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You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically.Results: After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count; biochemical indicators of blood serum, organ coefficient, and oxidation and antioxidation indicators; and no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung through histopathological examination.Conclusion: Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our work lays a solid foundation for further biomedical applications of NIR QDs-RGD. Keywords: nanotechnology, RGD peptides, integrin αvß3, quantum dots, intravenous injection, toxicity

The NLRP3 inflammasome plays a pivotal role in the progression of inflammatory diseases. Mitochondrial damage, oxidative stress and mitochondrial DNA (mtDNA) leak are the key upstream factors for NLRP3 inflammasome activation. Nepetin (Nep), a naturally occurring flavonoid found with anti-inflammatory properties; however, whether it can affect the NLRP3 inflammasome activation and its precise anti-inflammatory mechanism remains unclear. In this study, we demonstrated that Nep enhances PINK1-mediated ubiquitin phosphorylation, which promotes mitophagy and subsequently inhibits NLRP3 inflammasome activation and pyroptosis in macrophages. The administration of Nep to macrophages alleviated of mitochondrial damage, reduced mitochondrial superoxide production, restored mitochondrial membrane potential and prevented the mtDNA leakage. These findings provide compelling evidence for the antioxidant effect of Nep. Furthermore, the pivotal function of mitophagy in the NLRP3 inflammasome inhibitory impact of Nep was substantiated through the utilisation of mitophagy inhibitors and siRNA techniques. Notably, Nep increased survival and reduced organ damage in mice with systemic inflammation by inhibiting NLRP3 inflammasome activation. In addition, Nep suppressed NLRP3 inflammasome activation in obese mice, which led to reduced white adipose and liver inflammation, thereby ameliorating insulin resistance. In conclusion, our findings suggest that Nep is a potent NLRP3 inflammasome inhibitor and a promising candidate for the development of anti-inflammatory therapies., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD)., Methods: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot., Results: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01)., Conclusion: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therapeutic resistance of common hematological malignancies. Furthermore, the review delves into the prognostic significance of circRNAs, underscoring their potential in predicting disease outcomes and treatment response. Given their extensive involvement in cancer biology, circRNAs present a frontier for novel therapeutic strategies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Infections in patients with hematological malignancies (HM) are a significant cause of morbidity and mortality. Timely and effective empirical anti-infective treatment can reduce the infection-related mortality rate. Targeted next-generation sequencing (tNGS) offers a rapid diagnostic approach for identifying diverse pathogens in these patients. However, relevant research is still limited to adult patients with HM., Methods: We conducted a retrospective analysis of adult HM patients admitted to our hospital from March 2023 to September 2023, focusing on their clinical characteristics and the results of both tNGS and conventional microbiological tests (CMTs). We evaluated the performance of tNGS and CMTs in pathogenic diagnosis and described the distribution characteristics of pathogens in adult HM patients with infections., Results: The study included 209 samples collected from 137 patients. Results showed that the overall pathogen detection rate differed significantly between tNGS and CMTs (60.3% vs. 24.4%, p  < 0.001). The sensitivity (69.7% vs. 35.9%), negative predictive value (NPV) (48.2% vs. 42.4%), and accuracy (66.5% vs. 56.5%) of pathogen detection were notably superior with tNGS compared to CMTs. Among the 142 samples with clinically diagnosed infections, tNGS combined with CMTs identified a definite or probable microbial etiology in 114 samples (80.3%). Of the 36 samples with concordant positive results from both tNGS and CMTs, 72.2% (26/36) exhibited full or partial agreement. Our study further showed the highest detection rate for viral infections (57.0%), predominantly for Epstein-Barr virus (DNA-V, 18.3%). Followed by bacterial infections (46.5%), the detection rate of Gram-negative bacteria (G + , 35.9%) was higher than that of Gram-positive bacteria (G - , 21.8%) in this study. Klebsiella pneumoniae (G - , 12.7%) had the highest detection rate among these emerging bacteria, followed by Pseudomonas aeruginosa (G - , 10.6%) and Enterococcus faecium (G + , 7.7%). Bacterial-viral coinfections were the most common type of mixed infection (35.5%)., Conclusion: In conclusion, tNGS outperforms CMTs in both sensitivity and pathogen spectrum. Therefore, it can serve as an adjunct to CMTs to facilitate the precise adjustment of anti-infective regimens for adult HM patients. Our findings establish a basis for formulating empirical anti-infective therapy strategies tailored to the pathogen distribution in this patient population., 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 © 2024 Xu, Cui, Wang, Nan, Yang, Bai and Shi.)

This paper introduces a novel digital triangular-trapezoidal double-channel shaping algorithm to enhance the counting rate of resistive anode detectors. The algorithm is based on the trapezoidal shaping algorithm and improves it. At the extreme counting rate, the trapezoidal shaping algorithm cannot alleviate the pulse pileup, so the counting rate cannot meet the requirements of a high performance detector. The triangular-trapezoidal double-channel shaping algorithm is introduced in the resistance anode detector, which can replace the trapezoidal shaping filtering algorithm to process the output signal of the resistance anode detector and obtain the single photon position information. This improvement improves the counting rate of the resistor anode detector and reduces the resolution degradation caused by pulse pileup. The algorithm is simulated by System Generator software and implemented on FPGA (field programmable gate array). The triangular-trapezoidal double-channel shaping algorithm presented in this paper plays an important role in reducing electronic noise and pulse pileup. The algorithm is subjected to simulation testing, and it can recognize signals with a minimum pulse interval of 1 µs and counting rate up to 1000 kcps., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury., Methods: Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed., Results: Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-β/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2)., Conclusions: This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

The environmental impact from the waste disposal has been widely concerned around the world. The conversion of wastes to useful resources is important for the sustainable society. As a typical family of wastes, biomass materials basically composed of collagen, protein and lignin are considered as useful resources for recycle and reuse. In recent years, the development of carbon material derived from biomasses, such as plants, crops, animals and their application in electrochemical energy storage have attracted extensive attention. Through the selection of the appropriate biomass, the optimization of the activation method and the control of the pyrolysis temperatures, carbon materials with desired features, such as high-specific surface area, variable porous framework, and controllable heteroatom-doping have been fabricated. Herein, this review summarized the preparation methods, morphologies, heteroatoms doping in the plant/animal-derived carbonaceous materials, and their application as electrode materials for secondary batteries and supercapacitors, and as electrode support for lithium-sulfur batteries. The challenges and prospects for the controllable synthesis and large-scale application of biomass-derived carbonaceous materials have also been outlooked., (© 2024 Wiley‐VCH GmbH.)

