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Ming-Yue Zhu,* Rong Li,* Jie Xu, Fei She, Xin Du, Wei Zhang Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang, Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100048, People’s Republic of China, Tel +86 010-66867373, Email zhangw8642@126.comObjective: To clarify variations of diagnosis and treatment in the emergency care of critically ill patients not infected with novel coronavirus (COVID-19) prior to and amidst the COVID-19 pandemic.Methods: A retrospective cohort study was conducted to compare and analyze the diagnosis and treatment data of critically ill patients with non-COVID-19 infection who were admitted to the emergency department of the Fourth Medical Center of Chinese PLA General Hospital from January 2019 to November 2022. The variations in emergency care of the pandemic were summarized, and the influence of the pandemic on emergency care was assessed.Results: A total of 6634 critically ill patients with non-COVID-19 infection were included in this study. These patients were elderly, high incidence of chronic diseases, and extended emergency duration during the pandemic. Notably, the proportion of patients requiring intensive care was twofold higher compared to the period before the pandemic. Throughout the pandemic, patients experienced prolonged emergency durations, increased overall costs and daily expenses per patient. Further investigation revealed that elderly patients exhibited worse medical conditions, requiring lengthier emergency treatment and incurring escalated healthcare expenses. However, the presence of pre-existing chronic diseases did not appear to influence disease severity, nor extended emergency durations or heightened healthcare expenditures. Irrespective of the pandemic phase—be it short-term, medium-term, or long-term emergency care—greater healthcare spending was necessary.Conclusion: There was no difference in the disease spectrum of emergency critical ill patients with non-COVID-19 infection prior to and amidst the COVID-19 pandemic, nor the duration and expenditure in prior chronic illness patients. However, the disease severity and emergency duration have led to an increase in the total cost and economic intensity of emergency care for all patients during the epidemic. Especially, elderly patients required longer emergency duration, greater healthcare spending, and more inpatient medical resources than usual.Keywords: novel coronavirus epidemic, emergency, elderly

Meng-yuan Zhu,1–3,* Wen-jian Liu,1,2,* Hua Wang,1,2,* Wei-da Wang,1,2 Na-wei Liu,1,2 Yue Lu1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Hematological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 3Department of Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China*These authors contributed equally to this workBackground/aims: Diffuse large B-cell lymphoma (DLBCL) is a highly common type of malignant and heterogeneous non-Hodgkin’s lymphoma. Tumor-associated macrophages, specially the M2-type, promote tumor progression and drug resistance. The clinical outcome of patients with high neuron-specific enolase (NSE) expression is worse than that with low NSE expression. The tumor-promoting mechanism of NSE, however, remains unclear. This study explored the role of NSE in macrophage polarization associated with the immune microenvironment of DLBCL.Results: Our results showed that NSE protein expression was higher in lymphoma cell lines than in the B lymphocytes. Functional studies demonstrated that upregulation of NSE in lymphoma cells could promote M2 polarization and migration ability of macrophage, thereby consequently promoting the progression of lymphoma in vitro and in vivo. Further mechanism studies revealed that lymphoma-derived exosomes could mediate NSE into macrophages, NSE enhanced nuclear p50 translocation with subsequent defective classical nuclear factor-κB activity in macrophages.Conclusions: These results indicate that NSE may be a potential target for lymphoma therapy and a prognosis marker for lymphoma.Keywords: neuron-specific enolase, diffuse large B-cell lymphoma, macrophage

Mengye Zhu,1,* Fuqing Zhou,2,* Lingchao Li,1 Qin Yin,3 Mizhen Qiu,1 Yong Zhang1 1Department of Pain Clinic, 2Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 3Department of Pain Clinic, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Spinal cord injury (SCI) complicated by epidural anesthesia, though rare, can result in neuropathic pain. However, the treatment for this kind of life-altering injury remains a challenge. A 7-year-old girl was referred with dyskinesia and severe pain in her right lower extremity due to an accidental SCI following lumbar puncture. After treatment with analgesics such as gabapentin, mecobalamin, and dexamethasone/methylprednisolone for 1 week, the myodynamia had improved, but progressive pain persisted. After treatment with neurotropin, a gradual decrease in visual analog scale score from 7 to 0 was observed. We herein first describe that neurotropin produced sustained relief of pain induced by SCI. This case suggests that neurotropin might be a promising drug in treating pediatric neuropathic pain caused by SCI. Keywords: spinal cord injury, pain, neurotropin, children

Junzhao Chen,1,* Chenxi Yan,1,* Mengyu Zhu,1,* Qinke Yao,1 Chunyi Shao,1 Wenjuan Lu,1 Jing Wang,2 Xiumei Mo,2 Ping Gu,1 Yao Fu,1 Xianqun Fan1 1Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 2Biomaterials and Tissue Engineering Laboratory, College of Chemistry and Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Cornea transplant technology has progressed markedly in recent decades, allowing surgeons to replace diseased corneal endothelium by a thin lamellar structure. A thin, transparent, biocompatible, tissue-engineered substratum with corneal endothelial cells for endothelial keratoplasty is currently of interest. Electrospinning a nanofibrous structure can simulate the extracellular matrix and have beneficial effects for cell culture. Silk fibroin (SF) has good biocompatibility but poor mechanical properties, while poly(L-lactic acid-co-Ɛ-caprolactone) (P(LLA-CL)) has good mechanical properties but poor biocompatibility. Blending SF with P(LLA-CL) can maintain the advantages of both these materials and overcome their disadvantages. Blended electrospun nanofibrous membranes may be suitable for regeneration of the corneal endothelium. The aim of this study was to produce a tissue-engineered construct suitable for endothelial keratoplasty.Methods: Five scaffolds containing different SF:P(LLA-CL) blended ratios (100:0, 75:25, 50:50, 25:75, 0:100) were manufactured. A human corneal endothelial (B4G12) cell line was cultured on the membranes. Light transmission, speed of cell adherence, cell viability (live-dead test), cell proliferation (Ki-67, BrdU staining), and cell monolayer formation were detected on membranes with the different blended ratios, and expression of some functional genes was also detected by real-time polymerase chain reaction.Results: Different blended ratios of scaffolds had different light transmittance properties. The 25:75 blended ratio membrane had the best transmittance among these scaffolds. All electrospun nanofibrous membranes showed improved speed of cell adherence when compared with the control group, especially when the P(LLA-CL) ratio increased. The 25:75 blended ratio membranes also had the highest cell proliferation. B4G12 cells could form a monolayer on all scaffolds, and most functional genes were also stably expressed on all scaffolds. Only two genes showed changes in expression.Conclusion: All blended ratios of SF:P(LLA-CL) scaffolds were evaluated and showed good biocompatibility for cell adherence and monolayer formation. Among them, the 25:75 blended ratio SF:P(LLA-CL) scaffold had the best transmittance and the highest cell proliferation. These attributes further the potential application of the SF:P(LLA-CL) scaffold for corneal endothelial transplantation. Keywords: silk fibroin, poly(L-lactic acid-co-Ɛ-caprolactone), B4G12, corneal endothelium, regeneration

