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Objectives: This study aimed to examine the relationship between measures of kidney function and impaired lung function in individuals with diabetes and to assess all-cause mortality risk associated with having chronic kidney disease (CKD) and or impaired lung function., Design: Cross-sectional and retrospective cohort study., Setting: The National Health and Nutrition Examination Survey 2007-2012., Participants: A total of 10 809 participants aged over 20 years were included in this study: 9503 with normal spirometry, 951 with preserved ratio impaired spirometry (PRISm) and 355 with variable obstruction (VO)., Exposure and Outcome Measures: Kidney function measures, including estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), were considered exposure variables. PRISm and VO were outcome variables. PRISm was defined as a forced expiratory volume in 1 s (FEV1)<80% predicted and an FEV1/forced vital capacity (FVC) ratio≥0.7, while VO was defined as an FEV1/FVC ratio <0.7 prebronchodilator and ≥0.7 postbronchodilator. In the cross-sectional analysis, multivariate logistic regression models were used to assess the relationship between kidney function measures and spirometry findings. In the retrospective cohort analysis, Cox proportional hazards models were employed to evaluate the impact of having PRISm or VO, combined with CKD, on all-cause mortality., Results: An increase in UACR was significantly associated with higher odds of PRISm (OR (95% CI)=1.10 (1.01, 1.21), p=0.03). Additionally, eGFR <60 was associated with the odds of variable obstructive lung function (OR (95% CI)=1.72 (1.07, 2.74), p=0.03) compared with eGFR >60. After adjustments, an increase in UACR was associated with higher odds of PRISm in individuals with diabetes (OR (95% CI)=1.21 (1.08, 1.36), p=0.002), and UACR ≥300 mg/g significantly increased odds of having PRISm in idividuals with diabetes (OR (95% CI)=2.34 (1.23, 4.47), p=0.01). During a mean follow-up of 12.3 years, 10 500 deaths occurred. In the diabetic group, compared with normal spirometry without CKD, those with both PRISm and CKD had a significantly increased risk of all-cause mortality (HR (95% CI)=3.46 (1.94, 6.16), p<0.0001)., Conclusion: An elevated UACR and albuminuria were linked to a higher risk of PRISm. Our study emphasises that kidney and lung function are correlated. Further research is necessary to confirm our findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Copper, a vital trace element, is indispensable for the maintenance of physiological functioning, particularly in the cardiac system. Unlike other forms of cell death such as iron death and apoptosis, copper‑induced cell death has gained increasing recognition as a significant process influencing the development of cardiovascular diseases. The present review highlights the significance of maintaining copper homeostasis in addressing cardiovascular diseases. This review delves into the crucial roles of copper in physiology, including the metabolic pathways and its absorption, transport and excretion. It provides detailed insights into the mechanisms underlying cardiovascular diseases resulting from both excess and deficient copper levels. Additionally, it summarizes strategies for treating copper imbalances through approaches such as copper chelators and ion carriers while discussing their limitations and future prospects.

Catalytic CO 2 reduction poses a significant challenge for the conversion of CO 2 into chemicals and fuels. Ni-Fe carbon monoxide dehydrogenase ([NiFe]-CODH) effectively mediates the reversible conversion of CO 2 and CO at a nearly thermodynamic equilibrium potential, highlighting the heterobimetallic cooperation for the design of CO 2 reduction catalysts. However, numerous NiFe biomimetic model complexes have realized little success in CO 2 reduction catalysis, which underscores the crucial role of precise bimetallic configuration and functionality. Herein, we presented a heterobimetallic NiFe complex for the photocatalytic reduction of CO 2 to CO, demonstrating significantly enhanced catalytic performance compared to the homonuclear NiNi catalyst. Photocatalytic and mechanistic investigations revealed that with the assistance of a redox-active phenanthroline ligand, NiFe achieves dual-site activation of CO 2 through a pivotal intermediate, Ni II (μ-CO 2 2- -κC:κO)Fe II , where the Lewis acidity of the Fe II site plays an important role, as corroborated in the homonuclear FeFe system. This study introduces the first heteronuclear NiFe molecular catalyst capable of efficiently catalyzing the reduction of CO 2 to CO, deepening insights into heterobimetallic cooperation and offering a novel strategy for designing highly active and selective CO 2 reduction catalysts.

The current throughput of conventional organic chemical synthesis is usually a few experiments for each operator per day. We develop a robotic system for ultra-high-throughput chemical synthesis, online characterization, and large-scale condition screening of photocatalytic reactions, based on the liquid-core waveguide, microfluidic liquid-handling, and artificial intelligence techniques. The system is capable of performing automated reactant mixture preparation, changing, introduction, ultra-fast photocatalytic reactions in seconds, online spectroscopic detection of the reaction product, and screening of different reaction conditions. We apply the system in large-scale screening of 12,000 reaction conditions of a photocatalytic [2 + 2] cycloaddition reaction including multiple continuous and discrete variables, reaching an ultra-high throughput up to 10,000 reaction conditions per day. Based on the data, AI-assisted cross-substrate/photocatalyst prediction is conducted., (© 2024. The Author(s).)

Background: Biliary atresia (BA) is a devastating neonatal cholangiopathy with an unclear pathogenesis, and prompt diagnosis of BA is currently challenging., Methods: Proteomic and immunoassay analyses were performed with serum samples from 250 patients to find potential BA biomarkers. The expression features of polymeric immunoglobulin receptor (PIGR) were investigated using human biopsy samples, three different experimental mouse models, and cultured human biliary epithelial cells (BECs). Chemically modified small interfering RNA and adenovirus expression vector were applied for in vivo silencing and overexpressing PIGR in a rotavirus-induced BA mouse model. Luminex-based multiplex cytokine assays and RNA sequencing were used to explore the molecular mechanism of PIGR involvement in the BA pathogenesis., Findings: Serum levels of PIGR, poliovirus receptor (PVR), and aldolase B (ALDOB) were increased in BA patients and accurately distinguished BA from infantile hepatitis syndrome (IHS). Combined PIGR and PVR analysis distinguished BA from IHS with an area under the receiver operating characteristic curve of 0.968 and an accuracy of 0.935. PIGR expression was upregulated in the biliary epithelium of BA patients; Th1 cytokines TNF-α and IFN-γ induced PIGR expression in BECs via activating NF-κB pathway. Silencing PIGR alleviated symptoms, reduced IL-33 expression, and restrained hepatic Th2 inflammation in BA mouse model; while overexpressing PIGR increased liver fibrosis and IL-33 expression, and boosted hepatic Th2 inflammation in BA mouse model. PIGR expression promotes the proliferation and epithelial-mesenchymal transition, and reduced the apoptosis of BECs., Interpretation: PIGR participated in BA pathogenesis by promoting hepatic Th2 inflammation via increasing cholangiocytes derived IL-33; PIGR has the value as a diagnostic and therapeutic biomarker of BA., Funding: This study was financially supported by the National Natural Science Foundation of China (82170529), the National Key R&D Program (2021YFC2701003), and the National Natural Science Foundation of China (82272022)., Competing Interests: Declaration of interests The authors do not have any disclosures to report., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Antagonistic bacterial strains from Bacillus spp. have been widely studied and utilized in the biocontrol of phytopathogens and the promotion of plant growth, but their impacts on the rhizosphere microecology when applied to crop plants are unclear. Herein, the effects of applying the antagonistic bacterium Bacillus subtilis S1 as a biofertilizer on the rhizosphere microecology of cucumbers were investigated. In a pot experiment on cucumber seedlings inoculated with S1, 3124 bacterial operational taxonomic units (OTUs) were obtained from the rhizosphere soils using high-throughput sequencing of 16S rRNA gene amplicons, and the most abundant phylum was Proteobacteria that accounted for 49.48% in the bacterial community. S1 treatment significantly reduced the abundances of soil bacterial taxa during a period of approximately 30 days but did not affect bacterial diversity in the rhizosphere soils of cucumbers. The enzymatic activities of soil nitrite reductase (S-Nir) and dehydrogenase (S-DHA) were significantly increased after S1 fertilization. However, the activities of soil urease (S-UE), cellulase (S-CL), and sucrase (S-SC) were significantly reduced compared to the control group. Additionally, the ammonium- and nitrate-nitrogen contents of S1-treated soil samples were significantly lower than those of the control group. S1 fertilization reshaped the rhizosphere soil bacterial community of cucumber plants. The S-CL activity and nitrate-nitrogen content in rhizosphere soil affected by S1 inoculation play important roles in altering the abundance of rhizosphere soil microbiota., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson's disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep-wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2-10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences., (© 2024. The Author(s).)

