Search

Context: Ulcerative colitis (UC) is an intractable inflammatory bowel disease that threatens the health of patients. The limited availability of therapeutic strategies makes it imperative to explore more efficient and safer drugs. Indigo naturalis (IN) is a traditional Chinese medicine that possesses many pharmacological activities, including anti-inflammatory, antioxidant, and immunomodulatory activities. The treatment potential of IN for UC has been proven by numerous preclinical and clinical studies in recent years., Objective: This article provides a comprehensive review of the utility and potential of IN in the treatment of UC., Methods: 'Indigo naturalis' 'Qing dai' 'Qingdai' 'Ulcerative colitis' and 'UC' are used as the keywords, and the relevant literature is collected from online databases (Elsevier, PubMed, and Web of Science)., Results and Conclusion: Indirubin, indigo, isatin, tryptanthrin, and β-sitosterol are considered the key components in the treatment of UC with IN. Both preclinical and clinical studies support the efficacy of IN for UC, especially in severe UC or in those who do not respond to or have poor efficacy with existing therapies. The mechanisms of IN for UC are associated with the aryl hydrocarbon receptor pathway activation, immune regulation, oxidative stress inhibition, and intestinal microbial modulation. However, the clinical use of IN has the risks of adverse events such as pulmonary hypertension, which suggests the necessity for its rational application. As a potential therapeutic agent for UC that is currently receiving more attention, the clinical value of IN has been initially demonstrated and warrants further evaluation.

In this study, we investigated the role of total glycosides of Cistanche deserticola (TC) in MPTP-induced neuronal injury. Further, we screened potential inhibitory components of monoamine oxidase B (MAO-B). The study results indicate that TC may improve movement disorders and apoptosis of dopamine (DA) neurons by inhibiting MAO-B activity while reducing the number of glial cells, adjusting the metabolism level of monoamine neurotransmitters, and lowering inflammation and oxidative stress levels. Subsequently, a rapid screening method for drug-containing brain tissue was further constructed, and five candidate components that can cross the blood-brain barrier and bind to MAO-B were screened and submitted for biological activity evaluation and inhibition mechanism research. In summary, we discovered 2'-acetylacteoside as a promising and reversible mixed natural MAO-B inhibitor in TC and developed a rapid screening method for screening central nervous system drugs with blood-brain barrier permeability characteristics, providing potential candidates and an effective screening strategy for neurodegenerative diseases.

Background: Sepsis-induced myocardial dysfunction (SIMD) may contribute to the poor prognosis of septic patients. Carvacrol (2-methyl-5-isopropyl phenol), a phenolic monoterpene compound extracted from various aromatic plants and fragrance essential oils, has multiple beneficial effects such as antibacterial, anti-inflammatory, and antioxidant properties. These attributes make it potentially useful for treating many diseases. This study aims to investigate the effects of CAR on LPS-induced myocardial dysfunction and explore the underlying mechanism., Results: H9c2 cells were stimulated with 10 µg/ml LPS for 12 h, and c57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to establish a septic-myocardial injury model. Our results showed that CAR could improve cardiac function, significantly reduce serum levels of inflammatory cytokines (including TNF-α, IL-1β, and IL-6), decrease oxidative stress, and inhibit cardiomyocyte apoptosis in LPS-injured mice. Additionally, CAR significantly downregulated the expression of TLR4, MyD88, and NF-κB in LPS-injured mice and H9c2 cells. It also inhibited the upregulation of inflammasome components (such as NLRP3, GSDMD, and IL-1β) in H9c2 cells triggered by LPS., Conclusion: Taken together, CAR exhibited potential cardioprotective effects against sepsis, which may be mainly attributed to the TLR4/MyD88/NF-κB pathway and the NLRP3 inflammasome., Competing Interests: Declarations Ethics approval and consent to participate All the animal experiments procedures were performed with the approval of the Air Force Military Medical University (No. 20191206). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