Lavender essential oil (LEO) has been shown to relieve pain in humans, but the underlying neural mechanisms remain unknown. Here, we found that inhalation exposure to 0.1% LEO confers antinociceptive effects in mice with complete Freund adjuvant (CFA)-induced inflammatory pain through activation of projections from the anterior piriform cortex (aPir) to the insular cortex (IC). Specifically, in vivo fiber photometry recordings and viral tracing data show that glutamatergic projections from the aPir (aPir Glu ) innervate GABAergic neurons in the IC (IC GABA ) to inhibit local glutamatergic neurons (IC Glu ) that are hyperactivated in inflammatory pain. Optogenetic or chemogenetic activation of this aPir Glu →IC GABA→Glu pathway can recapitulate the antinociceptive effects of LEO inhalation in CFA mice. Conversely, artificial inhibition of IC-projecting aPir Glu neurons abolishes LEO-induced antinociception. Our study thus depicts an LEO-responsive olfactory system circuit mechanism for alleviating inflammatory pain via aPir→IC neural connections, providing evidence to support development of aroma-based treatments for alleviating pain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

Materials and their interfaces are the core for the development of a large variety of fields, including catalysis, energy storage and conversion. In this case, tip-enhanced Raman spectroscopy (TERS), which combines scanning probe microscopy with plasmon-enhanced Raman spectroscopy, is a powerful technique that can simultaneously obtain the morphological information and chemical fingerprint of target samples at nanometer spatial resolution. It is an ideal tool for the nanoscale chemical characterization of materials and interfaces, correlating their structures with chemical performances. In this review, we begin with a brief introduction to the nanoscale characterization of materials and interfaces, followed by a detailed discussion on the recent theoretical understanding and technical improvements of TERS, including the origin of enhancement, TERS instruments, TERS tips and the application of algorithms in TERS. Subsequently, we list the key experimental issues that need to be addressed to conduct successful TERS measurements. Next, we focus on the recent progress of TERS in the study of various materials, especially the novel low-dimensional materials, and the progresses of TERS in studying different interfaces, including both solid-gas and solid-liquid interfaces. Finally, we provide an outlook on the future developments of TERS in the study of materials and interfaces.

The central auditory system encompasses two primary functions: identification and localization. Spatial release from masking (SRM) highlights speech recognition in competing noise and improves the listening experience when a spatial cue is introduced between noise and target speech. This assessment focuses on the integrity of auditory function and holds clinical significance. However, infants or pre-lingual subjects sometimes provide less reliable results. This study investigates the value of cortical auditory evoked potentials (CAEPs) onset and acoustic change complex (ACC) as an objective measurement of SRM. Thirty normal-hearing young adults (11 males) were recruited. We found the spatial separation of signals and noise (±90° symmetrically) resulted in a signal-to-noise ratio (SNR) improvement of 9.00 ± 1.71 dB behaviorally. It significantly enhanced cortical processing at all SNR levels, shortened CAEP latencies, and increased amplitudes, resulting in a greater number of measurable peaks for ACC. SRM showed mild to moderate correlations with the differences between two conditions in CAEP measures. The regression model combining N1'-P2' amplitude at 5 dB SNR ( R 2 = 0.26), P1 amplitude at 0 dB SNR ( R 2 = 0.14), and P1 latency at -5 dB SNR ( R 2 = 0.15), explained 45.3% of the variance in SRM. Our study demonstrates that introducing spatial cues can improve speech perception and enhance central auditory processing in normal-hearing young adults. CAEPs may contribute to predictions about SRM and hold potential for practical application. NEW & NOTEWORTHY The neural encoding of spatial release from masking (SRM) can be observed in normal-hearing young adults. Spatial separation between target and masker improves speech perception in noise and enhances central auditory processing. The behavioral results showed mild-to-moderate correlations with electrophysiological measures, with acoustic change complex (ACC) amplitude being a better indicator than onset components. Cortical auditory evoked potentials (CAEPs) may contribute to predictions about spatial release from masking, especially when behavioral tests are less reliable.