Objective: To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury., Methods: From January 2016 to December 2020, the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed, including 35 males and 22 females, aged from 18 to 47 years old with an average of (32.9±7.9) years old. Knee function was evaluated using the International Knee Documentation Committee (IKDC) and Lysholm scores both before the operation and at the final follow-up. Meniscus healing was evaluated according to the postoperative Barrett standard. Wound healing complications, such as vascular injury, nerve injury, and lower extremity venous thrombosis, were recorded., Results: All 57 patients were followed up for 12 to 58 months with an average of (38.1±14.9) months.The incisions of the patients after the operation were all Grade A healing without infection, popliteal tendon injury, blood vessel injury, nerve injury and lower extremity venous thrombosis.The IKDC score increased from (49.7±3.6) points preoperatively to (88.5±4.4) points in the final follow-up ( P <0.05). The Lysholm score increased from (48.8±4.9) points preoperatively to (91.9±3.9) points at the final follow-up ( P <0.05). At 3, 6 months and 1 year after operation, according to Barrett's criteria, 54 cases were clinically healed, the healing rate was 94.7% (54/57)., Conclusion: This study preliminarily confirmed that arthroscopic suture technique can result in clinical stability through suture and fixation of the meniscus in the injured lateral popliteal tendon area. No adverse effects on knee joint function were found in the mid-term follow-up after the operation.

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds ( 1 - 11 ), including two γ -aromatic butenolides ( γ -AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ -butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.

Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.

China has a high dependence on soybean imports, yield increase at a faster rate is an urgent problem that need to be solved at present. The application of heterosis is one of the effective ways to significantly increase crop yield. In recent years, the development of an intelligent male sterility system based on recessive nuclear sterile genes has provided a potential solution for rapidly harnessing the heterosis in soybean. However, research on male sterility genes in soybean has been lagged behind. Based on transcriptome data of soybean floral organs in our research group, a soybean stamen-preferentially expressed gene GmFLA22a was identified. It encodes a fasciclin-like arabinogalactan protein with the FAS1 domain, and subcellular localization studies revealed that it may play roles in the endoplasmic reticulum. Take advantage of the gene editing technology, the Gmfla22a mutant was generated in this study. However, there was a significant reduction in the seed-setting rate in the mutant plants at the reproductive growth stage. The pollen viability and germination rate of Gmfla22a mutant plants showed no apparent abnormalities. Histological staining demonstrated that the release of pollen grains in the mutant plants was delayed and incomplete, which may due to the locule wall thickening in the anther development. This could be the reason of the reduced seed-setting rate in Gmfla22a mutants. In summary, our study has preliminarily revealed that GmFLA22a may be involved in regulating soybean male fertility. It provides crucial genetic materials for further uncovering its molecular function and gene resources and theoretical basis for the utilization of heterosis in soybean.

Catalyst design for the efficient CO 2 reduction reaction (CO 2 RR) remains a crucial challenge for the conversion of CO 2 to fuels. Natural Ni-Fe carbon monoxide dehydrogenase (NiFe-CODH) achieves reversible conversion of CO 2 and CO at nearly thermodynamic equilibrium potential, which provides a template for developing CO 2 RR catalysts. However, compared with the natural enzyme, most biomimetic synthetic Ni-Fe complexes exhibit negligible CO 2 RR catalytic activities, which emphasizes the significance of effective bimetallic cooperation for CO 2 activation. Enlightened by bimetallic synergy, we herein report a dinickel complex, Ni II Ni II (bphpp)(AcO) 2 (where NiNi(bphpp) is derived from H 2 bphpp = 2,9-bis(5- tert -butyl-2-hydroxy-3-pyridylphenyl)-1,10-phenanthroline) for electrocatalytic reduction of CO 2 to CO, which exhibits a remarkable reactivity approximately 5 times higher than that of the mononuclear Ni catalyst. Electrochemical and computational studies have revealed that the redox-active phenanthroline moiety effectively modulates the electron injection and transfer akin to the [Fe 3 S 4 ] cluster in NiFe-CODH, and the secondary Ni site facilitates the C-O bond activation and cleavage through electron mediation and Lewis acid characteristics. Our work underscores the significant role of bimetallic cooperation in CO 2 reduction catalysis and provides valuable guidance for the rational design of CO 2 RR catalysts., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In this study, we highlight the impact of catalyst geometry on the formation of O-O bonds in Cu 2 and Fe 2 catalysts. A series of Cu 2 complexes with diverse linkers are designed as electrocatalysts for water oxidation. Interestingly, the catalytic performance of these Cu 2 complexes is enhanced as their molecular skeletons become more rigid, which contrasts with the behavior observed in our previous investigation with Fe 2 analogs. Moreover, mechanistic studies reveal that the reactivity of the bridging O atom results in distinct pathways for O-O bond formation in Cu 2 and Fe 2 catalysts. In Cu 2 systems, the coupling takes place between a terminal Cu III -OH and a bridging μ-O⋅ radical. Whereas in Fe 2 systems, it involves the coupling of two terminal Fe-oxo entities. Furthermore, an in-depth structure-activity analysis uncovers the spatial geometric prerequisites for the coupling of the terminal OH with the bridging μ-O⋅ radical, ultimately leading to the O-O bond formation. Overall, this study emphasizes the critical role of precisely adjusting the spatial geometry of catalysts to align with the O-O bonding pathway., (© 2024 Wiley-VCH GmbH.)

