumscribed PCV after anti-VEGF therapy.

The diagnosis of ewes’ pregnancy status at an early stage is an efficient way to enhance the reproductive output of sheep and allow producers to optimize production and management. The techniques of proteomics and metabolomics have been widely used to detect regulatory factors in various physiological processes of animals. The aim of this study is to explore the differential metabolites and proteins in the serum of pregnant and non-pregnant ewes by proteomics and metabolomics. The serum of ewes at 21, 28 and 33 days after artificial insemination (AI) were collected. The pregnancy stratus of the ewes was finally determined through ultrasound examination and then the ewes were grouped as Pregnant (n = 21) or N on-pregnant (n = 9). First, the serum samples from pregnant or non-pregnant ewes at 21 days after AI were selected for metabolomic analysis. It was found that the level of nine metabolites were upregulated and 20 metabolites were downregulated in the pregnant animals (p < 0.05). None of these differential metabolomes are suitable as markers of pregnancy due to their small foldchange. Next, the proteomes of serum from pregnant or non-pregnant ewes were evaluated. At 21 days after AI, the presence of 321 proteins were detected, and we found that the level of three proteins were upregulated and 11 proteins were downregulated in the serum of pregnant ewes (p < 0.05). The levels of serum amyloid A (SAA), afamin (AFM), serpin family A member 6 (SERPINA6) and immunoglobulin-like domain-containing protein between pregnant and non-pregnant ewes at 21-, 28- and 33-days post-AI were also analyzed via enzyme-linked immunosorbent assay (ELISA). The levels of SAA and AFM were significantly higher in pregnant ewes than in non-pregnant ewes, and could be used as markers for early pregnancy detection. Overall, our results show that SAA and AFM are potential biomarkers to determine the early pregnancy status of ewes.

PurposeTo analyze the safety and feasibility of computed tomography (CT)-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy.MethodsThe data of 431 patients with 540 lung nodules undergoing CT-guided biopsy or ablation were retrospectively analyzed. Biopsy-only group (A): 107 patients (107 lesions) received CT-guided percutaneous lung biopsy only; Ablation-only group (B): 117 cases (117 lesions) only received CT-guided thermal ablation; Single focal ablation combined with biopsy group (C): 103 patients (103 lesions) received CT-guided thermal ablation combined with intraoperative immediate biopsy; Multifocal ablation combined with biopsy group (D): 104 patients (213 lesions) received CT-guided thermal ablation combined with intraoperative biopsy. The success rate of this technique was calculated, the complications were recorded, and the positive rate of pathological diagnosis of the specimens was evaluated (the tissue specimens could be confirmed as positive by pathological diagnosis).ResultsAll 431 patients with pulmonary nodules successfully completed the operation, and the technical success rate was 100% (431/431). In group A, hemoptysis occurred in seven cases after operation, while no hemoptysis was observed in the other groups. Pneumothorax occurred in 8 cases in group A, 14 cases in group B, 11 cases in group C, and 13 cases in group D. Hydrothorax occurred in 4 cases in group A, 7 cases in group B, 5 cases in group C and 9 cases in group D, and there were no significant differences between the groups. The positive rate of pathological diagnosis was 84.1% (90/107) in group A, 81.5% (84/103) in group C, and 82.6% (176/213) in group D, and there was no significant difference among the groups (P > 0.05). A total of 15 cases in group C and 23 cases in group D underwent gene testing and analysis, and the biopsy tissue samples all met quality control standards.ConclusionCT-guided thermal ablation of multiple pulmonary nodules combined with intraoperative biopsy does not prolong the length of hospital stay or increase the risk of postoperative complications. It can meet the requirements of clinical, pathological and genetic testing, and is safe and reliable.

For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of ‘Watch and Wait (W&W)’ approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis.

The traditional enzyme-linked immunosorbent assay has been widely applied in the field of protein detection. Nevertheless, the detecting performance suffers from high background. Herein, we choose label free molecules of aggregation-induced emission (AIE) to design DNA supersandwich immunoassay (DSI) for ultrasensitive α-fetoprotein (AFP) detection. The silole-R, typical water soluble AIEgens (fluorogen with AIE feature) with positive charges, adsorbs on phosphate backbone of DSI by electrostatic attraction. In this way, the AIEgens DSI allows for ultrasensitive detecting AFP with low limit of detection (1.4 ng/mL). Moreover, the AIEgens DSI demonstrates a higher signal-to-background ratio (10.94) than fluorescein isothiocyanate (FITC) DSI (4.38). This AIEgens DSI provides a novel fluorescent enhanced analysis of trace AFP for cancer diagnose.