Most coexisting insect species exhibit stunted growth compared to the single species on plants. This phenomenon reflects an interspecific antagonism that draws extensive attention while the underlying mechanisms remain largely unknown. Mirids (Apolygus lucorum) and cotton bollworms (Helicoverpa armigera) are two common pests in cotton fields. We identified a secretory protein, ASP1, from the oral secretion of mirids, which was found in the nucleus of mirid-infested cotton leaves. ASP1 specifically targets the transcriptional corepressor TOPLESS (TPL) and inhibits NINJA-mediated recruitment of TPL, thereby promoting plant defense response and gossypol accumulation in cotton glands. ASP1-enhanced defense inhibits the growth of cotton bollworms on cotton plants, while having little impact on mirids. The mesophyll-feeding characteristic allows mirids to avoid most cotton glands, thereby invalidating cotton defense. Our investigation reveals the molecular mechanism by which mirids employ cotton defense to selectively inhibit the feeding of cotton bollworms., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Persistent hyperactivity of nociceptors is known to contribute significantly to long-lasting sensitization and ongoing pain in many clinical conditions. It is often assumed that nociceptor hyperactivity is mainly driven by continuing stimulation from inflammatory mediators. We have tested an additional possibility: that persistent increases in excitability promoting hyperactivity can be induced by a prototypical cellular signaling pathway long known to induce late-phase long-term potentiation (LTP) of synapses in brain regions involved in memory formation. This cAMP-PKA-CREB-gene transcription-protein synthesis pathway was tested using whole-cell current clamp methods on small dissociated sensory neurons (primarily nociceptors) from dorsal root ganglia (DRGs) excised from previously uninjured ("naïve") male rats. Six-hour treatment with the specific Gαs-coupled 5-HT4 receptor agonist, prucalopride, or with the adenylyl cyclase activator forskolin induced long-term hyperexcitability (LTH) in DRG neurons that manifested 12-24 h later as action potential (AP) discharge (ongoing activity, OA) during artificial depolarization to -45 mV, a membrane potential that is normally subthreshold for AP generation. Prucalopride treatment also induced significant long-lasting depolarization of resting membrane potential (from -69 to -66 mV), enhanced depolarizing spontaneous fluctuations (DSFs) of membrane potential, and produced trends for reduced AP threshold and rheobase. LTH was prevented by co-treatment of prucalopride with inhibitors of PKA, CREB, gene transcription, or protein synthesis. As in the induction of synaptic memory, many other cellular signals are likely to be involved. However, the discovery that this prototypical memory induction pathway can induce nociceptor LTH, along with reports that cAMP signaling and CREB activity in DRGs can induce hyperalgesic priming, suggest that early, temporary, cAMP-induced transcriptional and translational mechanisms can induce nociceptor LTH that might last for long periods. The present results also raise the question of whether reactivation of primed signaling mechanisms by re-exposure to inflammatory mediators linked to cAMP synthesis during subsequent challenges to bodily integrity can "reconsolidate" nociceptor memory, extending the duration of persistent hyperexcitability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Recently, unconventional antiferromagnets that enable the spin splitting (SS) of electronic states have been theoretically proposed and experimentally realized, where the magnetic sublattices containing moments pointing at different directions are connected by a novel set of symmetries. Such SS is substantial, k-dependent, and independent of the spin-orbit coupling (SOC) strength, making these magnets promising materials for antiferromagnetic spintronics. Here, combined with angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT) calculations, a systematic study on CrSb, a metallic spin-split antiferromagnet candidate with Néel temperature T N = 703 K, is conducted. The data reveal the electronic structure of CrSb along both out-of-plane and in-plane momentum directions, rendering an anisotropic k-dependent SS that agrees well with the calculational results. The magnitude of such SS reaches up to at least 0.8 eV at non-high-symmetry momentum points, which is significantly higher than the largest known SOC-induced SS. This compound expands the choice of materials in the field of antiferromagnetic spintronics and is likely to stimulate subsequent investigations of high-efficiency spintronic devices that are functional at room temperature., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Color-tunable room temperature phosphorescence (RTP) materials possess potential applications in multicolor imaging, multichannel anticounterfeiting, and information encryption. Herein, we synthesized two zero-dimensional cadmium-organic halides, (H-aepy) 2 CdX 4 (referred to as CdX-aepy ; X = Cl - , Br - ; aepy = 3-(2-aminoethyl)pyridine), both of which exhibit long-lived excitation wavelength- and time-dependent RTP. Experimental and theoretical results suggest that the multicolor RTP can be ascribed to the coemission of pristine H-aepy ligands and halogen-affected H-aepys, supporting that suitably introducing halogens can be an efficient strategy for constructing multicolor RTP materials. Additionally, we also demonstrate that the two phosphors can be applied in multichannel anticounterfeiting and information encryption. This work reports two hybrids with color-tunable RTP, as well as provides new insight into the effect of halogens on the regulation of RTP.

Aim: To assess the research capacity of 3014 clinical nurses in northeastern China, examining their participation in research and self-assessed competencies to advance nursing practice., Background: Nursing research is essential for the development of the nursing discipline, yet significant progress in enhancing the research capabilities of nursing staff has been limited over the past decades. Clinical nurses, central to the execution of research activities, need improved research skills to identify relevant topics and synthesise clinical experiences with the literature., Design: A cross-sectional survey., Methods: In 2023, using a convenience sampling method, a cross-sectional questionnaire survey was conducted on 3014 nurses in a Grade A tertiary hospital. The questionnaire included questions on basic information and scientific research, as well as a self-evaluation scale assessing the nurses' capability for conducting scientific research., Results: Among the nurses participating in the survey, 29.66% (894) had published academic papers in Chinese, 2.06% (62) had published papers in Science Citation Index journals, 2.39% (72) had hosted nursing research projects, 5.87% (177) had participated in nursing research projects and 71% (2140) expressed their willingness to participate in nursing research activities. The average score on the self-evaluation of research capability was 54.08 ± 24.55, with scores ranging from 0 to 120., Conclusion: The clinical nurses' research capacity scores are at the midpoint of the scale (0-120), indicating basic research capabilities with room for improvement. There is a high willingness to engage in research. Nursing managers should consider these factors in training programmes and promote research activities to improve the team's scientific capability., Relevance to Clinical Practice: This study reveals a critical gap between nurses' willingness and actual involvement in research, emphasising the need for enhanced research skills to improve nursing practice., Patient or Public Contribution: This study did not require patient or public involvement in its design, outcome measures or execution. The contribution of patients/members of the public was limited solely to data collection., (© 2024 John Wiley & Sons Ltd.)

Myeloid-derived growth factor (MYDGF) is a cytokine that exhibits a variety of biological functions. This study focused on utilizing BL21(DE3) strain engineering and fermentation strategies to achieve high-level expression of soluble human MYDGF (hMYDGF) in Escherichia coli. Initially, the E. coli expressing strain BL21(DE3) was engineered by deleting the IpxM gene and inserting the GROEL/S and Trigger factor genes. The engineered E. coli strain BL21(TG)/pT-MYDGF accumulated 3557.3 ± 185.6 μg/g and 45.7 ± 6.7 mg/L of soluble hMYDGF in shake flask fermentation, representing a 15.6-fold increase compared to the control strain BL21(DE3)/pT-MYDGF. Furthermore, the yield of hMYDGF was significantly enhanced by optimizing the fermentation conditions. Under optimized conditions, the 5L bioreactor yielded up to 2665.8 ± 164.3 μg/g and 407.6 ± 42.9 mg/L of soluble hMYDGF. The results indicate that the implementation of these optimization strategies could enhance the ratio and yield of soluble proteins expressed by E.coli, thereby meeting the demands of industrial production. This study employed sophisticated strategies to lay a solid foundation for the industrial application of hMYDGF., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain., Methods: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms., Results: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors., Conclusion: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Egg production traits are crucial in the poultry industry, including age at first egg (AFE), egg number (EN) at different stages, and laying rate (LR). Ducks exhibit higher egg production capacity than other poultry species, but the genetic mechanisms are still poorly understood. In this study, we collected egg-laying data of 618 Peking ducks from 22 to 66 weeks of age and genotyped them by whole-genome resequencing. Genetic parameters were calculated based on SNPs, and a genome-wide association study (GWAS) was performed for these traits. The SNP-based heritability of egg production traits ranged from 0.09 to 0.54. The GWAS identified nine significant SNP loci associated with AFE and egg number from 22 to 66 weeks. These loci showed that the corresponding alleles were positively correlated with a decrease in the traits. Moreover, three potential candidate genes (ENSAPLG00020011445, ENSAPLG00020012564, TMEM260) were identified. Functional enrichment analyses suggest that specific immune responses may have a critical impact on egg production capacity by influencing ovarian function and oocyte maturation processes. In conclusion, this study deepens the understanding of egg-laying genetics in Peking duck and provides a sound theoretical basis for future genetic improvement and genomic selection strategies in poultry.