We report herein the first nonheme CuFe oxygen reduction catalyst ([Cu II (bpbp)(μ-OAc) 2 Fe III ] 2+ , CuFe-OAc), which serves as a functional model of cytochrome c oxidase and can catalyze oxygen reduction to water with a turnover frequency of 2.4×10 3  s -1 and selectivity of 96.0 % in the presence of Et 3 NH + . This performance significantly outcompetes its homobimetallic analogues (2.7 s -1 of CuCu-OAc with %H 2 O 2 selectivity of 98.9 %, and inactive of FeFe-OAc) under the same conditions. Structure-activity relationship studies, in combination with density functional theory calculation, show that the CuFe center efficiently mediates O-O bond cleavage via a Cu II (μ-η 1  : η 2 -O 2 )Fe III peroxo intermediate in which the peroxo ligand possesses distinctive coordinating and electronic character. Our work sheds light on the nature of Cu/Fe heterobimetallic cooperation in oxygen reduction catalysis and demonstrates the potential of this synergistic effect in the design of nonheme oxygen reduction catalysts., (© 2023 Wiley-VCH GmbH.)

The selective reduction of carbon dioxide remains a significant challenge due to the complex multielectron/proton transfer process, which results in a high kinetic barrier and the production of diverse products. Inspired by the electrostatic and H-bonding interactions observed in the second sphere of the [NiFe]-CODH enzyme, researchers have extensively explored these interactions to regulate proton transfer, stabilize intermediates, and ultimately improve the performance of catalytic CO 2 reduction. In this work, a series of cobalt(II) tetraphenylporphyrins with varying numbers of redox-active nitro groups were synthesized and evaluated as CO 2 reduction electrocatalysts. Analyses of the redox properties of these complexes revealed a consistent relationship between the number of nitro groups and the corresponding accepted electron number of the ligand at -1.59 V vs. Fc +/0 . Among the catalysts tested, TNPPCo with four nitro groups exhibited the most efficient catalytic activity with a turnover frequency of 4.9 × 10 4 s -1 and a catalytic onset potential 820 mV more positive than that of the parent TPPCo. Furthermore, the turnover frequencies of the catalysts increased with a higher number of nitro groups. These results demonstrate the promising design strategy of incorporating multielectron redox-active ligands into CO 2 reduction catalysts to enhance catalytic performance., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The shoulder joint is the most flexible joint in the body with the largest range of motion, and the movement pattern is more complex. Accurate capture of three-dimensional motion data of the shoulder joint is crucial for biomechanical evaluation. Optical motion capture systems offer a non-invasive and radiation-free method to capture shoulder joint motion data during complex movements, enabling further biomechanical analysis of the shoulder joint. This review provides a comprehensive overview of optical motion capture technology in the context of shoulder joint movement, including measurement principles, data processing methods to reduce artifacts from skin and soft tissues, factors influencing measurement results, and applications in shoulder joint disorders.

We reported herein the development of heterobimetallic NiFe molecular platform to understand NiFe synergistic effect in water oxidation catalysis. Compared to homonuclear bimetallic compounds (NiNi and FeFe), NiFe complex possesses more remarkable catalytic water oxidation performance. Mechanistic studies suggest that this remarkable difference is attributed to the fact that NiFe synergy can effectively promote O-O bond formation. The generated Ni III (μ-O)Fe IV =O is the key intermediate and O-O bond was formed via intramolecular oxyl-oxo coupling between bridged O radical and terminal Fe IV =O moiety., (© 2023 Wiley-VCH GmbH.)

The parasubthalamic nucleus (PSTN) is considered to be involved in motivation, feeding and hunting, all of which are highly depending on wakefulness. However, the roles and underlying neural circuits of the PSTN in wakefulness remain unclear. Neurons expressing calretinin (CR) account for the majority of PSTN neurons. In this study in male mice, fiber photometry recordings showed that the activity of PSTN CR neurons increased at the transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior. Chemogenetic and optogenetic experiments demonstrated that PSTN CR neurons were necessary for initiating and/or maintaining arousal associated with exploration. Photoactivation of projections of PSTN CR neurons revealed that they regulated exploration-related wakefulness by innervating the ventral tegmental area. Collectively, our findings indicate that PSTN CR circuitry is essential for the induction and maintenance of the awake state associated with exploration., (© 2023. The Author(s).)

Superior labrum anterior posterior (SLAP) injury is a major challenge for orthopedic surgeons, due to the poor healing ability of the injured labrum. Although arthroscopic surgery is the gold standard for the treatment of SLAP injury, there are still disputes about the adaptation of different surgical techniques, the choice of anchors during operation, knotted or knotless anchors, and fixation methods. The authors believe that arthroscopic repair of SLAP lesions is effective for young patients with intact glenoid labrum(<35 years old) or with extensive activity, where single and knotless anchor is preferred. For the older patients(≥35 years old) with degeneration and wear of glenoid labrum, biceps tenodesis is more preferable, and interference screw fixation technique is recommended. As for patients with failed SLAP repair, biceps tenodesis can achieve a high success rate as a revision surgery. By review of the relevant literature in recent years, this paper summarizes the adaptation of different surgical methods of arthroscopic treatment of SLAP injury, intraoperative anchoring techniques, fixation methods and other improved surgical techniques.

Introduction: Symptoms of gastric motility disorders are common clinical manifestations of functional gastrointestinal disorders (FGIDs), and are triggered and exacerbated by stress, but the neural pathways underpinning them remain unclear., Methods: We set-up a mouse model by gastric dilation (GD) in which the gastric dynamics were assessed by installing strain gauges on the surface of the stomach. The neural pathway associated with gastric motility disorders was investigated by behavioral tests, electrophysiology, neural circuit tracing, and optogenetics and chemogenetics involving projections of the corticotropin-releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus (PVN) to acetylcholine (ChAT) neurons in the dorsal motor nucleus of the vagus (DMV)., Results: We found that GD induced gastric motility disorders were accompanied by activation of PVN CRH neurons, which could be alleviated by strategies that inhibits the activity of PVN CRH neurons. In addition, we identified a neural pathway in which PVN CRH neurons project into DMV ChAT neurons, modulated activity of the PVN CRH →DMV ChAT pathway to alleviate gastric motility disorders induced by GD., Discussion: These findings indicate that the PVN CRH →DMV ChAT pathway may mediate at least some aspects of GD related gastric motility, and provide new insights into the mechanisms by which somatic stimulation modulates the physiological functions of internal organs and systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Chen, Wang, Cai, Wang, Wang, Peng, Zhang, Huang and Shen.)