Purpose Hepaticojejunostomy anastomosis (HJA) is the most challenging aspect in single-port laparoscopic choledochal cystectomy and Roux-en-Y hepaticojejunostomy (SPCH) in children, especially in small-diameter anastomoses (diameters less than 5 mm), which are more susceptible to anastomotic stricture. We developed the continuous submucosal technique for HJA (CS-HJA) to lessen postoperative complications. The purpose of this study is to introduce our preliminary experiences with CS-HJA. Methods We retrospectively analyzed all available clinical data of children who underwent SPCH surgery between March 2020 and October 2022. We operated with CS-HJA on 10 children who were diagnosed with small-diameter hepaticojejunostomy (diameter less than 5 mm). Data collection mainly included demographic information, imaging data, perioperative details, and postoperative outcomes. Ten patients were included in this study. The average patient age was 55.2 months; the age range was 3 to 120 months, and the average weight was 11.6 kg; male–female ratio was 1:9. The choledocho had fusiform dilatation in five cases and cystic dilatation in five cases. There was no dilatation of the left and right hepatic ducts or intrahepatic bile ducts in all patients. All patients had no dilatation of the left and right hepatic ducts or intrahepatic bile ducts. All patients underwent a single-port laparoscopic bile-intestinal anastomosis using a submucosal jejunal anastomosis technique. Analysis of the duration of the bile-intestinal anastomosis, the length of the child's stay in the hospital after surgery, the intraoperative complications, and the postoperative complications was performed. Results All the 10 patients underwent successful SPCH by CS-HJA technique. The average length of time for hepaticojejunostomy ranged from 22 to 40 minutes, and the postoperative hospital stay was 5.2 to 9.2 days. There were no instances of bile leakage following the operation. At 17 to 30 months of follow-up, there was no abdominal pain or jaundice, and the reexamination of transaminases, bilirubin, and amylase were normal. Ultrasonography showed no bile duct stricture or dilated bile ducts, and the incision is elegant, and the families of the patients were satisfied. Conclusion In SPCH surgery in children, the CS-HJA technique is safe and feasible for small-diameter hepaticojejunostomy. [ABSTRACT FROM AUTHOR]

Ent-kaurane diterpene compounds have attracted considerable attention in recent years due to its antitumor, antibacterial, and antiviral activities. However, the clinical development of natural kaurane diterpenes, for example, oridonin for cancer therapy has been hampered by its relatively moderate potency, limited bioavailability. Herein, we report a newly synthetic analog of natural ent-kaurane diterpene, DS2, which exhibits significantly improved activity of antiproliferation against various cancer cell lines relative to oridonin. DS2 treatment triggers the mitochondria-mediated apoptosis and cell cycle arrest in human esophageal cancer cell lines (EC9706, EC109). Interestingly, normal human esophageal epithelial cells (HEECs) and normal human liver cells (HL-7702) are both significantly more resistant to the growth inhibition by DS2 compared with esophageal cancer cells. The DS2-induced apoptosis in EC9706 cells correlated with the drop of mitochondrial membrane potential (MMP), release of cytochrome c into the cytosol and activation of caspase-9 and -3. The induction of proapoptotic proteins p21 and Bax were also observed in DS2-treated cells. The DS2-induced apoptosis was significantly attenuated by knockdown of Bax proteins. Meanwhile, the DS2 treatment caused generation of reactive oxygen species (ROS) in human esophageal cancer cells, but not in HEECs, which was attenuated by pretreatment with ROS scavenger N-acetylcysteine (NAC). More interestingly, the antioxidants pretreatment completely attenuated DS2 mediated loss of the MMP and apoptosis, as well as Bax expression and growth inhibition. In conclusion, the present study reveals that the mitochondria-mediated cell death by DS2 is associated with Bax regulation and ROS generation, and understanding the function and mechanism of DS2 will help us to design better anti-cancer drugs.