Background: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals., Case Summary: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle., Conclusion: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study aimed to explore the mechanism of Shexiang Tongxin Dropping Pills(STDP) in treating diabetic cardiomyopathy(DCM) based on network pharmacology, molecular docking, and animal experiments. BATMAN, TCMSP, and GeneCards were searched for the active ingredients and targets of STDP against DCM. STRING and Cytoscape were used to build the protein-protein interaction(PPI) network and &quot;drug-active ingredient-target&quot; network. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of the targets were carried out based on DAVID. The molecular docking of key receptor proteins with corresponding active ingredients was performed using AutoDock Vina. The rat model of DCM was established by a high-fat diet combined with intraperitoneal injection of streptozotocin. Rats were assigned into control, model, low-(20 mg·kg~(-1)) and high-dose(40 mg·kg~(-1)) STDP, and metformin(200 mg·kg~(-1)) groups. After 8 weeks of continuous administration, the cardiac function, myocardial pathological changes, and myocardial collagen fiber deposition of rats in each group were detected by echocardiography, hematoxylin-eosin(HE) staining, and Sirius red staining, respectively. The myocardial hypertrophy was detected by WGA staining. The expression levels of p38 mitogen-activated protein kinase(p38), phosphorylation-p38(p-p38), c-Jun N-terminal kinase(JNK), phosphorylation-JNK(p-JNK), caspase-3, and C-caspase-3 in the myocardial tissue of rats in each group were measured by Western blot. The network pharmacology predicted 199 active ingredients and 1 655 targets of STDP and 463 targets of DCM. One hundred and thirty-four potential targets of STDP for treating DCM were obtained, and the AGE-RAGE signaling pathway in diabetic complications was screened out. Molecular docking results showed that miltirone, dehydromiltirone, and tryptanthrin had strong binding affinity with RAGE. The results of animal experiments confirmed that STDP effectively protected the cardiac function of DCM rats. Compared with the DCM model group, the STDP groups showed significantly down-regulated protein levels of p-p38, p-JNK, and C-caspase-3. To sum up, STDP may protect the cardiac function of DCM rats by regulating the AGE-RAGE signaling pathway.

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP ( n =6 453, 93.6%) or AP ( n =440, 6.4%) receiving initial imatinib ( n =4 906, 71.2%), nilotinib ( n =1 157, 16.8%), dasatinib ( n =298, 4.3%) or flumatinib ( n =532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n =1 055, 15.3%), intolerance ( n =248, 3.6%), pursuit of better efficacy ( n =168, 2.4%), economic or other reasons ( n =110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P <0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P =0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Reservoir computing is an effective model for learning and predicting nonlinear and chaotic dynamical systems; however, there remains a challenge in achieving a more dependable evolution for such systems. Based on the foundation of Koopman operator theory, considering the effectiveness of the sparse identification of nonlinear dynamics algorithm to construct candidate nonlinear libraries in the application of nonlinear data, an alternative reservoir computing method is proposed, which creates the linear Hilbert space of the nonlinear system by including nonlinear terms in the optimization process of reservoir computing, allowing for the application of linear optimization. We introduce an implementation that incorporates a polynomial transformation of arbitrary order when fitting the readout matrix. Constructing polynomial libraries with reservoir-state vectors as elements enhances the nonlinear representation of reservoir states and more easily captures the complexity of nonlinear systems. The Lorenz-63 system, the Lorenz-96 system, and the Kuramoto-Sivashinsky equation are used to validate the effectiveness of constructing polynomial libraries for reservoir states in the field of state-evolution prediction of nonlinear and chaotic dynamical systems. This study not only promotes the theoretical study of reservoir computing, but also provides a theoretical and practical method for the prediction of nonlinear and chaotic dynamical system evolution.

Objective: Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo ., Methods: Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg∙body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings., Results: In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group ( P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h ( P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h ( P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed., Conclusion: Nanoplastics translocated rapidly to observed organs/tissues through blood circulation; however, only small amounts of MPs could penetrate the organs., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Aim: Many persons living with dementia (PLWD) reside in the community and are cared for by family members. The aim of this qualitative study was to gain an understanding the enrichment process for family caregivers of PLWD in Taiwan., Design: A grounded theory approach with face-to-face semi-structured interviews was conducted with family caregivers of PLWD in Taiwan., Methods: Interview data from 30 family caregivers of PLWD recruited from dementia clinics or support groups in Taiwan were obtained from the first wave of a larger study conducted from January 2018 to September 2021. Glaser's grounded theory approach with theoretical sampling was used to understand the enrichment process of family caregivers of PLWD., Results: Analysis indicated the core category that characterized the process of enrichment was 'holding together'. Caregivers were able to maintain their connection to the person with dementia through activities that deepened their relationship and strengthened their bond. 'Holding together' included four components: maintaining continuity, creative interactions, interacting with humour and sharing pleasurable activities. Through these components, family caregivers generated positive interactions and relationships with the person living with dementia and sustained their motivation for caregiving. Three modifying elements facilitated or impeded the process of holding together: 'previous daily interactions', 'caregiving beliefs' and 'filial piety'., Conclusion: Through the enrichment process of 'holding together', family caregivers used different strategies to conduct pleasurable and meaningful activities with the person living with dementia to maintain and improve their relationship and enhance their happiness in life., Impact: To facilitate the enrichment process, health care providers should encourage activities between family caregivers and PLWD that promote continuity, increase interactions, provide humour and foster pleasurable activities., Reporting Method: This study adhered to the COREQ guideline checklist., Patient or Public Contribution: No patient or public contribution., (© 2023 John Wiley & Sons Ltd.)