Background/aims: Psychological and physiological stress can cause gastrointestinal motility disorders. Acupuncture has a benign regulatory effect on gastrointestinal motility. However, the mechanisms underlying these processes remain unclear. Methods: Herein, we established a gastric motility disorder (GMD) model in the context of restraint stress (RS) and irregular feeding. The activity of emotional center-central amygdala (CeA) GABAergic neurons and gastrointestinal center-dorsal vagal complex (DVC) neurons were recorded by electrophysiology. Virus tracing and patch clamp analysis of the anatomical and functional connection between the CeA GABA → dorsal vagal complex pathways were performed. Optogenetics inhibiting or activating CeA GABA neurons or the CeA GABA → dorsal vagal complex pathway were used to detect changes in gastric function. Results: We found that restraint stress induced delayed gastric emptying and decreased gastric motility and food intake. Simultaneously, restraint stress activated CeA GABAergic neurons, inhibiting dorsal vagal complex neurons, with electroacupuncture (EA) reversing this phenomenon. In addition, we identified an inhibitory pathway in which CeA GABAergic neurons project into the dorsal vagal complex. Furthermore, the use of optogenetic approaches inhibited CeA GABA neurons and the CeA GABA → dorsal vagal complex pathway in gastric motility disorder mice, which enhanced gastric movement and gastric emptying, whereas activation of the CeA GABA and CeA GABA → dorsal vagal complex pathway mimicked the symptoms of weakened gastric movement and delayed gastric emptying in naïve mice. Conclusion: Our findings indicate that the CeA GABA → dorsal vagal complex pathway may be involved in regulating gastric dysmotility under restraint stress conditions, and partially reveals the mechanism of electroacupuncture., Competing Interests: HW was employed by Hefei Industrial Pharmaceutical Institute Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liu, Wang, Chen, Cai, Zhang, Wang, He, Zhang and Shen.)

Planktonic and epiphytic bacterial communities play an important role in wetland nitrogen pollutant removal and water purification, yet their community dynamics are far from understood compared with those of the wetland soil bacterial community. Taking the planktonic bacterial community in the Yuguqiao constructed wetland and the epiphytic bacterial community on the leaf surface of the common submerged plant Vallisneria natans as the research objects, the composition, structure, and functional diversity of planktonic and epiphytic bacterial communities were analyzed using high-throughput sequencing. The results showed that the compositions of the planktonic and epiphytic bacterial communities were significantly different, with more heterotrophic and denitrifying bacteria present in the epiphytic bacterial community than in the planktonic bacterial community. The α diversity of the planktonic bacterial community was significantly different among the three sampling sites but not in the epiphytic bacterial community. In general, the OTU index and Shannon index of the epiphytic bacterial community were significantly higher than those of the planktonic bacterial community, and they had obvious spatial heterogeneity. RDA analysis showed that DO, IC, TP, NH + 4 , and TOC had important effects on the structural changes of both planktonic and epiphytic bacterial communities but had a greater impact on planktonic bacterial communities. Co-occurrence network analysis showed that the epiphytic bacterial community had more niche differentiation, a more stable network, and stronger resistance to external disturbance. The results of FAPROTAX functional prediction analysis showed that the nitrogen cycling, especially denitrification of the epiphytic bacterial community, was significantly greater than that of the planktonic bacterial community. The results of this study revealed the driving mechanism for maintaining the diversity of planktonic and epiphytic bacterial communities, which can provide a scientific basis for excavating and utilizing planktonic and epiphytic bacterial community resources in the construction of constructed wetlands to improve the efficiency of water purification.

Nitrogen is an important factor affecting crop yield, but excessive use of chemical nitrogen fertilizer has caused decline in nitrogen utilization and soil and water pollution. Reducing the utilization of chemical nitrogen fertilizers by biological nitrogen fixation (BNF) is feasible for green production of crops. However, there are few reports on how to have more ammonium produced by nitrogen-fixing bacteria (NFB) flow outside the cell. In the present study, the amtB gene encoding an ammonium transporter (AmtB) in the genome of NFB strain Kosakonia radicincitans GXGL-4A was deleted and the △amtB mutant was characterized. The results showed that deletion of the amtB gene had no influence on the growth of bacterial cells. The extracellular ammonium nitrogen (NH 4 + ) content of the △amtB mutant under nitrogen-free culture conditions was significantly higher than that of the wild-type strain GXGL-4A (WT-GXGL-4A), suggesting disruption of NH 4 + transport. Meanwhile, the plant growth-promoting effect in cucumber seedlings was visualized after fertilization using cells of the △amtB mutant. NFB fertilization continuously increased the cucumber rhizosphere soil pH. The nitrate nitrogen (NO 3 - ) content in soil in the △amtB treatment group was significantly higher than that in the WT-GXGL-4A treatment group in the short term but there was no difference in soil NH 4 + contents between groups. Soil enzymatic activities varied during a 45-day assessment period, indicating that △amtB fertilization influenced soil nitrogen cycling in the cucumber rhizosphere. The results will provide a solid foundation for developing the NFB GXGL-4A into an efficient biofertilizer agent., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The surgical treatment of massive rotator cuff tears is a clinical challenge for orthopaedic surgeons. Moreover, tendon retraction, adhesions and fatty infiltration after rotator cuff tear will further increase the difficulty of surgical repair. Therefore, it has become a hotspot and difficulty to repair massive rotator cuff tears with a better way in current research. In recent years, with the continuous development of arthroscopic techniques, shoulder arthroscopic surgery has become the gold standard for the treatment of massive rotator cuff tears, but the adaptations, effects and combined application of different surgical methods are still controversial. The author believes that arthroscopic debridement of shoulder joint and acromioplasty or tuberoplasty could relieve shoulder pain in the short-term for elderly patients with lower functional requirements;long biceps tenotomy or tenodesis is effective for patients with biceps long head tendon injury; complete repair is still the first line treatment for massive rotator cuff tears, but partial repair is possible for massive rotator cuff tears that could not be completely repaired;patch augmentation technology could bring good results for young patients with high functional requirements;for patients with limited internal and external rotation of the shoulder joint and high functional requirements, tendon transfers surgery is recommended;superior capsular reconstruction is more advantageous for young patients with no obvious glenohumeral arthritis, better deltoid muscle strength and higher functional requirements. In addition, subacromial spacer implantation has become a current research hotspot due to its advantages of small trauma, low cost and relative safety, and its long-term effect still needs to be further confirmed.