Alisol B 23-Acetate (AB23A) is a naturally occurring triterpenoid, which can be indicated in the rhizome of medicinal and dietary plants from Alisma species. Previous studies have demonstrated that AB23A could inhibit intestinal permeability by regulating tight junction (TJ)-related proteins. Even so, the AB23A protective mechanism against intestinal barrier dysfunction remains poorly understood. This investigation seeks to evaluate the AB23A protective effects on intestinal barrier dysfunction and determine the mechanisms for restoring intestinal barrier dysfunction in LPS-stimulated Caco-2 monolayers. According to our findings, AB23A attenuated the inflammation by reducing pro-inflammatory cytokines production like IL-6, TNF-α, IL-1β, and prevented the paracellular permeability by inhibiting the disruption of TJ in LPS-induced Caco-2 monolayers after treated with LPS. AB23A also inhibited LPS-induced TLR4, NOX1 overexpression and subsequent ROS generation in Caco-2 monolayers. Transfected with NOX1-specific shRNA diminished the up-regulating AB23A effect on ZO-1 and occludin expression. Moreover, transfected with shRNA of TLR4 not only enhanced ZO-1 and occludin expression but attenuated NOX1 expression and ROS generation. Therefore, AB23A ameliorates LPS-induced intestinal barrier dysfunction by inhibiting TLR4-NOX1/ROS signaling pathway in Caco-2 monolayers, suggesting that AB23A may have positive impact on maintaining the intestinal barrier’s integrity.

A novel AlGaN/GaN Super Heterojunction Field Effect Transistors (super HFET) with dual-polarization junction (DPJ) on the back-barrier layer and its working mechanism is studied. DPJ AlGaN/GaN super HEMT has two polarization junctions with an interval of 1 μm composed of a p-type GaN cap layer and an undoped GaN cap layer, which contact with the gate. In the high voltage blocking state, the two reverse p–n junctions introduced by the polarization junction will effectively modulate the surface electric field and the volume electric field. In addition, this structure suppresses the leakage current of the buffer and leads to higher breakdown voltage. The TCAD simulation results show that at the same gate–drain length of 20 μm, the breakdown voltage of the DPJ structure can be increased from about 1100 V to above 2100 V with an on-resistance of 12.86 Ωmm, slightly higher than that of conventional super HFET. The FOM of DPJ super HFET is up to 1.32 × 109V2Ω−1cm−2. It shows a better tradeoff relationship between on-resistance and breakdown voltage.

Erythrocytes are often used for the development of cell membrane camouflaged nanoparticles (NPs) due to their wide range of sources. However, whether the difference between autologous and allogeneic sources for the erythrocyte membranes have an influence on the performance of camouflaged NPs, which is still inconclusive. To this end, we developed two aggregation-induced emission (AIE) photosensitizers camouflaged with erythrocyte membranes (E-M), named E-Mauto@P and E-Mallo@P, which were prepared using autologous- and allogeneic-derived erythrocytes, respectively. In vivo, E-M@P-mediated photodynamic therapy (PDT) effectively inhibited tumor growth, and this therapeutic effect did not differ between E-Mauto@P and E-Mallo@P. Importantly, there were no differences between E-Mauto@P and E-Mallo@P treated mice in terms of general condition, organ function or immune system. Both E-Mauto@P and E-Mallo@P have been shown not to cross the placental barrier and do not affect the development of the embryo, which could be a good platform for the treatment of pregnancy-related disorders. These findings provided more detailed evidences for erythrocyte membrane camouflaged NPs as a promising therapeutic platform, since there is no difference in efficacy or biosafety of either autologous or allogeneic erythrocyte-derived NPs.