Background: Lung ultrasound score (LUS) is a clinical index used to measure lung injury, but its clinical value in patients after cardiopulmonary resuscitation (CPR) remains relatively unknown. The purpose of this study was to investigate the clinical value of LUS in patients after CPR., Methods: This retrospective study included a total of 34 patients older than 18 years with a nontraumatic cause of in-hospital cardiac arrest, who received standard resuscitation and achieved return of spontaneous circulation (ROSC). All patients underwent bedside lung ultrasound examination within half an hour once ROSC was achieved, and LUSs were calculated. The study included patient death as the endpoint event., Results: Compared with the group with lower LUSs, the patients with higher LUSs had a lower oxygenation index, longer duration of CPR, and lower 72 h survival rate. The initial LUS had good clinical value in predicting the secondary outcomes of CPR (adjusted odds ratio (aOR): 1.353, 95% confidence interval (CI): 1.018-1.797, and P  = 0.037) and 72 h survival rate of patients who underwent CPR (aOR: 1.145, 95% CI: 1.014-1.294, and P  = 0.029)., Conclusions: LUS was shown to be helpful and had a prognostic value in patients after CPR., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Yi-Ling Zhang et al.)

Background and Aim: Healthcare-associated infections (HAIs) after pancreaticoduodenectomy (PD) are one of the common postoperative complications. This study aims to investigate the epidemiology of postoperative HAIs in patients with open pancreaticoduodenectomy (OPD) and robotic pancreaticoduodenectomy (RPD)., Methods: This retrospective cohort study described the trend of HAIs in patients undergoing PD from January 2013 to December 2022 at a tertiary hospital. Patients were divided into OPD and RPD, and the HAIs and outcomes were compared., Results: Among 2632 patients who underwent PD, 230 (8.7%, 95% confidence interval [CI] 7.7-9.9%) were diagnosed with HAIs, with a decreasing trend from 2013 to 2022 (P < 0.001 for trend). The incidence of postoperative HAIs was significantly higher in patients with OPD than RPD (9.6% vs 5.8%; P = 0.003). The incidence of HAIs for patients with OPD showed a decreasing trend (P = 0.001 for trend), and the trend for RPD was not significant (P = 0.554 for trend). Logistic regression showed that RPD was significantly associated with postoperative HAIs after adjusting for covariates (adjusted odds ratio = 0.654; 95% CI 0.443-0.965; P = 0.032), especially in the subgroup of patients without preoperative biliary drainage (adjusted odds ratio = 0.486; 95% CI 0.292-0.809; P = 0.006). Regarding clinical outcomes, RPD has a shorter length of stay and a more expensive charge than OPD (all P < 0.05)., Conclusion: Postoperative HAIs in patients with PD showed a decreasing trend in recent years, especially in OPD. RPD was significantly associated with reduced postoperative HAIs and length of stay, although the charge is more expensive. Attention should be paid to postoperative HAIs in OPD, and it is imperative to continue reducing the costs of RPD., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A new strategy is developed herein to improve the solid fluorescence of thiazolothiazole viologen by using the ZnCl 4 2- cluster as a scaffold to hinder π-stacking. Importantly, the Cl···H bonds are formed in the solid state to sustain the framework and can be automatically dissociated when dissolved in H 2 O, thus having no impact on the strong emission in aqueous solution. As such, the first case of organic-inorganic viologen-zinc halide named 4PV·ZnCl 4 was designed and synthesized, and a significant increase in photoluminescence quantum yield (Φ F ) is realized from 4PV·2Br (Φ F = 0%) to 4PV·ZnCl 4 (Φ F = 27.0%) in solid and from 97% to 98% in H 2 O. 4PV·ZnCl 4 also displays pH stimuli-responsive naked-eye chromic behavior and photoluminescence with different coloring states and intensities. The multifunctional performance of 4PV·ZnCl 4 provides a prerequisite for carrying different information, expanding their promising application in multilevel information encryption.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib ( n =4 380) or flumatinib ( n =453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P <0.001), whereas the PFS ( P =0.230) and OS ( P =0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

To improve the interfacial bonding of dissimilar composites, the interaction mechanism between the surface state and severe plastic deformation to strengthen the interfacial bonding strength was revealed. In this study, the different surface states of the steel strip were designed by louver blade grinding (LBG) and diamond bowl grinding (DBG), and the cold-rolled composite method was developed to prepare the brass/carbon steel composite strips. The results show that the steel surface after DBG has a large roughness of 9.79 μm, a hard hardening layer of 6.2 GPa, and high cleanliness of 1.34 atomic % oxygen content, while that after LBG has a roughness of 1.31 μm, a hardening layer of 4.2 GPa, and an oxygen content of 2.37 atomic %. The large roughness promotes the breaking of the hardening layer; the hardening layer is beneficial to obtain sufficient interfacial stress to expose the fresh metal; and the high cleanliness reduces the barrier to the fresh metal and contributes to the bonding of the fresh metal. The interface of the cold-rolled brass/carbon steel composite strip after LBG and DBG is mechanical bonding and metallurgical bonding, respectively. In the process of the cold-rolling composite, large shear deformation occurs at the interface of brass and steel, resulting in a high concentration of vacancy and dislocation defects, which provides a channel for interdiffusion of atoms at the interface. Under the diffusion driving force provided by the cold-rolling shear deformation heat, a nanodiffusion layer with a thickness of 60 nm and high interfacial bond strength was formed.