Background and Aims: Natural killer (NK) cells play an important role in biliary atresia (BA) pathogenesis; human poliovirus receptor (PVR) is an important NK-cell modulator. Here, we explored the role of PVR in BA pathogenesis., Methods: Poliovirus receptor expression and NK cell-associated genes were detected in human BA samples and a rotavirus-induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK-cell-mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high-mobility group box 1 (HMGB1), and interleukin-1beta (IL-1beta) levels were measured in a cohort of 50 patients using ELISA., Results: Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus-induced BA. Activation of the TLR3-IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell-mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL-1beta levels., Conclusions: Poliovirus receptor contributes to BA pathogenesis by regulating NK cell-mediated bile duct injury; PVR has the value as a biomarker of BA., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Transition metal-nitrogen-carbon (TM-N-C) catalysts have been intensely investigated to tackle the sluggish oxygen reduction reactions (ORRs), but insufficient accessibility of the active sites limits their performance. Here, by using solid ZIF-L nanorods as self-sacrifice templates, a ZIF-phase-transition strategy is developed to fabricate ZIF-8 hollow nanorods with open cavities, which can be subsequently converted to atomically dispersed Fe-N-C hollow nanorods (denoted as Fe 1 -N-C HNRs) through rational carbonization and following fixation of iron atoms. The microstructure observation and X-ray absorption fine structure analysis confirm abundant Fe-N 4 active sites are evenly distributed in the carbon skeleton. Thanks to the highly accessible Fe-N 4 active sites provided by the highly porous and open carbon hollow architecture, the Fe 1 -N-C HNRs exhibit superior ORR activity and stability in alkaline and acidic electrolytes with very positive half-wave potentials of 0.91 and 0.8 V versus RHE, respectively, both of which surpass those of commercial Pt/C. Remarkably, the dynamic current density (J K ) of Fe 1 -N-C HNRs at 0.85 V versus RHE in alkaline media delivers a record value of 148 mA cm -2 , 21 times higher than that of Pt/C. The assembled Zn-air battery using Fe 1 -N-C HNRs as cathode catalyst exhibits a high peak power density of 208 mW cm -2 ., (© 2022 Wiley-VCH GmbH.)

Objective: To investigate the method and clinical effects of the treatment of recurrent shoulder dislocation with severe glenoid injury by arthroscopic subscapularis augmentation., Methods: From March 2019 to August 2020, 16 patients with recurrent dislocation of shoulder with severe glenoid injury underwent arthroscopic subscapularis augmentation, including 10 males and 6 females, aged from 18 to 50 years old with an average of (29.06±10.54) years old, 4 cases of left shoulder and 12 cases of right shoulder.Visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES) score and Rowe score were used to evaluate shoulder function and stability before and after operation., Results: All the 16 patients were followed up from 12 to 29 months, with an average of (18.75±7.26) months. VAS score decreased from 5.25±1.13 before operation to 1.37±0.65 at the final follow-up;ASES score increased from 59.44±9.93 before surgery to 90.88±4.00 at the final follow-up; Rowe score of shoulder increased from 51.56±8.89 before surgery to 92.19±7.06 at the final follow-up, and the differences were statistically significant ( P <0.05). No dislocation was observed during follow-up. No clinical complications such as incision infection, vascular and nerve injury occurred in all patients after operation., Conclusion: Arthroscopic subscapularis augmentation in the treatment of recurrent dislocation of shoulder with severe glenoid injury is satisfactory. It is an effective treatment method of recurrent dislocation of shoulder joint with severe glenoid injury, and external rotation function in patients with almost unaffected.

Kosakonia radicincitans GXGL-4A, a gram-negative nitrogen-fixing (NF) bacterial strain is coated with a thick capsulatus on the surface of cell wall, which becomes a physical barrier for exogenous DNA to enter the cell, so the operation of genetic transformation is difficult. In this study, an optimized Tn5 transposon mutagenesis system was established by using a high osmotic HO-1 medium combined with the electroporation transformation. Eventually, a mutant library containing a total of 1633 Tn5 insertional mutants were established. Of these mutants, the mutants M81 and M107 were found to have an enhanced capability to synthesize siderophore through the CAS agar plate assay and the spectrophotometric determination. The bacterial cells of two mutants were applied in cucumber growth-promoting experiment. Cucumber seedlings treated with M81 and M107 cells had a significant increase in biomass including seedling height, seedling fresh weight, root fresh weight, and root length. The whole genome sequencing of the mutants M81 and M107 showed that the integration sites of Tn5 transposon element were located in MmyB-like helix-turn-helix transcription regulator (locus tag: A3780&#95;19720, trX) and aminomethyltransferase-encoding genes (locus tag: A3780&#95;01680, amt) in the genome of GXGL-4A, respectively. The ability of siderophore synthesis of the target mutants was improved by Tn5 insertion mutagenesis, and the mutants obtained showed a good plant growth-promoting effect when applied to the cucumber seedlings. The results suggest that the identified functional genes regulates the biosynthesis of siderophore in azotobacter GXGL-4A, and the specific mechanism needs to be further investigated., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Molecular catalysis of water oxidation has been intensively investigated, but its mechanism is still not yet fully understood. This study aims at capturing and identifying key short-lived intermediates directly during the water oxidation catalyzed by a cobalt-tetraamido macrocyclic ligand complex using a newly developed an in situ electrochemical mass spectrometry (EC-MS) method. Two key ligand-centered-oxidation intermediates, [(L 2- )Co III OH] and [(L 2- )Co III OOH], were directly observed for the first time, and further confirmed by 18 O-labeling and collision-induced dissociation studies. These experimental results further confirmed the rationality of the water nucleophilic attack mechanism for the single-site water oxidation catalysis. This work also demonstrated that such an in situ EC-MS method is a promising analytical tool for redox catalytic processes, not only limited to water oxidation.

Three new species of Himalaphantes Tanasevitch, 1992 from Yunnan province, China, are described: H.arcuatus sp. nov. (♀), H.lingulatus sp. nov. (♂♀), and H.uncatus sp. nov. (♂♀). The diagnosis of the genus is clarified, and extended detailed descriptions, photographs of somatic features and copulatory organs, and a distribution map are provided., (Meng-ting Zhang, Ping Liu, Muhammad Irfan, Xian-jin Peng.)

Objectives: We researched the effect and mechanism of acupuncture treatment for visceral pain in rats with diarrhea-predominant irritable bowel syndrome (IBS-D)., Methods: We set up a rat model of IBS-D with chemical and chronic- and acute-pressure stimulations. Then, the IBS-D rats were treated with acupuncture or 5-BDBD, and the therapeutic efficacy of acupuncture in IBS-D rats was assessed by means of the Bristol scale, diarrhea index, abdominal withdrawal reflex (AWR) score, mast cell count and histologic staining., Results: Acupuncture significantly decreased clinical symptoms in IBS-D rats after a 14 day-treatment. Furthermore, significant down-regulation of P2X4, OX42, BDNF (brain-derived neurotrophic factor) and IRF-5 (interferon regulatory factor 5) expressions were observed in the IBS-D rats, along with the decreased inflammatory factors [interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6)], chemokines [monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), and C-X-C motif chemokine ligand 1 (CXCL1)], and neurotransmitters [substance P (SP), 5-hydroxytryptamine (5-HT), and calcitonin gene-related peptide (CGRP)]. 5-BDBD treatment had a similar effect on IBS-D rats., Conclusions: Acupuncture can effectively alleviate abdominal pain by decreasing visceral hypersensitivity and controlling the expression of P2X4 and spinal microglial inflammation in IBS rats., Competing Interests: None., (AJTR Copyright © 2022.)