Objective: To explore the risk factors for progression to chronic kidney disease (CKD) in patients with cardiac valve replacement surgery-associated acute kidney injury (AKI). Methods: A retrospective, nested case-control study was conducted at Fuwai Central China Cardiovascular Hospital. The study subjects were patients who underwent cardiac valve replacement surgery from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min -1 ·(1.73 m 2 ) -1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint event. The baseline clinical data were compared between the two groups. The measurement data with non-normal distribution was represented as M ( Q 1 , Q 3 ). Logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic (ROC) curve was drawn to evaluate the performance for predicting CKD in cardiac valve replacement surgery-associated AKI patients. Results: A total of 149 cardiac valve replacement surgery-associated AKI patients (86 males and 63 females) were included in the study, aged (59.0±10.2) years. There were 27 patients (18.1%) who progressed to new-onset CKD 90 days after the occurrence of cardiac valve replacement surgery-associated AKI. Compared with non-CKD group, patients in CKD group had older age [66 (58, 70) vs 59 (53, 64) years], lower baseline eGFR [76.3 (65.8, 98.5) vs 92.7 (78.5, 101.6) ml·min -1 ·(1.73 m 2 ) -1 ], higher proportion of preoperative hypertension [51.9% (14/27) vs 27.9% (34/122)] and serum creatinine at discharge [136 (101, 165) vs 86 (65, 104) μmol/L], and the differences were statistically significant (all P <0.05). The multivariate logistic regression analysis results revealed that older age ( OR =1.063, 95% CI : 1.001-1.129, P =0.047), preoperative hypertension ( OR =3.070, 95% CI : 1.105-8.532, P =0.031) and higher serum creatinine at discharge ( OR =1.026, 95% CI :1.013-1.038, P <0.001) were risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI. The clinical risk model including age, preoperative hypertension, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting progression to CKD in patients with cardiac valve replacement surgery-associated AKI [the area under the curve (AUC)=0.865, 95% CI: 0.790-0.940, P <0.001]. Conclusion: Older age, preoperative hypertension and higher serum creatinine at discharge are risk factors for progression to CKD in patients with cardiac valve replacement surgery-associated AKI.

Background: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy., Objective: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI., Design, Setting, Participants and Interventions: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules., Main Outcome Measures: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m 2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria., Results: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m 2 in the YQPY group and 5.78 mL/min per 1.73 m 2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m 2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively., Conclusion: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285., (Copyright © 2024. Published by Elsevier B.V.)

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials., Competing Interests: Competing interests statement:The authors declare no competing interest.

Coordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non-toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H 2 O 2 ) production through two electron oxygen reduction (2e-ORR) is a challenge on Mn-centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)-coordinated active environment with reactant enrichment effect on boundary-rich porous carbon-based electrocatalysts, which facilitates the selective and rapid synthesis of H 2 O 2 through 2e-ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H 2 O 2 productivity up to 15.1 mol g cat -1  h -1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn-based electrocatalyst in H 2 O 2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high-curvature boundaries facilitate oxygen (O 2 ) adsorption and result in local O 2 enrichment due to the enhanced interaction between carbon surface and O 2 . These merits together ensure the efficient formation of H 2 O 2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity., (© 2024 Wiley-VCH GmbH.)

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Pain involves neuroimmune crosstalk, but the mechanisms of this remain unclear. Here we showed that the splenic T helper 2 (T H 2) immune cell response is differentially regulated in male mice with acute versus chronic neuropathic pain and that acetylcholinergic neurons in the dorsal motor nucleus of the vagus (ACh DMV ) directly innervate the spleen. Combined in vivo recording and immune cell profiling revealed the following two distinct circuits involved in pain-mediated peripheral T H 2 immune response: glutamatergic neurons in the primary somatosensory cortex (Glu S1HL )→ACh DMV →spleen circuit and GABAergic neurons in the central nucleus of the amygdala (GABA CeA )→ACh DMV →spleen circuit. The acute pain condition elicits increased excitation from Glu S1HL neurons to spleen-projecting ACh DMV neurons and increased the proportion of splenic T H 2 immune cells. The chronic pain condition increased inhibition from GABA CeA neurons to spleen-projecting ACh DMV neurons and decreased splenic T H 2 immune cells. Our study thus demonstrates how the brain encodes pain-state-specific immune responses in the spleen., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system., Methods: Extracted proteins from 34 cerebrospinal fluid (CSF) samples [patients with MOGAD (MOG group, n = 12); healthy controls (HC group, n = 12); patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases (IND group, n = 10)] were processed and subjected to label-free quantitative proteomics. Supervised partial least squares-discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) models were also performed based on proteomics data. Functional analysis of differentially expressed proteins (DEPs) was performed using Gene Ontology, InterPro, and Kyoto Encyclopedia Genes and Genomes. An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD., Results: Four hundred and twenty-nine DEPs (149 upregulated and 280 downregulated proteins) were identified in the MOG group compared to the HC group according to the P value and fold change (FC). Using the O-PLS-DA model, 872 differentially abundant proteins were identified with variable importance projection (VIP) scores > 1. Five proteins (gamma-glutamyl hydrolase, cathepsin F, interalpha-trypsin inhibitor heavy chain 5, latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1) overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired. Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades, cell adhesion, axon guidance, and glycosphingolipid biosynthesis compared to the HC group., Conclusion: The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates., (© 2022. The Author(s).)