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

The dark-colored viologen radical cations are unstable in air and easily fade, thus greatly limiting their applications. If a suitable substituent is introduced into the structure, it will have the dual function of chromism and luminescence, which will broaden its application field. Here, Vio1·2Cl and Vio2·2Br were synthesized by introducing aromatic acetophenone and naphthophenone substituents into the viologen structure. The keto group (-CH 2 CO-) on the substituents is prone to isomerize into the enol structure (-CH[double bond, length as m-dash]COH-) in organic solvents, especially in DMSO, resulting in a larger conjugated system to stabilize the molecular structure and enhance fluorescence. The time-dependent fluorescence spectrum shows obvious keto-to-enol isomerization-induced fluorescence enhancement. The quantum yield also increased significantly ( T = 1 day, Φ Vio1 = 25.81%, Φ Vio2 = 41.44%; T = 7 days, Φ Vio1 = 31.48%, and Φ Vio2 = 54.40%) in DMSO. The NMR and ESI-MS data at different times further confirmed that the fluorescence enhancement was caused by isomerization, and no other fluorescent impurities were produced in solution. DFT calculations show that the enol form is almost coplanar throughout the molecular structure, which is conducive to stabilizing the structure and enhancing fluorescence. The fluorescence emission peaks of the keto and enol structures of Vio1 2+ and Vio2 2+ were at 416-417 nm and 563-582 nm, respectively. The fluorescence relative oscillator strength of Vio1 2+ and Vio2 2+ enol structures is significantly higher than that of keto structures ( f value changes from 1.53 to 2.63 for Vio1 2+ and from 1.62 to 2.81 for Vio2 2+ ), indicating stronger fluorescence emission of the enol structure. The calculated results are in good agreement with the experimental results. Vio1·2Cl and Vio2·2Br are the first examples of isomerization-induced fluorescence enhancement of viologen derivatives, which shows strong solvatofluorochromism under UV light, making up for the disadvantage that it is easy for a viologen radical to fade in air, and providing a new strategy for designing and synthesizing viologen materials with strong fluorescence., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Post-stroke spasticity is a cause of gait dysfunction and disability. Focal vibration (FV) of agonist-antagonist upper limb muscle pairs reduces flexor spasticity; however, its effects on ankle plantarflexor spasticity are uncertain., Objective: To assess the effects of focal vibration administered by a trained operator to the ankle plantarflexor and dorsiflexor muscles on post-stroke lower limb spasticity., Methods: A randomized, single-blind controlled trial of 64 participants with stroke and plantarflexor spasticity assigned to 3 groups by centralized, computer-generated randomization (1:1:1): 1) physiotherapy alone (CON), 2) physiotherapy+gastrocnemius vibration (FV&#95;GM) and 3) physiotherapy+tibialis anterior vibration (FV&#95;TA). Physiotherapists and assessors were blinded to group assignment. The experimental groups underwent 15, 20-min vibration sessions at 40 Hz. We performed evaluations at baseline and after the final treatment: Modified Ashworth Scale (MAS), Clonus scale, Functional Ambulation Categories (FAC), Fugl-Meyer Assessment - Lower Extremity (FMA&#95;LE), Modified Barthel Index (MBI), and electromyography and ultrasound elastography. Primary outcome was remission rate (number and proportion of participants) of the MAS., Results: MAS remission rate was higher in FV&#95;GM and FV&#95;TA than CON groups (CON vs. FV&#95;GM: p=0.009, odds ratio 0.15 [95% confidence interval 0.03-0.67]; CON vs. FV&#95;TA: p=0.002, 0.12 [0.03-0.51]). Remission rate was higher in the experimental than CON groups for the Clonus scale (CON vs. FV&#95;GM: p<0.001, OR 0.07 [95% CI 0.01-0.31]; CON vs. FV&#95;TA: p=0.006, 0.14 [95% CI 0.03-0.61]). FAC remission rate was higher in the FV&#95;TA than the CON (p=0.009, 0.18 [0.05-0.68]) and FV&#95;GM (p=0.014, 0.27 [0.07-0.99]) groups. Ultrasound variables of the paretic medial gastrocnemius decreased more in FV&#95;GM than CON and FV&#95;TA groups (shear modulus: p=0.006; shear wave velocity: p=0.008)., Conclusions: Focal vibration reduced post-stroke spasticity of the plantarflexor muscles. Vibration of the tibialis anterior improved ambulation more than vibration of the gastrocnemius or physiotherapy alone. Gastrocnemius vibration may reduce spasticity by changing muscle stiffness., Competing Interests: Declaration of Competing Interest None declared No preprints available, (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Common carp are among the oldest domesticated fish in the world. As such, there are many food and ornamental carp strains with abundant phenotypic variations due to natural and artificial selection. Hebao red carp (HB, Cyprinus carpio wuyuanensis ), an indigenous strain in China, is renowned for its unique body morphology and reddish skin. To reveal the genetic basis underlying the distinct skin color of HB, we constructed an improved high-fidelity (HiFi) HB genome with good contiguity, completeness, and correctness. Genome structure comparison was conducted between HB and a representative wild strain, Yellow River carp (YR, C. carpio haematopterus ), to identify structural variants and genes under positive selection. Signatures of artificial selection during domestication were identified in HB and YR populations, while phenotype mapping was performed in a segregating population generated by HB×YR crosses. Body color in HB was associated with regions with fixed mutations. The simultaneous mutation and superposition of a pair of homologous genes ( mitfa ) in chromosomes A06 and B06 conferred the reddish color in domesticated HB. Transcriptome analysis of common carp with different alleles of the mitfa mutation confirmed that gene duplication can buffer the deleterious effects of mutation in allotetraploids. This study provides new insights into genotype-phenotype associations in allotetraploid species and lays a foundation for future breeding of common carp.

Background: Depressive moods are commonly seen in patients who receive haemodialysis. This can cause a lack of compliance in their treatment procedures and increase the rate of hospitalization. This study aimed to investigate the relationship between social support and degree of depression in middle-aged and elderly patients undergoing haemodialysis and the predictors of depressive symptoms., Methods: A cross-sectional correlational study was designed with a structured questionnaire survey. Patients over 40 years of age were included from five haemodialysis centres. Measures embraced a demographic and clinical characteristics questionnaire, the Centre for Epidemiologic Studies Depression Scale, and the Personal Resource Questionnaire 2000. Statistical analysis was performed using hierarchical multiple regression analysis., Results: A total of 179 patients over 40 years of age were included from five haemodialysis centres in the analysis. The mean CES-D score was 19.0(12.3); the majority of participants (60.3%) had a CES-D score ≥ 15, indicating likely depressive status. The mean PRQ2000 score was 75.7(15.9). The proportional mean of the PRQ2000 was 72.11%, indicating moderate social support for participants in this study. Data disclosed that marital status, number of comorbidities, exercise behaviour, and social support could significantly predict depressive symptoms; total explanatory variance was 31.3%., Conclusion: Health care professionals should identify those at high risk of depressive symptoms when they provide care to the middle-aged and elderly patients undergoing haemodialysis. These findings may lead to greater insights into the nursing and rehabilitative care of patients treated by chronic maintenance haemodialysis., (© 2023. The Author(s).)