The incidence of re-tearing after rotator cuff repair is very high. The main reason is that the tendon-osseous junction after the operation is scar healed. In response to this problem, research in recent years has focused on the application of grafts, including cell transplantation, periosteum transplantation, cartilage transplantation, and biosynthetic transplantation. Cell transplantation is mainly a variety of stem cells from different sources. The current research has confirmed that it can achieve better results. The combined application of exosomes and stem cells may be the future development direction. Periosteum transplantation is a promising intervention method, but few clinical applications at present, and there are problems such as limited sources of materials and secondary trauma from the materials. Tissue engineered periostium and artificial bionic periostium may be alternatives to periosteal;cartilage transplantation can promote the regeneration of cartilage at the tendon-osseous junction and facilitate tendon-bone healing. However, there are also limited materials and secondary damage. There is no better solution to this problem. The slow degradation of inorganic composites and the poor effect of single use limit its application; biological derivatives have immunogenicity, poor biomechanics and other issues, there is currently no proper solution; organic synthetic grafts pay more attention to simulating the structure of the physiological tendon-osseointegration zone, and show good results in tendon-bone healing, and have good application prospects. In addition, most of the above-mentioned application research of different grafts stays at the cellular and animal level, and more research is needed in clinical application. This article briefly reviews the application status, advantages, disadvantages and development trends of the above-mentioned different grafts, in order to provide certain guidance for the clinical treatment of rotator cuff tears.

The proton-coupled electron transfer (PCET) reaction has drawn extensive attention for its widespread occurrence in chemistry, biology, and materials science. The mechanistic studies via model systems such as tyrosine and phenol oxidation have gradually deepened the understanding of PCET reactions, which was widely accepted and applied to bond activation and transformation. However, direct PCET activation of nonpolar bonds such as the C-H bond, O 2 , and N 2 has yet to be explored. Herein, we report that the interaction between electron donor and proton donor could overcome the barrier of direct O 2 activation via a concerted electron-proton transfer mechanism. This work provides a new strategy for developing direct PCET activation of nonpolar bonds.

Objective: To compare difference in clnical efficacy between arthroscopic double posterior internal approach and incisional surgery for acute simple posterior cruciate ligament tibial avulsion fractures., Methods: Totally 52 patients with acute simple posterior cruciate ligament tibial avulsion fractures treated from June 2016 to June 2020 were retrospectively analyzed and divided into two groups according to different surgical protocols, 27 patients in arthroscopic group were treated with arthroscopic double posterior internal approach, including 16 males and 11 females, aged from 19 to 52 years old, with an average age of (34.9±9.2) years old;25 patients in open reduction group were treated with posterior medial knee incision, including 14 males and 11 females, aged from 18 to 54 years old , with an average age of(33.7±8.4) years old. Operation time, incision length, intraoperative bleeding, hospitalization days, hospitalization cost, fracture healing, complications, postoperative Lysholm score and IKDC score at 12 months were observed and compared between two groups., Results: All patients in both groups were completed opertaion successfully without vascular or nerve injury, and 52 patients were followed up from 6 to 24 months with an average of (15.0±1.7) months. Operation time and hospitalization cost in arthroscopic group were significantly greater than those in open reduction group( P <0.05);intraoperative bleeding, incision length, and hospitalization days in arthroscopic group were less than those in open reduction group( P <0.05);preoperative Lysholm score in arthroscopic group and open reduction group were 49.1±2.3 and 48.9±1.1 respectively, and improved to 95.9±1.7 and 86.4±1.2 at 12 months after operation respectively( P <0.05);preoperative IKDC scores in arthroscopic group and open reduction group were 47.6±4.1 and 48.1±3.9 respectively, and improved to 96.9±1.5 and 87.1±1.4 at 12 months after operation( P <0.05)., Conclusion: Arthroscopic double posterior internal approach for acute simple posterior cruciate ligament tibial stop avulsion fracture has satisfactory early results and better efficacy than traditional open surgery, which has advantages of less trauma, faster recovery and easier operation.

Advanced glycation end products(AGEs) can lead to many diseases such as diabetes and its complications. In this study, an in vitro non-enzymatic glycosylation reaction model-bovine serum albumin/methylglyoxal(BSA/MGO) reaction system was constructed and incubated with Cortex Moutan extract. High performance liquid chromatography(HPLC) and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) were used to detect and identify the active components that inhibited the formation of AGEs in the co-incubation solution of Cortex Moutan extract and MGO, and differential components such as salvianan, paeoniside, benzoylpaeoniflorin, mudanpioside J, galloyloxypaeoniflorin, benzoyloxy-paeoniflorin, 5-hydroxy-3 s-hydroxymethyl-6-methyl-2,3-dihydro benzofuran, and galloylpaeoniflorin were screened out, which were inferred to be the potential active components of Cortex Moutan extract to capture MGO. In addition, BSA-glucose reaction system was performed to investigate the influence of different concentrations of Cortex Moutan extract(decoction concentrations: 40, 80, 120, 160, and 200 mg·mL~(-1)) on inhibiting the production of AGEs in vitro. The inhibitory effects of Cortex Moutan extract and the differential components galloylpaeoniflorin and benzoyl paeoniflorin on the production of AGEs in human umbilical vein endothelial cells(HUVECs) induced by high glucose was further evaluated. Cell apoptosis was observed by acridine orange and ethidium bromide(AO/EB) double fluorescence staining. The results showed that Cortex Moutan Cortex extract and its differential components had certain inhibitory effects on the formation of AGEs, and could reduce cell apoptosis. This study provided reference for the treatment of diabetic vascular complications by Cortex Moutan inhibiting the toxic AGEs.

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, β-1,3-d-Galp and β-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To investigate the early efficacy of arthroscopic autologous osteochondral grafting in the treatment of recurrent anterior shoulder dislocation., Methods: From January 2019 to January 2021, 17 patients with recurrent anterior dislocation of shoulder who underwent arthroscopic autologous osteochondral grafting were selected, including 12 males and 5 females, ranging in age from 17 to 55 years old, with a mean of (32.88±12.33) years old. Rowes rating system for Bankart repair(Rowe), Oxford Shoulder Instability Score (OSIS) and Simple Shoulder Test (SST) were compared before operation, 6 months after operation and at the latest follow-up. OSIS and SST used to evaluate shoulder function were recorded before surgery and at the latest follow-up. The shoulder mobility and intraoperative and postoperative complications were also recorded., Results: All 17 patients were followed up, and the duration ranged from 7 to 25 months, with a mean of (18.4±5.4) months. During the follow-up period, there was no re-dislocation, no vascular or nerve injury. Rowe score increased from 26.2±6.0 before operation to 74.4±4.0 and 82.4±3.1 after 6 months and the latest follow-up. There was significant difference in Rowe score between different time points after operation and before operation ( P <0.05). The OSIS increased from 37.0±3.6 before operation to 47.4±2.6 and 52.7±2.6 after 6 months and the latest follow-up. There was significant difference in OSIS between different time points after operation and before operation ( P <0.05). The SST score increased from 6.8±0.7 before operation to 9.8±0.8, 11.6±2.6 after 6 months and the latest follow-up. There was significant difference in SST score between different time points after operation and before operation ( P <0.05). At the latest follow-up, the lateral external rotation and abduction external rotation activities of the patient were significantly improved compared with those before operation., Conclusion: This study provides preliminary evidence that arthroscopic autologous osteochondral grafting can achieve satisfactory early clinical outcomes and stability in patients with recurrent anterior shoulder dislocation with glenoid fracture and defect less than <20%, which is a reliable and effective procedure.