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated 1-3 . Recent attention on a set of previously overlooked symmetry operations in magnetic materials 4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets 5-10 . Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe 2 ), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

To explore the distribution characteristics, blooming risk mechanism and driving factors of phytoplankton community structure in Fuchunjiang Reservoir. The variation characteristics of phytoplankton, zooplankton and physicochemical indicators in Fuchunjiang Reservoir and its upper and lower reaches were investigated in 2020 and 2021. Based on the phytoplankton functional groups, non-metric multidimensional scale analysis, redundancy analysis and other statistical methods, the seasonal succession characteristics and driving factors of phytoplankton functional groups were analyzed. A total of 18 phytoplankton functional groups were identified, in of which 10 were predominant. The composition of phytoplankton functional groups in the Fuchunjiang Reservoir was significant different. Spatially, the upstream were dominated by group C and P while the represent species were Cyclotella and Aulacoseira ,reflecting the mixed meso-eutrophic environments. However, group P was the main group in Fuchunjiang reservoir, and the dominance decreased gradually along the stream direction. Meanwhile, in the downstream, MP has an absolute advantage at Qiantang River estuary. It reflected the environmental characteristics of frequent disturbance and high turbidity of tide-sensing rivers. In addition, the predominant functional groups demonstrated strong seasonal variations. The dominant functional groups were diverse in summer and consisted of P+L0+J+M+S1+H1+MP. In addition to group P ( Aulacoseira ), which was dominant throughout the year, it also included several groups represented by cyanobacteria and chlorophyta, reflecting the environmental characteristics of changeable habitats and vigorous productivity. In autumn, the succession was dominated by H1 group represented by Dolichospermum and the representative function groups were P and H1, reflecting the hydrological background of reduced flow and static flow. In winter, the increase of Cyclotella led to the predominance of group C, which was dominated by P+C, reflecting the changing conditions of weakened water exchange and intensified eutrophication problems. In spring, the dominant functional groups were gradually enriched and were composed of C, D, P, and MP, which also reflected the changing environmental habitat characteristics which caused by increasing rainfall and air temperature. According to the results of the C-R-S growth strategy, the Fuchunjiang Reservoir has been in the R strategy for a long time, which was consistent with the habitat characteristics of Fuchunjiang Reservoir and its upper and lower reaches with high disturbance and low stress. In addition, C strategy and S strategy appeared in some reaches, reflecting the variability of water quality and hydrology. RDA analysis showed that water temperature, discharge, zooplankton biomass, permanganate index, total nitrogen and total phosphorus were significantly correlated with the seasonal succession of phytoplankton functional groups ( P &lt; 0.05), and temperature and flow pattern were probably the most critical factors for the succession. Studies have shown that the impact of hydrometeorological processes on phytoplankton in the Fuchunjiang Reservoir is crucial:high temperature and changing discharge during the summer may lead to cyanobacterial blooms in the Fuchunjiang reservoir; To reduce the risk of algal blooms, it is still necessary to increase the control of nitrogen and phosphorus load in rivers, and fully consider the coordination of water conservancy dispatch methods.

Introduction: Hu sheep, known for its high quality and productivity, lack fundamental scientific research in China., Methods: This study focused on the effects of 24 h postmortem aging on the meat physiological and transcriptomic alteration in Hu sheep., Results: The results showed that the 24 h aging process exerts a substantial influence on the mutton color, texture, and water content as compared to untreated group. Transcriptomic analysis identified 1,668 differentially expressed genes. Functional enrichment analysis highlighted the importance of glycolysis metabolism, protein processing in endoplasmic reticulum, and the FcγR-mediated phagocytosis pathway in mediating meat quality modification following postmortem aging. Furthermore, protein-protein interaction analysis uncovered complex regulatory networks involving glycolysis, the MAPK signaling pathway, protein metabolism, and the immune response., Discussion: Collectively, these findings offer valuable insights into the molecular mechanisms underlying meat quality changes during postmortem aging in Hu sheep, emphasizing the potential for improving quality control strategies in mutton production., 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 Li, Feng, Xia, Chen, Lu, Wei, Qian, Zhu, Gao, Meng, You, Tian, Liang, Li, Lv, Rui, Wei and Zhang.)

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC 50  = 2.68 ± 0.27 μM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3β, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.

Dying tumor cells release biological signals that exhibit antigenicity, activate cytotoxic T lymphocytes, and induce immunogenic cell death (ICD), playing a key role in immune surveillance. We demonstrate that the flavonoid LW-213 activates endoplasmic reticulum stress (ERS) in different tumor cells and that the lysosomal calcium channel TRPML1 mediates the ERS process in human cellular lymphoma Hut-102 cells. Apoptotic tumor cells induced by ERS often possess immunogenicity. Tumor cells treated with LW-213 exhibit damage-associated molecular patterns (DAMPs), including calreticulin translocation to the plasma membrane and extracellular release of ATP and HMGB1. When co-cultured with antigen-presenting cells (APCs), LW-213-treated tumor cells activated APCs. Two groups of C57BL/6J mice were inoculated with Lewis cells: a "vaccine group", which demonstrated that LW-213-treated tumor cells promote the maturation of dendritic cells and increase CD8 + T cells infiltration in the tumor microenvironment and a "pharmacodynamic group", treated with a combination of LW-213 and PD1/PD-L1 inhibitor (BMS-1), which reduced tumor growth and significantly prolonged the survival time of mice in the "pharmacodynamic group". Therefore, LW-213 can be developed as a novel ICD inducer, providing a new concept for antitumor immunotherapy., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC., Methods: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes., Results: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity., Conclusions: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC., (© 2023. The Author(s).)