A crucial challenge encountered in diverse areas of engineering applications involves speculating the governing equations based upon partial observations. On this basis, a variant of the sparse identification of nonlinear dynamics (SINDy) algorithm is developed. First, the Akaike information criterion (AIC) is integrated to enforce model selection by hierarchically ranking the most informative model from several manageable candidate models. This integration avoids restricting the number of candidate models, which is a disadvantage of the traditional methods for model selection. The subsequent procedure expands the structure of dynamics from ordinary differential equations (ODEs) to partial differential equations (PDEs), while group sparsity is employed to identify the nonconstant coefficients of partial differential equations. Of practical consideration within an integrated frame is data processing, which tends to treat noise separate from signals and tends to parametrize the noise probability distribution. In particular, the coefficients of a species of canonical ODEs and PDEs, such as the Van der Pol , Rössler , Burgers' and Kuramoto-Sivashinsky equations , can be identified correctly with the introduction of noise. Furthermore, except for normal noise, the proposed approach is able to capture the distribution of uniform noise. In accordance with the results of the experiments, the computational speed is markedly advanced and possesses robustness., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Brassinosteroids (BRs) are plant steroid hormones that are involved in the regulation of plant growth and development as well as environmental adaptation. The discovery of new BR derivatives is beneficial to their biosynthesis and regulation mechanisms research. However, there are few reports on the methods for exploring new BRs, and the existing methods tend to lack coverage. In this work, we established a comprehensive, highly sensitive and selective structure-oriented method for the screening and structural identification of potential BRs in plants using chemical isotope labeling-assisted liquid chromatography-high resolution mass spectrometry (CL-LC-HRMS). The potential BRs were speculated according to the structural features of the reported BRs, and those speculated BRs containing cis-diol groups were labeled by isotope reagents of 2-methyl-4-phenylaminomethylphenylboronic acid (2-methyl-4-PAMBA) and 2-methyl-4-PAMBA-d 5 to improve the sensitivity and selectivity of MS detection. In addition, the fragmentation of 2-methyl-4-PAMBA-labeled BRs via collision-induced dissociation (CID) led to the generation of reporter ions, which contributed to specific screening of potential BRs. In-depth structure of potential BRs was elucidated by analyzing multistage MS (MS n ) fragmentation patterns. Using our proposed method, a total of 16 potential BRs were detected from plant samples including 5 new ones, of which one new BR derivative was identified as 2-deoxy-3-epi-6-deoxy-dolichosterone, and this new BR may be involved in the biosynthesis of BRs as precursor of 6-deoxo-dolichosterone. The method developed in this work is promising for screening and identifying new BR derivatives in plants, thereby supplementing the biosynthesis pathway of BRs., Competing Interests: Declaration of competing Interest The authors declare no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study aims to investigate the effect of Shexiang Tongxin Dropping Pills(STDP) on angiogenesis in type 2 diabetic rats. Thirty-two healthy male SD rats were randomized into a control group(n=6) and a type 2 diabetes mellitus(T2 D) group(n=26). The T2 DM rat model was established with a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ). The model rats were randomized into a model group, a metformin group(200 mg·kg~(-1)·d~(-1)), a high-dose STDP group(40 mg·kg~(-1)·d~(-1)), and a low-dose STDP group(20 mg·kg~(-1)·d~(-1)). The corresponding agents were administered continuously for 8 weeks. The cardiac function indexes were detected by ultrasound at the experiment endpoint, and the myocardial pathological changes were observed via hematoxylin-eosin(HE) staining. The myocardial collagen fiber deposition was detected by sirius red staining, the myocardial microvascular density by immunohistochemistry, and the myocardial hypertrophy by immunofluorescence assay. Western blot was employed to measure the protein levels of vascular endothelial growth factor(VEGF), phosphorylated vascular endothelial growth factor receptor 2(p-VEGFR2), angiogenin-1(Ang1), and TEK tyrosine kinase endothelial(Tie2) in the myocardial tissue. Compared with the model group, STDP improved the left ventricular ejection fraction(EF) and fractional shortening(FS)(P&lt;0.05), alleivated the arrangement disorder of myocardial cells and local myocardial fiber rupture. Sirius red staining showed that STDP, especially the high-dose group(P&lt;0.01), repaired the deposition of myocardial collagen fibers in the model group. The results of immunohistochemistry showed that the cluster of differentiation 31(CD31) expression in myocardial tissue of the STDP groups was higher than that of the model group(P&lt;0.01). The immunofluorescence results showed that STDP mitigated the hypertrophy of myocardial cells(P&lt;0.01). Furthermore, STDP up-regulated the protein levels of VEGF, p-VEGFR2, Angl, and Tie2 compared with the model group(P&lt;0.01). In conclusion, STDP can effectively promote angiogenesis and improve cardiac function in type 2 diabetic rats by up-regulating the expression of VEGF, p-VEGFR2, Ang1, and Tie2.