Autophagy is an evolutionarily conserved self-protecting mechanism implicated in cellular homeostasis. ATG4B plays a vital role in autophagy process via undertaking priming and delipidation of LC3. Chemical inhibitors and regulative modifications such as oxidation of ATG4B have been demonstrated to modulate autophagy function. Whether and how ATG4B could be regulated by metal ions is largely unknown. Copper is an essential trace metal served as static co-factors in redox reactions in physiology process. Excessive accumulation of copper in ATP7B mutant cells leads to pathology progression such as insoluble Mallory body (MB) in Wilson disease (WD). The clearance of MB via autophagy pathway was thought as a promising strategy for WD. Here, we discovered that copper ion instead of other ions could inhibit the activity of ATG4B followed by autophagy suppression. In addition, copper could induce ATG4B oligomers depending on cysteine oxidation which could be abolished in reduced condition. Copper also promotes the formation of insoluble ATG4B aggregates, as well as p62-and ubiquitin-positive aggregates, which is consistent with the components of MB caused by copper overload in WD cell model. Importantly, overexpression of ATG4B could partially reduce the formation of MB and rescue impaired autophagy. Taken together, our results uncovered for the first time a new damage mechanism mediated by copper and implied new insights of the crosstalk between the toxicity of copper and autophagy in the pathogenesis of WD.

Abstract. Whether a fish-rich diet is positively associated with cognitive function after stroke remains unclear; thus, the present study investigated the relationship between them. The present study was part of a prospective multicenter study, in which 920 individuals (609 males, mean age, 62.78 ± 11.79 years) were included from November 2013 to December 2015. The cognitive function of the patients was evaluated, and the diagnosis of poststroke cognitive impairment (PSCI) was made during their stay in the hospital. A subgroup of 439 patients from a single center was followed up for 4 to 6 years and was reassessed for cognitive function. According to the diagnostic criteria, the PSCI prevalence was lower in the fish-rich diet group (P

Sepsis represents a life-threatening organ dysfunction due to an aberrant host response. Of note is that majority of patients have experienced a severe immune depression during and after sepsis, which is significantly correlated with the occurrence of nosocomial infection and higher risk of in-hospital death. Nevertheless, the clinical sign of sepsis-induced immune paralysis remains highly indetectable and ambiguous. Given that, specific yet robust biomarkers for monitoring the immune functional status of septic patients are of prominent significance in clinical practice. In turn, the stratification of a subgroup of septic patients with an immunosuppressive state will greatly contribute to the implementation of personalized adjuvant immunotherapy. In this review, we comprehensively summarize the mechanism of sepsis-associated immunosuppression at the cellular level and highlight the recent advances in immune monitoring approaches targeting the functional status of both innate and adaptive immune responses.

Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman’s correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of Faecalibacteriu, Roseburia, and Fusicatenibacter decreased while the abundance of Parabacteroides and Bacteroides increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.

Large mammals can perceive humans as predators and therefore adjust their behavior to achieve coexistence with humans. However, lack of research at sites with low hunting intensity limits our understanding of how behavioral responses of animals adapt to different predation risks by humans. At Heshun County in North China, where hunting has been banned for over three decades and only low-intensity poaching exists, we exposed two large ungulates (Siberian roe deer Capreolus pygarus and wild boar Sus scrofa) to the sounds of humans, an extant predator (leopard Panthera pardus) and a control (wind), and examined their flight responses and detection probabilities when hearing different type of sounds. Both species showed higher flight probabilities when hearing human vocalization than wind, and wild boar were even more likely to flee upon hearing human vocalization than leopard roar, suggesting the behavioral response to humans can equal or exceed that of large carnivores in these two ungulates even in an area without hunting practices. Recorded sounds had no effect on detection probability of both ungulates. Additionally, with repeated exposure to sounds, regardless of treatment, roe deer were less likely to flee and wild boars were more likely to be detected, indicating a habituation-type response to sound stimuli. We speculate that the immediate flight behavior rather than shifts in habitat use of the two species reflect the low hunting/poaching pressure at our study site and suggest further examination of physiological status and demographic dynamics of the study species to understand human influence on their long-term persistence.

Instabilities in multiplies of ion cyclotron frequency range are identified and termed as core ion cyclotron emission (ICE) in recent HL-2A neutral beam injection heated experiments. Characteristics of the core ICE are presented, including frequency dependence and harmonics features. The detected frequencies are found to agree well with the multiplies of the deuterium cyclotron frequency around the magnetic axis. Additionally, the core ICE exhibits a predominantly compressional property. Observations of distinct spectrum features and individual excitation of each harmonic have demonstrated that the core ICE harmonics are independent multiple modes. Notably, the variation of plasma current is a necessary condition for exciting the 4th harmonic ICE individually. The results suggest that the drive mechanism of core ICE varies between the different frequency ranges.