In this work, a laser-induced fluorescence (LIF) detection system built in a modular assembling mode was developed based on commercial LEGO blocks and 3D printed blocks. We designed and fabricated a variety of 3D printed building blocks fixed with optical components, including laser light source, filters, lens, dichroic mirror, photodiode detector, and control circuits. Utilizing the relatively high positioning precision of the plug-in blocks, a modular construction strategy was adopted using the flexible plug-in combination of the blocks to build a highly sensitive laser-induced fluorescence detection system, LIFGO. The LIFGO system has a simple structure which could be constructed by inexperienced users within 3 h. We optimized the structure and tested the performance of the LIFGO system, and its detection limits for sodium fluorescein solution in 100 μm i.d. and 250 μm i.d. capillaries were 7 nM and 0.9 nM, respectively. Based on the LIFGO system, we also built a simple capillary electrophoresis (CE) system and applied it to the analysis of DNA fragments to demonstrate its application possibility in biochemical analysis. The separation of 7 fragments in DL500 DNA markers were completed in 600 s. Because of the features of low cost (less than $100) and easy-to-build construction, we introduced the LIFGO system to the experimental teaching of instrumental analysis for undergraduate students. The modular construction form of the LIF detection system greatly reduces the threshold of instrument construction, which is conducive to the popularization of the LIF detection technique in routine laboratories as well as the reform of experimental teaching mode., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of adenovirus-mediated shRNA down-regulating phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on vinculin, filamin A, and cortactin in activated hepatic stellate cells (HSCs). Methods: Activated rats hepatic stellate cell line (HSC-T6) was cultured in vitro. Recombinant adenovirus Ad-shRNA/PTEN carrying PTEN targeted RNA interference sequence [short hairpin RNA (shRNA)] and empty control virus Ad-GFP were transfected into HSCs. The PTEN mRNA and protein expression of HSCs in each group were detected by real-time fluorescence quantitative PCR and Western blot. The expressional change of vinculin, filamin A and cortactin in HSCs of each group were detected by confocal laser scanning immunofluorescence microscope. Image-pro plus 6.0 software was used for image analysis and processing. The integrated optical density (IOD) of the fluorescence protein expression was measured. The experiment was divided into three groups: control group (DMEM instead of adenovirus solution in the adenovirus transfection step), Ad-GFP group (transfected with empty virus Ad-GFP only expressing green fluorescent protein), and Ad-shRNA/PTEN group (recombinant adenovirus Ad-shRNA/PTEN carrying shRNA targeting PTEN and expressing green fluorescent protein). One-way analysis of variance was used for comparison of mean value among the three groups, and LSD-test was used for comparison between the groups. Results: shRNA targeted PTEN was successfully transfected and the expression of PTEN mRNA and protein in HSC ( P < 0.05) was significantly down-regulated. HSCs vinculin was mainly expressed in the cytoplasm. HSCs vinculin fluorescence IOD in the Ad-shRNA/PTEN group (19 758.83 ± 1 520.60) was higher than control (7 737.16 ± 279.93) and Ad-GFP group (7 725.50 ± 373.03) ( P < 0.05), but there was no statistically significant difference between control group and Ad-GFP group ( P > 0.05). There was no statistically significant difference in the fluorescence IOD of Filamin A among the three groups ( P > 0.05), but the subcellular distribution of Filamin A among the three groups were changed. Filamin A in the Ad-shrNA /PTEN HSC group was mainly distributed in the cytoplasm. Filamin A HSC was mainly located in the nucleus.The filamin A HSC in the control group and Ad-GFP group was mainly located in the nucleus. The nucleocytoplasmic ratio of Filamin A in the AD-shrNA /PTEN group (0.60 ± 0.15) was significantly lower than control group (1.20 ± 0.15) and Ad-GFP group (1.08 ± 0.23), P < 0.05. but there was no statistically significant difference in filamin A nucleocytoplasmic ratio of HSC between the control group and the Ad-GFP group ( P > 0.05). Cortactin HSCs in the three groups was mainly distributed in the cytoplasm. The cortactin fluorescence IOD of HSCs in the Ad-shRNA/PTEN group was significantly higher than control group (22 959.94 ± 1 710.42) and the Ad-GFP group (22 547.11 ± 1 588.72 ) ( P < 0.05), while there was no statistically significant difference in the IOD of cortactin fluorescence in HSCs between the control group and the Ad-GFP group ( P > 0.05). Conclusion: The down-regulation of PTEN expression raises the expression of microfilament-binding protein vinculin and cortactin, and changes the subcellular distribution of another microfilament binding protein filamin A, that is, translocation from nucleus to the cytoplasm in activated HSC in vitro.

Oxidation reactions are fundamental transformations in organic synthesis and chemical industry. With oxygen or air as terminal oxidant, aerobic oxidation catalysis provides the most sustainable and economic oxidation processes. Most aerobic oxidation catalysis employs redox metal as its active center. While nature provides non-redox metal strategy as in pyrroloquinoline quinone (PQQ)-dependent methanol dehydrogenases (MDH), such an effective chemical version is unknown. Inspired by the recently discovered rare earth metal-dependent enzyme Ln-MDH, here we show that an open-shell semi-quinone anionic radical species in complexing with lanthanum could serve as a very efficient aerobic oxidation catalyst under ambient conditions. In this catalyst, the lanthanum(III) ion serves only as a Lewis acid promoter and the redox process occurs exclusively on the semiquinone ligand. The catalysis is initiated by 1e - -reduction of lanthanum-activated ortho-quinone to a semiquinone-lanthanum complex La(SQ -. ) 2 , which undergoes a coupled O-H/C-H (PCHT: proton coupled hydride transfer) dehydrogenation for aerobic oxidation of alcohols with up to 330 h -1 TOF., (© 2022. The Author(s).)