Objective: This study was designed to provide the evidences on the toxicokinetics of microplastics (MPs) and nanoplastics (NPs) in the bodies of mammals., Methods: 100 nm, 3 μm, and 10 μm fluorescent polystyrene (PS) beads were administered to mice once by gavage at a dose of 200 mg/kg body weight. The levels and change of fluorescence intensity in samples of blood, subcutaneous fat, perirenal fat, peritesticular fat, cerebrum, cerebellum, testis, and epididymis were measured at 0.5, 1, 2, and 4 h after administration using an IVIS Spectrum small-animal imaging system. Histological examination, confocal laser scanning, and transmission electron microscope were performed to corroborate the findings., Results: After confirming fluorescent dye leaching and impact of pH value, increased levels of fluorescence intensity in blood, all adipose tissues examined, cerebrum, cerebellum, and testis were measured in the 100 nm group, but not in the 3 and 10 μm groups except in the cerebellum and testis at 4 h for the 3 μm PS beads. The presence of PS beads was further corroborated., Conclusion: After a single oral exposure, NPs are absorbed rapidly in the blood, accumulate in adipose tissues, and penetrate the blood-brain/testis barriers. As expected, the toxicokinetics of MPs is significantly size-dependent in mammals., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Abscisic acid (ABA) hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance. Here, we discover a new downstream catabolite of neophaseic acid (neoPA) in the ABA 9'-hydroxyl pathway and identify it as epi-neodihydrophaseic acid (epi-neoDPA) by comparing its accurate mass, retention time, and MS n spectra with those of our chemically synthesized epi-neoDPA. Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity. In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1 (neoPA reductase 1) identified from Arabidopsis converts neoPA into epi-neoDPA. Site-directed mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1. Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants, whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines, suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Retinoic acids (RAs), an important class of fatty acid derived from vitamin A, are closely associated with various human diseases including cancer. Hence, determination of endogenous RAs would help to uncover the mechanisms underlying RAs-related diseases. However, accurate quantification of RAs is still a challenge due to their high structure similarity, low abundance in biological samples and the lack of isotope internal standards (ISs). In this study, a liquid chromatography-mass spectrometry (LC-MS) method with high-sensitivity and high-throughput was developed to simultaneously determine 5 RAs (all-trans-retinoic acid, 13-cis-retinoic acid, 9,13-cis-retinoic acid, all-trans-4-oxoretinoic acid and 4-hydroxy-retinoic acid) in human serum. In the method, three derivatization reagents, N, N-dimethylethylenediamine (DMED), d 4 -N,N-dimethylethylenediamine (d 4 -DMED) and 13 C 2 -N,N-dimethylethylenediamine ( 13 C 2 -DMED), were used for triple chemical derivatization of RAs, thus the detection sensitivity and analysis throughput of endogenous RAs could be achieved. Benefiting from the developed strategy, the analysis throughput was enhanced and the detection sensitivity of RAs was increased by 14-398 folds. The limits of quantification (LOQs) of RAs were found to be between 8.4 and 130 pg/mL, which were better than previously reported methods. Good linearities of RAs were obtained with determination coefficient (R 2 ) ranging from 0.9774 to 0.9999. The intra- and inter-day relative standard deviations (RSDs) were below 11.7% and 12.7%, respectively, indicating the acceptable reproducibility of the method. Using the developed method, we successfully quantified 4 RAs (all-trans-retinoic acid, 13-cis-retinoic acid, 9,13-cis-retinoic acid and all-trans-4-oxoretinoic acid) in health controls and cancer patient serum samples. Furthermore, t-test analysis showed that the concentration of three RAs (all-trans-retinoic acid, 13-cis-retinoic acid and all-trans-4-oxoretinoic acid) in cancer patient serum samples were significantly decreased compared with health controls, which indicated that RAs might play an important role in the formation and development of cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical roles in immunity and other cellular functions. To investigate the role of USPs in alphaherpesvirus replication, we assessed 13 USP inhibitors for PRV replication. Our data showed that all the tested compounds inhibited PRV replication, with the USP14 inhibitor b-AP15 exhibiting the most dramatic effect. Ablation of USP14 also influenced PRV replication, whereas replenishment of USP14 in USP14 null cells restored viral replication. Although inhibition of USP14 induced the K63-linked ubiquitination of PRV VP16 protein, its degradation was not dependent on the proteasome. USP14 directly bound to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection. Moreover, USP14 inactivation stimulated EIF2AK3/PERK- and ERN1/IRE1-mediated signaling pathways, which were responsible for VP16 degradation through SQSTM1/p62-mediated selective macroautophagy/autophagy. Ectopic expression of non-ubiquitinated VP16 fully rescued PRV replication. Challenge of mice with b-AP15 activated ER stress and autophagy and inhibited PRV infection in vivo . Our results suggested that USP14 was a potential therapeutic target to treat alphaherpesvirus-induced infectious diseases. Abbreviations ATF4: activating transcription factor 4; ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; CCK-8: cell counting kit-8; Co-IP: co-immunoprecipitation; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR associated system 9; DDIT3/CHOP: DNA-damage inducible transcript 3; DNAJB9/ERdj4: DnaJ heat shock protein family (Hsp40) member B9; DUBs: deubiquitinases; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EP0: ubiquitin E3 ligase ICP0; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; FOXO1: forkhead box O1; FRET: Förster resonance energy transfer; HSPA5/BiP: heat shock protein 5; HSV: herpes simplex virus; IE180: transcriptional regulator ICP4; MAP1LC3/LC3: microtube-associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; PRV: pseudorabies virus; PRV gB: PRV glycoprotein B; PRV gE: PRV glycoprotein E; qRT-PCR: quantitative real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID 50 : tissue culture infective dose; UB: ubiquitin; UBA: ubiquitin-associated domain; UBL: ubiquitin-like domain; UL9: DNA replication origin-binding helicase; UPR: unfolded protein response; USPs: ubiquitin-specific proteases; VHS: virion host shutoff; VP16: viral protein 16; XBP1: X-box binding protein 1; XBP1s: small XBP1; XBP1(t): XBP1-total.

In this study, a screening strategy was established based on ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry assisted by chemical isotope labeling (CIL-UPLC-HRMS) for screening and identifying abscisic acid (ABA) catabolites. Based on the structures of known ABA catabolites, this strategy first proposed the structures of catabolites to be discovered. Afterward, a pair of isotope reagents N , N -2-dimethylaminoethylamine (DMED) and d 4 -DMED were used as labeling reagents to label the carboxyl groups in ABA and its catabolites. Then, the mass-to-charge ratio ( m / z ) of DMED- and d 4 -DMED-labeled ABA catabolites was calculated based on the labeling schema. In light of the characteristic fragmentation patterns of the DMED-labeled standards of ABA and its catabolites, screening criteria were formulated. Using our strategy, ABA, t- ABA, and 18 ABA catabolites were identified from seven plant samples. Of the identified catabolites, 16 were known, and to our knowledge, 2 were previously unidentified. Our findings contribute to ABA catabolic network improvement.

A novel Gram-stain-negative, oxidase-positive, catalase-positive, non-motile, facultatively anaerobic, rod-shaped bacterium, designated WB101 T , was isolated from a marine solar saltern located in Wendeng, PR China. Strain WB101 T shared a high level of 16S rRNA gene sequence similarity with Rhodohalobacter barkolensis 15182 T (93.5%), R. halophilus JZ3C29 T (93.2%), and 'R. mucosus' 8A47 T (92.1%). Strain WB101 T formed a species-level branch within the genus Rhodohalobacter in both phylogenetic and phylogenomic topologies. The DNA G + C content was 42.0%. Strain WB101 T was found to have menaquinone-7 as the only respiratory quinone. The dominant cellular fatty acid (≥ 10%) was iso-C 15:0 . The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. Characterisation based on phylogenetic, physiological, and biochemical properties indicated that strain WB101 T represents a novel species of the genus Rhodohalobacter, and the name Rhodohalobacter sulfatireducens sp. nov. is proposed. The type strain is WB101 T (= KCTC 92204 T  = MCCC 1H00518 T )., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.