The production performance and forage quality of 20 maize varieties were comprehensively evaluated from 2021 to 2022, aiming at screening out silage maize varieties suitable for planting in Anding district or similar areas. In 2021, the agronomic traits and forage yield of 20 tested maize varieties were measured, including plant height, stem diameter, leaf number, single plant weight, ear length, ear diameter, and row number per ear. The nutritional components were comprehensively analyzed by membership function method, and the tested varieties were comprehensively evaluated by combining forage relative feeding value (RFV) and forage grading index (GI). Xingzhu 88, Xianyu 1321, Zhongnongda 2118, Jingke silage 516, Jingke 968, Jingjiu silage 16, Tongkang 1, Jingke silage 932, and Xianyu 1225 were preliminarily screened. In 2022, the nine selected varieties were further comprehensively evaluated by the same method. The results showed that Jingke silage 932, Jingke silage 516, Jingjiu silage 16, and Xingzhu88 had good adaptability, excellent agronomic characters and yield, and high relative feeding value, which were suitable for popularization and planting in Anding district or similar areas. [ABSTRACT FROM AUTHOR]

A ring foundation is widely used in bridges, water towers, caissons, and other engineering structures, and its ultimate bearing capacity is one of the significant concerns in engineering design. This paper is aimed at exploring the ultimate bearing capacity of ring foundations embedded in undrained clay. Based on the finite element limit analysis, effects of the inside-to-outside radius ratio, embedment depth ratio, cutting face inclination angle, and face roughness on the vertical ultimate bearing capacity of ring foundations are investigated. The results show that the ultimate bearing capacity of the ring foundation increases gradually with the embedment depth ratio. When the embedment depth ratio D/B reaches a critical value, the bearing capacity tends to be stable, and the critical embedment depth ratio is affected by the inside-to-outside radius ratio of the ring foundation, varying from 0.2 to 0.4. The ultimate bearing capacity of the ring foundation decreases with cutting face inclination angle β. When β≤40°, the ultimate bearing capacity tends to be stable, and the bearing capacity is reduced by approximately 30%. The influence of the cutting face inclination angle on the bearing capacity is highly dependent on the roughness of the cutting face.

The Grain for Green project (GGP), initialized by the Chinese government in 1999, has achieved substantial achievements accompanied by a decrease in surface runoff on the Loess Plateau, but the impacts of large-scale afforestation on regional water resources are uncertain. Hence, the objective of this study was to explore the impact of land use change on generalized water resources and ecological water stress using the blue and green water concepts, taking the Yanhe River Basin as the case study. The Soil and Water Assessment Tool (SWAT) was applied to quantify the green water and blue water, which are defined as generalized water resources. The ecological water requirement of vegetation (forest and grass), agricultural water footprint and virtual water flow are considered regional water requirements. The land use types of 1980 (Scenario I) and 2017 (Scenario II) were entered into the SWAT model while keeping the other parameters constant to isolate the influence of land use changes. The results show that the average annual differences in blue, green and generalized water resources were -72.08 million m3, 24.34 million m3, and -47.74 million m3, respectively, when the simulation results of Scenario II were subtracted from those of Scenario I, which shows that land use change caused by the GGP led to a decrease in blue and generalized water resources and an increase in green water resources. Surface runoff in Scenario I was more than that in Scenario II in all of the years of the study period from 1980–2017, and green water storage in Scenario I was more than that in Scenario II in all of the years of the study period except in 1998; although lateral flow in Scenario I was less than that in Scenario II except in 2000 and 2015, as was groundwater runoff in 1992, 2000 and 2015, and green water flow in 1998. Blue water flow, green water storage and green water flow in Scenario II were less than those in Scenario I in the whole basin, 12.89 percent of the basin and 99.21 percent of the basin, respectively. The total water footprint increased from 1995 to 2010 because the forest water footprint increased significantly in this period, although the agricultural water footprint and grass water footprint decreased. The ecological water stress index values had no obvious temporal change trends in either land use scenario, but the ecological water stress index in Scenario II was greater than that in Scenario I, which illustrates that the GGP led to an increase in ecological water stress from the perspective of generalized water resources.