Background: Accumulating evidences have demonstrated that overwhelming inflammation occurs in the process of Coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVM). No specific therapy is available. More than an effective Janus-associated kinase (JAK) inhibiter, ruxolitinib exerts a critical role in the inflammatory diseases. In this study, we investigated the potential effect of ruxolitinib on CVB3-induced acute viral myocarditis., Method: In vivo, BALB/c mice were intraperitoneally injected of CVB3, treated of a successive gavage of ruxolitinib for seven days, and subjected to a series of analysis. In vitro, primary bone marrow-derived macrophages (BMDMs) and cardiac fibroblasts were isolated, cultured, treated, harvested and finally detected., Results: In vivo, acute viral myocarditis was successfully induced by the injection of CVB3 characterized by impaired cardiac function, predominant infiltration of inflammatory cells, necroptosis of myocardium, great increase of cardiac troponin I (cTnI) and cytokine levels, replication of CVB3, and excessive activation of JAK-STAT pathways. Oral administration of ruxolitinib suppressed the activation of JAK-STAT pathway in a dosage-dependent way, lessened the infiltration of inflammatory cells and necroptosis of myocardium, reduced the levels of cTnI and cytokines, and finally alleviated CVB3-induced cardiac dysfunction, with the reduced production of type I interferon and no promising effect on the replication of CVB3. In vitro, the treatment of ruxolitinib inhibited the activation of JAK-STAT pathway and increase of multiple cytokines mRNA levels in BMDMs and had no protective effect against CVB3 replication in cardiac fibroblasts., Conclusions: Our study suggested that ruxolitinib ameliorated CVB3-induced AVM by inhibiting the activation of JAK-STAT pathway, infiltration of inflammatory cells and necroptosis of myocardium, which may provide a novel strategy for AVM therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Denitrification is a major process in aquatic ecosystems, and it competes with cyanobacterial growth for nitrogen. However, the effect of denitrification on cyanobacterial blooms under the background of climate change remains unclear. This study explored the interaction between lake denitrification and formation of cyanobacterial blooms, using the historical water quality monitoring data of North Lake Taihu over five years from 2017 to 2021 and via incubation experiments of cyanobacteria and sediment denitrification. The monitoring data showed that algal biomass (Chla as a proxy) primarily peaked during summer and autumn. The seasonal variations in total N concentration showed a completely opposite trend than that of algal biomass, which peaked in winter and spring. Nitrate was the major component of dissolved inorganic nitrogen, and the nitrate concentration was approximately zero in summer and autumn. The total phosphorus concentration varied in the same way as the Chla concentration. The experimental results showed that Cyanobacteria did not grow when the temperature was below 20℃. In comparison, denitrification showed a significant linear relationship with temperatures between 10-25℃ ( R 2 =0.99) and reached the maximum value of (62.98±21.36) μmol·(kg·h) -1 in Lake Taihu at 25℃. Additionally, the nitrate concentration threshold at the maximum denitrification rate was 4 mg·L -1 . Cyanobacteria assimilate nitrate for growth, thereby reducing the concentration of nitrate required for denitrification. This study indicated that the advance in lake temperature warming due to climate change may result in earlier growth of cyanobacteria, thereby leading to large amounts of N being assimilated by algae before denitrification, further affecting the dynamics of cyanobacterial blooms. The present results are scientifically important for explaining the mechanism of cyanobacterial bloom rebound in Lake Taihu under the background of recent climate changes.

Phytophthora cactorum is one of the most economically important soilborne oomycete pathogens in the world. It infects more than 200 plant species spanning 54 families, most of which are herbaceous and woody species. Although traditionally considered to be a generalist, marked differences of P. cactorum isolates occur in degree of pathogenicity to different hosts. As the impact of crop loss caused by this species has increased recently, there has been a tremendous increase in the development of new tools, resources, and management strategies to study and combat this devastating pathogen. This review aims to integrate recent molecular biology analyses of P. cactorum with the current knowledge of the cellular and genetic basis of its growth, development, and host infection. The goal is to provide a framework for further studies of P. cactorum by highlighting important biological and molecular features, shedding light on the functions of pathogenicity factors, and developing effective control measures., Taxonomy: P. cactorum (Leb. & Cohn) Schröeter: kingdom Chromista; phylum Oomycota; class Oomycetes; order Peronosporales; family Peronosporaceae; genus Phytophthora., Host Range: Infects about 200 plant species in 154 genera representing 54 families. Economically important host plants include strawberry, apple, pear, Panax spp., and walnut., Disease Symptoms: The soilborne pathogen often causes root, stem, collar, crown, and fruit rots, as well as foliar infection, stem canker, and seedling damping off., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Psychological and physical stressors have been implicated in gastric disorders in humans. The mechanism coupling the brain to the stomach underlying stress-induced gastric dysfunction has remained elusive. Here, we show that the stomach directly receives acetylcholinergic inputs from the dorsal motor nucleus of the vagus (ACh DMV ), which are innervated by serotonergic neurons in the dorsal raphe nucleus (5-HT DRN ). Microendoscopic calcium imaging and multi-tetrode electrophysiological recordings reveal that the 5-HT DRN  → ACh DMV  → stomach circuit is inhibited with chronic stress accompanied by hypoactivate gastric function. Artificial activation of this circuit reverses the gastric dysfunction induced by chronic stress in both male and female mice. Our study demonstrates that this 5-HT DRN  → ACh DMV  → stomach axis drives gastric dysfunction associated with stress, thus providing insights into the circuit basis for brain regulation of the stomach., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To evaluate the symptom experience of patients with benign prostatic hyperplasia and bladder fistula. Exploring the mediating effect of self-efficacy on the relationship between symptom experience and quality of life in patients with benign prostatic hyperplasia undergoing long-term indwelling cystostomy., Methods: This study used a cross-sectional survey design. Patients with prostatic hyperplasia with cystostomy in the Urology department of General Hospital of Eastern Theater Command from January 2020 to February 2023 were selected, and relevant data were collected by IPSS, IIEF-5, HAMD, GSES, and quality of life score scale for statistical analysis. We then construct a structural equation model to evaluate the mediating effect of self-efficacy between symptom experience and quality of life., Results: The average score of IPSS was (22.55±8.26) ; the average score of IIEF-5 was (10.54±4.10) ; the average score of HAMD was (6.82±2.35) ; the average score of self-efficacy was (20.80±8.65) ; and the average score of quality of life was (71.65±12.55) . Symptom experience was significantly negatively correlated with self-efficacy and quality of life( r=－0.496 , P<0.01；r=－0.518 , P<0.01) . Self-efficacy was significantly positively correlated with quality of life( r= 0.412，P<0.05). Symptom experience significantly negatively affected quality of life through self-efficacy (Effect = －0.218，P = 0.014) ., Conclusion: Self-efficacy is positively correlated with the quality of life of patients with benign prostatic hyperplasia who have long-term indwelling cystostomy tube. Nursing staff can improve the level of self-efficacy of patients by implementing corresponding interventions.