In this study, a highly sensitive method for analysis of 4 cyanogenic glycosides (CNGs) in cold-pressed flaxseed oil was developed by using cigarette filter fiber-based SPE and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The cold-pressed flaxseed oil was diluted with 5% (v/v) isopropanol/n-hexane solution and loaded to a cigarette filters fiber-based SPE column for CNG enrichment and purification. Under optimized conditions, four CNGs could be detected with limits of detection ranging from 1.3 to 4.4 pg/mL. The linear range was 0.05-50 ng/ml with a linear correlation coefficient (r) > 0.9935. CNG recovery ranged from 113% to 133%, and the relative standard deviation was between 0.8% and 20.5%. Finally, the proposed method was applied to the determination of CNGs in nine cold-pressed flaxseed oils., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We presented an effective and universal strategy for the improvement of luminophore's solid-state emission, i.e., macrocyclization-induced emission enhancement (MIEE), by linking luminophores through C(sp 3 ) bridges to give a macrocycle. Benzothiadiazole-based macrocycle (BT-LC) has been synthesized by a one-step condensation of the monomer 4,7-bis(2,4-dimethoxyphenyl)-2,1,3-benzothiadiazole (BT-M) with paraformaldehyde, catalyzed by Lewis acid. In comparison with the monomer, macrocycle BT-LC produces much more intense fluorescence in the solid state (Φ PL  = 99%) and exhibits better device performance in the application of OLEDs. Single-crystal analysis and theoretical simulations reveal that the monomer can return to the ground state through a minimum energy crossing point (MECP S1/S0 ), resulting in the decrease of fluorescence efficiency. For the macrocycle, its inherent structural rigidity prohibits this non-radiative relaxation process and promotes the radiative relaxation, therefore emitting intense fluorescence. More significantly, MIEE strategy has good universality that several macrocycles with different luminophores also display emission improvement., (© 2022. The Author(s).)

Melatonin is known to involve multiple physiological actions in plants. Herein, we found that exogenous melatonin inhibited the Arabidopsis seedling growth through the elevated abscisic acid (ABA) levels, and the elevated ABA was ascribed to the upregulation of 9-cis-epoxycarotenoid dioxygenase genes (NCEDs) in the ABA biosynthesis pathway. We also found that the overexpression lines of the melatonin receptor gene PMTR1 (also known as Cand2) yielded smaller seeds and germinated slower than the wild type, whereas PMTR1-knockout mutants produced larger seeds and germinated faster than the wild type. During the seed development, the accumulation peak of ABA was higher in the PMTR1-knockout mutant, while it was lower in the PMTR1-overexpression line than that in the wild type. In the dry seeds and imbibed seeds, the PMTR1-overexpression line accumulated higher ABA levels, while the PMTR1-knockout contained less ABA than the wild type. In summary, our findings suggest that PMTR1 is involved in ABA-mediated seed development and germination in Arabidopsis., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bile acids (BAs) are a type of gut microbiota-host cometabolites with abundant structural diversity, and they play critical roles in maintaining host-microbiota homeostasis. In this study, we developed a new N -(4-aminomethylphenyl) pyridinium (AMPP) derivatization-assisted alternating dual-collision energy scanning mass spectrometry (AMPP-dual-CE MS) method for the profiling of BAs derived from host-gut microbiota cometabolism in mice. Using the proposed method, we discovered two new types of amino acid conjugations (alanine conjugation and proline conjugation) and acetyl conjugation with host BAs, for the first time, from mouse intestine contents and feces. Additionally, we also determined and identified nine new leucine- and phenylalanine-conjugated BAs. These findings broaden our knowledge of the composition of the BA pool and provide insight into the mechanism of host-gut microbiota cometabolism of BAs.

Phaseic acid (PA), a main catabolite of abscisic acid (ABA), is structurally related to ABA and possesses ABA-like hormonal activity. However, the comprehensive metabolism pathway and roles of PA are not well understood. Here, using homologous alignment and expression pattern analysis, we identified in Arabidopsis the previously named CRL1 (Cinnamoyl coA: NADP oxidoreductase-like 1) as a PA reductase that catalyses PA to dihydrophaseic acid. The function of CRL1 and the potential role of PA were studied in transgenic CRL1 plants. Overexpression of CRL1 resulted in decreased ABA sensitivity in seed germination and attenuated drought tolerance. In contrast, increased ABA sensitivity and elevated drought tolerance was observed in down-regulated and loss-of-function crl1 mutants. Tyr162 in the conserved motif is the key residue in CRL1 to catalyse PA. Accelerated seed germination and earlier flowering phenotype were also observed in overexpressing lines, while retarded seed germination and delayed flowering occurred in crl1 mutants which accumulated more PA, but less dihydrophaseic acid than the wild type. This study demonstrates that PA plays diverse functions in drought tolerance, seed germination and flowering in an ABA-like manner, which may increase the adaptive plasticity of plants., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Puerarin is a predominant component of Radix Puerarin . Despite its anti-tumor and anti-virus effects and efficacy in improving cardiovascular or cerebrovascular diseases and preventing osteoporosis, it has been shown to protect against diabetes and its complications. This review summarizes the current knowledge on Puerarin in diabetes and related complications, aiming to provide an overview of antidiabetic mechanisms of Puerarin and new targets for treatment., 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 © 2022 Bai, Han, Qian and Wang.)

Agrobiodiversity conservation is vital for achieving sustainability, but empirical studies on the effects of different practices or measures on crop diversity are rare. This study aims to estimate the effects of raising conservation awareness (RCA), building diversity blocks (BDB), and their combination on crop diversity among 240 randomly selected households surrounding the Rupa Lake Watershed in Nepal. Based on descriptive analysis and multiple regression models, the results indicate that the two single measures had no significant effect on the numbers of crop species and varieties grown by households in 2018. However, the combination of RCA and BDB had a significantly positive effect on the number of crop varieties, especially for grain and vegetable crops. Considering that these crops are essential in the daily lives of local people, the results indicate that a strategy that combines both awareness raising and on-farm conservation measures can generate higher crop diversity and better serve the climate-resilient livelihoods of people in mountainous areas., (© The Author(s) 2022.)