Solar-powered water splitting is a dream reaction for constructing an artificial photosynthetic system for producing solar fuels. Natural photosystem II is a prototype template for research on artificial solar energy conversion by oxidizing water into molecular oxygen and supplying four electrons for fuel production. Although a range of synthetic molecular water oxidation catalysts have been developed, the understanding of O-O bond formation in this multielectron and multiproton catalytic process is limited, and thus water oxidation is still a big challenge. Herein, we report a trinuclear copper cluster that displays outstanding reactivity toward catalytic water oxidation inspired by multicopper oxidases (MCOs), which provides efficient catalytic four-electron reduction of O 2 to water. This synthetic mimic exhibits a turnover frequency of 20000 s -1 in sodium bicarbonate solution, which is about 150 and 15 times higher than that of the mononuclear Cu catalyst (F-N 2 O 2 Cu, 131.6 s -1 ) and binuclear Cu 2 complex (HappCu 2 , 1375 s -1 ), respectively. This work shows that the cooperation between multiple metals is an effective strategy to regulate the formation of O-O bond in water oxidation catalysis.

Recurrent anterior dislocation of shoulder with bone defect is one of the common diseases of shoulder joint. How to effectively repair glenoid bone defect and reduce recurrence rate of shoulder dislocation is a problem that clinicians focus on. Bone grafting could stimulate bone, promote bone regeneration and bone remodeling, and restore the normal anatomical structure of glenoid. Among them, Bristow-Latarjet procedure is a classic operation for recurrent shoulder dislocation. Latarjet procedure could repair larger glenoid bone defects, but with higher surgical skills for surgeons;autogenous iliac grafting is the first choice for revision once Latarjet procedure failed;osteochondral grafting (autogenous and allogenous) has certain advantages in reconstructing original articular surface and preventing joint degeneration, but autologous osteochondral grafting may cause secondary injury, while immune rejection is difficult to avoid for allogenous osteochondral grafting. With the improvement of composite materials, and the mechanism of bone regeneration and remodeling, as well as the advantages and disadvantages of bone grafting, tissue engineering technology may become an effective method for the treatment of glenoid bone defect in the future.

Morphine and other opiates are highly effective for treating moderate to severe pain. However, morphine-induced hyperalgesia and analgesic tolerance prevent durable efficacy in patients. Here, we investigated the underlying molecular mechanisms of this phenomenon. We found that repeated subcutaneous injections of morphine in mice increased the abundance of the cytokine interleukin-33 (IL-33) primarily in oligodendrocytes and astrocytes and that of its receptor ST2 mainly in astrocytes. Pharmacological inhibition or knockdown of IL-33 or ST2 in the spinal cord attenuated morphine-induced hyperalgesia and analgesic tolerance in mice, as did global knockout of either Il33 or St2 , which also reduced morphine-enhanced astroglial activation and excitatory synaptic transmission. Furthermore, a pathway mediated by tumor necrosis factor receptor–associated factor 6 (TRAF6) and the kinase JNK in astrocytes was required for IL-33–mediated hyperalgesia and tolerance through promoting the production of the chemokine CXCL12 in the spinal cord. The findings suggest that targeting IL-33–ST2 signaling could enable opioids to produce sustained analgesic effects in chronic pain management.

In this study, a facile and environmentally friendly synthesis process was proposed without regular chemical additives. We successfully synthesized spherical gold nanoparticles (AuNPs) coated with glycyrrhizin (GL) by using GL as both a reductant and a stabilizer to reduce chloroauric acid. The obtained NPs were approximately 35 nm in size. The formation of these GL-AuNPs was verified by the presence of a surface plasmon resonance band at 526 nm. We also experimentally determined that in terms of chemical structure, GL can be used as a reducing agent to obtain colloidal gold. The d-glucuronic acid structure, rather than glycyrrhetinic acid (GA), plays an important reducing role in colloidal gold production. From this, we hypothesized that other compounds with sugar structures in Glycyrrhiza may also have the ability to reduce chloroauric acid. To mitigate the high cost and low efficiency of current GL detection methods, we applied AuNPs to the immunochromatographic system. Then, a colloidal gold immunochromatographic test strip based on the indirect competition method was developed for the rapid detection of GL, and the detection limit of this strip was 25 ng mL -1 . The cross-test showed that the strip has high specificity. The test results are consistent with the data obtained by high-performance liquid chromatography (HPLC) with a coincidence rate of up to 100%. The rapid test strip is simple, fast, highly efficient and inexpensive, making it suitable for large-scale, rapid glycyrrhizin content determination., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p<0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.

Background: Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used to improve cognitive impairment. However, the underlying neuroprotective mechanism of HPTQ treated for diabetic cognitive dysfunction (DCD) remains unclear. The purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking., Methods: To investigate the neuroprotective effect of HPTQ in DCD, the Morris water maze (MWM), novel object recognition (NOR) test was used to detect the learning and memory changes of mice; hematoxylin-eosin (HE) staining was used to investigate the damage of hippocampal neurons; the western blot (WB) was used to examine the level of brain-derived neurotrophic factor (BDNF) of hippocampus. To investigate the neuroprotective mechanism of HPTQ in DCD, molecular docking was used to predict the possible target proteins of different active components in HPTQ and then the WB was used to verify the expression of key target proteins in the hippocampus of mice., Results: HPTQ improved the learning and memory ability, hippocampal neuron damage, and the level of BDNF in the hippocampus of the DCD model treated with HFD/STZ for 12 weeks. Besides, the results of molecular docking showed that the main chemical components of HPTQ could be well combined with the targets of Bcl-2-associated X (Bax) and B-cell lymphoma2 (Bcl-2) and caspase-3. The levels of Bax/Bcl-2 protein ratio and caspase-3 increased in the DCD model while the HPTQ inhibited it. In addition, HPTQ restored DCD-induced decline of p-CREB, BDNF, TrkB, and p-Akt in the hippocampus., Conclusions: These data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway., Competing Interests: The authors report no declarations of interest., (Copyright © 2021 Shu Ye et al.)

We explored the effects of disturbance densities on the spatial pattern and the association of tree species in the coniferous broadleaved mixed forest in Pangquangou Nature Reserve of Guandi Mountain. Using three factors including canopy density, stand density and number of stumps, we classified the disturbance intensities of different forest stands into three levels, non-disturbance, moderate disturbance, and severe disturbance. The spatial distribution pattern and the association of different tree species were analyzed by spatial point pattern K2 function. The results showed that the diameter distribution of trees in undisturbed plots was inverted 'J' type, while that of moderate disturbance and serious disturbance plots was under bimodal curve distribution. The stand distribution pattern showed a small-scale aggregated distribution under undisturbed and moderately distur-bance, and a random distribution under heavy disturbance. At the small scale, the coniferous and broadleaved species showed no correlation in undisturbed stands, were positively correlated in moderately disturbed stands, and negatively correlated in seriously disturbed stands. At large scale, they were no correlated in both moderately and seriously disturbed stands. The results suggested that abundance of trees with small diameter in the forests was negatively with disturbance intensity, which led to the lower degree of intraspecific aggregation at small scale. Meanwhile, appropriate levels of disturbance would benefit the collaborative use of environmental resources for trees. Our results revealed the impacts of disturbance density on forest community structure and could provide theoretical basis for forest management.