Parkinson's disease(PD)is the second most common neurodegenerative disease after Alzheimer's disease,with high morbidity and high disability rate.Since the early symptoms of PD are not typical and often similar to those of normal aging or other diseases.It is easy to missed diagnosis and misdiagnosis,which seriously affects the diagnosis and treatment of this disease and aggravetes the burden on the patients' life.MicroRNAs(miRNA)are a class of endogenous non-coding RNAs that are involved in post-transcriptional regulation by binding to target messenger RNAs(mRNA).They are highly conserved,short,easy to obtain,and can stably exist in peripheral body fluids.They have been used as biomarkers for a variety of diseases.Recent studies have demonstrated that miRNA play an important role in the development of PD.This paper reviews the recent research progress of miR-7/124/155,three mature miRNA in PD,aiming to provide reference for clarifying the pathogenesis and guiding the diagnosis and treatment of PD.

Background: Heart failure (HF) often affects the progress of sepsis patients, although its impact on outcomes is inconsistent and inconclusive., Aim: To conduct a systematic review and meta-analysis of the impact of HF on mortality in patients with sepsis., Methods: PubMed, Embase, Web of Science, and the Cochrane Library databases were searched to compare the outcomes of sepsis patients with HF. A random effect model was used to summarize the mortality data, and the odds ratio (OR) and 95% confidence interval (CI) were calculated as effect indicators., Results: Among 18001 records retrieved in the literature search, 35712 patients from 10 separate studies were included. The results showed that sepsis patients with HF were associated with increased total mortality (OR = 1.80, 95%CI: 1.34-2.43; I 2 = 92.1%), with high heterogeneity between studies. Significant subgroup differences according to age, geographical location, and HF patient sample were observed. HF did not increase the 1-year mortality of patients (OR = 1.11, 95%CI: 0.75-1.62; I 2 = 93.2%), and the mortality of patients with isolated right ventricular dysfunction (OR=2.32, 95%CI: 1.29-4.14; I 2 = 91.5%) increased significantly., Conclusion: In patients with sepsis, HF is often associated with adverse outcomes and mortality. Our results call for more high-quality research and strategies to improve outcomes for sepsis patients with HF., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Early and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM)., Methods: In our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data., Results: Ten viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired., Discussion: Our result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns., 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, Guo, Zhu, Mao, Xu, Hua, Xu, Jiang, Zhao, Zhang, Sheng, Jiang, Yuan and Gao.)

Background: Antisense transcript of the B-cell translocation gene 3 (ASBEL) is a highly conserved antisense non-coding RNA (ncRNA) and participates in a variety of biological processes. However, the ASBEL expression status in pancreatic ductal adenocarcinoma (PDAC) and its correlation with BTG3 expression and tumor cell progression were not completely clear., Objective: We conducted cell experiments and animal experiments to confirm that ASBEL plays a crucial role in the tumorigenesis of PDAC by targeting BTG3., Methods: ASBEL regulation in PDAC tumorigenesis was evaluated using Western blotting, quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry, and cell transfection. We also evaluated the expression of ASBEL and BTG3 in tumor tissues and cells using Western blotting and quantitative real-time polymerase chain reaction. Finally, we explored the role of ASBEL in tumor development by silencing or overexpressing ASBEL gene in AsPC-1 or CFPAC-1 cells, respectively, and evaluated the antitumor activity in vivo using an ASBEL antagonist., Results: Our study revealed the expression of ASBEL in all pancreatic cell lines. The expression level of ASBEL in tumor tissues was found to be higher than that of paracarcinomatous tissues. ASBEL suppresses expression of BTG3 , enhances proliferation and suppresses apoptosis, and promotes migration and invasion in pancreatic cancer cell. Antagonist regulates the expression of ASBEL in AsPC-1, and suppresses tumor growth in xenograft mouse model., Conclusions: Our results indicate that ASBEL may play a tumor-promoting factor in PDAC by targeting BTG3 and could be as an important biomarker for PDAC treatment. ( Curr Ther Res Clin Exp . 2023; 84:XXX-XXX)., Competing Interests: The authors have indicated that they have no conflicts of interest regarding the content of this article., (© 2023 The Author(s).)

Objective: Breast cancer-related lymphedema (BCRL) is a common post-operative complication in patients with breast cancer. Here, we sought to develop and validate a predictive model of BCRL in Chinese patients with breast cancer., Methods: Clinical and demographic data on patients with breast cancer were collected between 2016 and 2021 at a Cancer Hospital in China. A nomogram for predicting the risk of lymphedema in postoperative patients with breast cancer was constructed and verified using R 3.5.2 software. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics, and the model was internally validated., Results: A total of 1732 postoperative patients with breast cancer, comprising 1212 and 520 patients in the development and validation groups, respectively, were included. Of these 438 (25.39%) developed lymphedema. Significant predictors identified in the predictive model were time since breast cancer surgery, level of lymph node dissection, number of lymph nodes dissected, radiotherapy, and postoperative body mass index. At the 31.9% optimal cut-off the model had AUC values of 0.728 and 0.710 in the development and validation groups, respectively. Calibration plots showed a good match between predicted and observed rates. In decision curve analysis, the net benefit of the model was better between threshold probabilities of 10%-80%., Conclusion: The model has good discrimination and accuracy for lymphedema risk assessment, which can provide a reference for individualized clinical prediction of the risk of BCRL. Multicenter prospective trials are required to verify the predictive value of the model., Competing Interests: Declaration of competing interest All authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIr SST -Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIr SST -Re tri-synaptic circuit in mediating the innate fear response., (© 2022. The Author(s).)

Summary Statement: The present study examined expression of DNA damage markers in VMAT2 Lo PD model mice. The results demonstrate there is a significant increase in these DNA damage markers mostly in the brain regions of 18- and 23-month-old model mice, indicating oxidative stress-induced DNA lesion is an important pathologic feature of this mouse model.

Aims: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and heart failure. However, the effective therapy for DCM is still lacking. Polysulfide contains chains of sulfur atoms, and accumulative evidence has shown that it actively participates in mammalian physiology or pathophysiology. Nevertheless, the potential effects and mechanisms of polysulfide in DCM need further investigation. In the present study, Na 2 S 4 , a polysulfide donor, was employed to investigate the therapeutic effects of polysulfide in DCM. Results: Our results showed that Na 2 S 4 protected cardiomyocytes against high glucose (HG)-induced cardiomyocyte injury. The pathological changes in DCM including cell death, oxidative stress, mitochondrial dysfunction and cardiac hypertrophy were improved by Na 2 S 4 treatment. The left ventricular contractile function in streptozotocin (STZ)-induced diabetic mice was significantly improved by Na 2 S 4 . Mechanistically, Na 2 S 4 upregulated and sulfhydrated peroxisome proliferator-activated receptor-γ (PPARγ) and sirtuin 3 (SIRT-3) in cardiomyocytes. Suppression of PPARγ or SIRT-3 with their specific inhibitors or blockade of sulfhydration abolished the protective effects of Na 2 S 4 . Moreover, mutations of PPARγ or SIRT-3 at specific cysteines diminished the benefits of Na 2 S 4 in HG-challenged cardiomyocytes. Innovation and Conclusion: We demonstrated that Na 2 S 4 prevented the development of DCM via sulfhydration of both PPARγ and SIRT-3. Our results imply that polysulfide may be a potential and promising agent to treat DCM. Antioxid. Redox Signal. 38, 1-17.