To clarify the key quality attributes of substance benchmarks in Danggui Buxue Decoction(DBD), this study prepared 21 batches of DBD substance benchmarks, and established two methods for detecting their fingerprints, followed by the identification of peak attribution and similarity range as well as the determination of extract and transfer rate ranges and contents of index components ferulic acid, calycosin-7-O-β-D-glucoside, and astragaloside Ⅳ. The mass fractions and transfer rates of DBD substance benchmarks from different batches were calculated as follows: ferulic acid(index component in Angelicae Sinensis Radix): 0.037%-0.084% and 31.41%-98.88%; astragaloside Ⅳ(index component in Astragali Radix): 0.021%-0.059% and 32.18%-118.57%; calycosin-7-O-β-D-glucoside: 0.002%-0.023% and 11.51%-45.65%, with the extract rate being 18.4%-36.1%. The similarity of fingerprints among 21 batches of DBD substance benchmarks was all higher than 0.9. The quality control method for DBD substance benchmarks was preliminarily established based on the HPLC fingerprint analysis and index component determination, which has provided a basis for the subsequent development of DBD and the quality control of novel related preparations.

Background: Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines. Design: A systematic review and expert consensus. Methods: A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine. Results: Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga). Conclusions: Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five-ten years., 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 © 2021 Zhang, Hu, Xiong, Peng, Hu, Kong, Wang, Guo, Bi, Li, Ao, Wang, Bai, Fang, Ma, Liao, Liu, Zhu, Zhang, Liu, Fang and Wang.)

To understand the biological characteristics of the reemerging pseudorabies virus (PRV) strains, a total of 392 tissue samples were collected from diseased pigs during reemerging PR outbreaks between 2012 and 2019 on farms in central China where swine had been immunized with Bartha-K61 and 51 (13. 01%) were positive for the gE gene by PCR. Sixteen PRV strains were isolated and caused clinical symptoms and death in mice. Subsequently, gE, gC, gB, and gD complete genes were amplified from the 16 PRV isolates and sequenced. Phylogenetic analysis based on these four gene sequences shows that the 16 PRV isolates were more closely related to the Chinese PRV variants (after 2012) but genetically differed from early Chinese PRV isolates (before 2012). Sequence analysis reveals that PRV isolates exhibited amino acid insertions, substitutions, or deletions compared with early Chinese PRV isolates and European-American PRV strains. In addition, this is the first report that eight isolates (8/16) in this study harbor a unique amino acid substitution at position 280 (F to L) of the gC protein, and six isolates have an amino acid substitution at position 338 (A to V) of the gD protein compared with the Chinese PRV variants. The emulsion containing inactivated PRV NY isolate could provide complete protection against the NY isolate. This study might enrich our understanding of the evolution of reemerging PRV strains as well as pave the way for finding a model virus to develop a novel vaccine based on reemerging PRV strains., 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 © 2021 Zheng, Bai, Xu, Zheng, Li, Chen and Wang.)

Background: Recently, the brain-computer interface (BCI) has seen rapid development, which may promote the recovery of motor function in chronic stroke patients., Methods: Twelve stroke patients with severe upper limb and hand motor impairment were enrolled and randomly assigned into two groups: motor imagery (MI)-based BCI training with multimodal feedback (BCI group, n  = 7) and classical motor imagery training (control group, n  = 5). Motor function and electrophysiology were evaluated before and after the intervention. The Fugl-Meyer assessment-upper extremity (FMA-UE) is the primary outcome measure. Secondary outcome measures include an increase in wrist active extension or surface electromyography (the amplitude and cocontraction of extensor carpi radialis during movement), the action research arm test (ARAT), the motor status scale (MSS), and Barthel index (BI). Time-frequency analysis and power spectral analysis were used to reflect the electroencephalogram (EEG) change before and after the intervention., Results: Compared with the baseline, the FMA-UE score increased significantly in the BCI group ( p  = 0.006). MSS scores improved significantly in both groups, while ARAT did not improve significantly. In addition, before the intervention, all patients could not actively extend their wrists or just had muscle contractions. After the intervention, four patients regained the ability to extend their paretic wrists (two in each group). The amplitude and area under the curve of extensor carpi radialis improved to some extent, but there was no statistical significance between the groups., Conclusion: MI-based BCI combined with sensory and visual feedback might improve severe upper limb and hand impairment in chronic stroke patients, showing the potential for application in rehabilitation medicine., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Yi-Qian Hu et al.)

Three new metal-organic frameworks (MOFs), {(CH 3 NH 3 ) 3 [Ba 2 (TTHA)(NO 3 )(H 2 O) 2 ]}·2H 2 O ( 1 ), {(CH 3 NH 3 ) 4 [Ba 3 (HTTHA) 2 (H 2 O) 7 ]}·3H 2 O ( 2 ), and [Ba 7 (TTHA) 2 (NO 3 ) 2 (H 2 O) 10 ]·2H 2 O ( 3 ) (H 6 TTHA = 1,3,5-triazine-2,4,6-triamineh-exaacetic acid) have been synthesized and characterized. The sensing properties of 1 - 3 were explored with regard to volatile organic compounds (VOCs) by the quartz crystal microbalance (QCM) technique. The results indicated that 1 and 2 have a much higher selectivity and response to chloromethanes (CH 2 Cl 2 , CHCl 3 , and CCl 4 ) compared with H 2 O, CH 3 OH, CH 3 CH 2 OH, CH 3 CN, (CH 3 ) 2 CO, C 6 H 6 , C 6 H 5 CH 3 , C 6 H 5 CH 2 CH 3 , and C 6 H 5 Cl at room temperature. Furthermore, 1 and 2 sensing film also exhibits excellent reversibility and stability, and the response and recovery times are almost within 10 s. 3 displays a lower response and poor selectivity to the above VOCs. The significant difference may be caused by their different structural characteristics. The Ba 2+ ions are all decacoordinated in 1 and 2 , while Ba 2+ ions have more open metal sites in 3 . So, the high selectivity and response of 1 and 2 may be due to the exchange of coordination water molecules with chloromethanes and possible electrostatic effects between (CH 3 NH 3 ) + cations and chloromethanes containing more electronegative Cl atoms. DFT calculation results show that the bond energy of Ba-Cl and Ba-O is not much different, so chloromethanes at high concentrations may exchange coordination water to form weak Ba···Cl interactions and show higher response values. 3 has no obvious VOCs selectivity and higher response due to more open sites of Ba 2+ ions and smaller pore size. This work develops a fast and effective method to detect chloromethanes, providing a new opportunity for designing QCM gas sensors coated with different MOF materials.