Background: Vincosamide (Vinco) was first identified in the methanolic extract of the leaves of Psychotria leiocarpa , and Vinco has important anti-inflammatory effects and activity against cholinesterase, Vinco also has a trait to anti-tumor. However, whether Vinco can inhibit the malignant behaviors of hepatocellular carcinoma (HCC) cells is still unclear. In the present study, we explored the role of Vinco in suppressing the malignant behaviors of HCC cells., Methods: MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide), trypan blue exclusion assay, the Cell Counting Kit (CCK)-8 and flow cytometric analysis were applied to detect the proliferation and apoptosis of HCC cells; electron microscopy was performed to observe the change of cellular mitochondrial morphology; scratch repair and Transwell assays were used to analyze the migration and invasion of HCC cells; expression and localization of proteins were detected by laser confocal microscopy and Western blotting; the growth of the cancer cells in vivo was assessed in a mouse tumorous model., Results: At a dose of 10 - 80 µg/mL, Vinco inhibited the proliferation, migration, invasion and promoted apoptosis of HCC cells in a dose-dependent manner but had low cytotoxicity effect on normal liver cells. Additionally, 80 µg/mL of Vinco could significantly disrupt the morphology of mitochondria, suppress the migration and invasion of HCC cells. The growth of HCC cells in the animal tumorous model was significantly inhibited after treatment with Vinco (10 mg/kg/day) for 3 days. The results of the present study indicated that Vinco (10 - 80 µg/mL) played a role in activating caspase-3, promoting the expression of phosphate and tension homology deleted on chromosome 10 (PTEN), and inhibiting the phosphorylation of AKT (Ser473) and mTOR (Thr2448); Vinco also has a trait for suppressing the expression of CXCR4, Src, MMP9, EpCAM, Ras, Oct4 and cancer stem cell "stemness markers" CD133 and CD44 in HCC cells., Conclusions: Vinco has a role in inhibiting the malignant behaviors of HCC cells; the role molecular mechanism of Vinco may be involved in restraining expression of the growth-, metastasis-related factors, such as Src, Ras, MMP9, EpCAM, CXCR4; activating the activity of caspase-3 and blocking PI3K/AKT signaling pathway. Thus, Vinco should be considered as a new chemotherapy agent for HCC patients., Competing Interests: All the authors confirm that no conflicts of interest are associated with the content of this article., (Copyright 2022, Zhu et al.)

Octacosanol (Oct), a kind of long-chain fatty alcohol extracted from rice bran was applied to study its effects on alleviating ulcerative colitis (UC). Oct was orally administered at 10 mg/kg (Oct-L) and 30 mg/kg (Oct-H) to dextran sulfate sodium (DSS)-induced mice. Here, we reported that oral administration of 30 mg/kg Oct can significantly prevent the weight loss, colon shortening, and decrease the disease activity index (DAI) score. Oct-H supplementation modified the intestinal flora by lowering the Firmicutes/Bacteroidetes (F/B) ratio, increasing the abundance of Prevotellaceae, S24-7, Turicibacter, and meanwhile decreasing Enterococcus and Stenotrophomonas. Based on the PICRUSt2 analysis, Oct-H may exert effects by anti-inflammation and xenobiotics degradation. Furthermore, short-chain fatty acids (SCFAs) levels were raised and the integrity of the gut barrier was protected. In conclusion, Oct-H can relieve clinical symptoms, modulate the gut bacteria and protect the intestinal barrier in UC mice, suggesting the potential of Oct as a food supplementation in alleviating UC. PRACTICAL APPLICATIONS: Ulcerative colitis (UC) is a hard-to-cure disease, with increasing morbidity in recent years. Therefore, finding out a food supplement to alleviate UC is very meaningful. In this work, we showed that octacosanol significantly alleviated ulcerative colitis in mice. We revealed, for the first time, octacosanol's effects on protecting the integrity of the gut barrier, modulating the intestinal flora and its metabolism (SCFAs). Therefore, octacosanol was expected to prevent colitis in an all-round way. Our research might also lay the theoretical foundation for the further development of related functional foods., (© 2022 Wiley Periodicals LLC.)

Objective: To assess the clinical application value of preoperative emotional management combined with family members' interactive description nursing (PEM+FMID) in plasmakinetic enucleation of the prostate (PKEP)., Methods: This perspective study included 108 cases of PKEP performed in our hospital from July 2020 to May 2022. We randomly divided the patients into a control (n = 54) and an observation group (n = 54), the former receiving routine nursing, while the latter PEM+FMID in addition, before surgery. We recorded the operation time, perioperative blood loss and postoperative hospital stay, obtained the patients' Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) scores before and after nursing intervention, and their compliance, satisfaction and postoperative complications after intervention, and compared the data between the two groups., Results: The average postoperative hospital stay was significantly shorter in the observation than in the control group (［6.35 ± 1.39］ d vs ［7.19 ± 1.39］ d, P< 0.05). Compared with the baseline, the SDS and SAS scores of the patients were significantly decreased at 1 week after operation (P < 0.05), and markedly lower in the observation group than in the control (P < 0.05). The compliance rate (87.04% vs 66.67%) and satisfaction rate (92.59% vs 70.37%) of the patients were significantly higher in the observation than in the control group (both P < 0.05), while the total incidence rate of postoperative complications was lower in the former than in the latter (7.41% vs 33.33%, P < 0.05), particularly those of bladder irritation, hematuria, urinary retention and fever (all P < 0.05)., Conclusion: Preoperative emotional management combined with family members' interactive description nursing can effectively relieve the negative emotions of the patients undergoing PKEP, improve their compliance and satisfaction, and reduce postoperative complications.