An ingenious microstructure of electromagnetic microwave absorption materials is crucial to achieve strong absorption and a broad bandwidth. Herein, one-dimensional (1D) carbon fibers with implantation of zero-dimensional (0D) ZIF-8-derived carbon frameworks and construction of a three-dimensional (3D) microcosmic multichannel porous structure are fabricated by electro-blown spinning, solvent-thermal reaction, and high-temperature pyrolysis techniques. The 1D carbon fiber skeleton with a multichannel structure provides a direct axial conductive pathway for charge transport, which plays an important role in dielectric loss. The 0D surface carbon frameworks offer plenty of heterogeneous interfaces to trigger intensive interfacial polarization loss and act as dihedral angles for microwave scattering. The 3D microcosmic multichannel pores can not only generate multiple reflections as much as possible to dissipate electromagnetic microwave energy but also supply huge interior cavities to improve impedance matching. Thanks to the synergistic effect of a strong electrically conductive pathway for enhancing the conductive loss, a plenteous heterogeneous interface for triggering intensive interfacial polarization loss, microcosmic multichannel pores for generating multiple reflections and improving impedance matching, and N and O atom doping for inducing dipole polarization, the optimal sample with an ingenious microstructure delivers an excellent absorption performance of a minimum reflection loss of -35.5 dB at a thickness of 5.0 mm and an effective absorption bandwidth of 6.72 GHz (10.96-17.68 GHz) at a thickness of 2.0 mm. Such a well-designed multichannel porous carbon fiber may pave the way for the exploitation of high-performance microwave absorbing materials.

Aims: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies., Methods: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy., Results: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays., Conclusions: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Hydrogen sulfide (H 2 S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H 2 S alleviates skeletal muscle ageing by regulating autophagy has not been reported., Methods: Mice were administered 150 mg/kg/day of D-galactose (D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H 2 S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot., Results: NaHS was found to effectively restore the H 2 S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the β-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1., Conclusions: H 2 S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Objective: Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD)., Methods: The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis., Results: T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P =0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance., Conclusions: T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD., 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 Yao, Li, Wang, Liu, Zheng, Zhong, Ma, Yang, Sun, He, Huang and Wang.)

Background: Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be effectively treated by traditional Chinese medicine (TCM). Qingfei Huatan, a TCM formula, has been reported to effectively alleviate the clinical symptoms of COPD patients. However, there is a lack of multi-centre, randomised, double-blind, controlled clinical trials documenting the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD (AECOPD)., Objective: This study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD, thereby providing high-quality clinical evidence., Design, Setting, Participants and Interventions: A total of 276 patients with AECOPD were included in this multi-centre, randomised, double-blind, placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:1. Patients in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day, for 14 days, in addition to Western medicine treatment. All patients were followed up for 3 months., Main Outcome Measures: The primary outcome was time taken to symptom stabilisation. The secondary outcomes included duration of antibiotic use, clinical symptom and sign score, TCM syndrome score, dyspnoea score, and quality of life (QOL) score. Meanwhile, the safety of the formula was assessed through routine urine and stool tests, electrocardiograms, liver and kidney function tests, and the observation of adverse events throughout the trial., Results: The time taken for effective stabilisation (P < 0.05) and obvious stabilisation (P < 0.01), and the duration of antibiotic use (P < 0.05) were significantly shorter in the treatment group than in the control group. On days 6, 9, 12 and 14 of treatment, clinical symptom and sign score decreased in both groups, particularly in the treatment group (P < 0.01). On days 9, 12 and 14 of treatment, the TCM syndrome scores of both groups were reduced (P < 0.01), with more significant reductions in the treatment group. At 3 months after the end of treatment, the treatment group continued to have lower clinical symptom and sign score and TCM syndrome score than the control group (P < 0.01). On days 6, 9, 12 and 14 of treatment, dyspnoea and QOL scores were markedly reduced in the two groups (P < 0.05 and P < 0.01, respectively), especially in the treatment group. At 3 months after the end of treatment, dyspnoea and QOL scores were lower in the treatment group than those in the control group (P < 0.01). No serious adverse events were observed in either group., Conclusion: The Qingfei Huatan formula can effectively shorten the duration of AECOPD and antibiotic use, significantly relieve clinical symptoms, and increase QOL for AECOPD patients, with a favourable safety profile. These results suggest that this formula can be used as a complementary treatment for AECOPD patients., Trial Registration: The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1900026576). Please cite this article as: Zhu HZ, Li CY, Liu LJ, Tong JB, Lan ZH, Tian SG, Li Q, Tong XL, Wu JF, Zhu ZG, Li SY, Li JS. Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial. J Integr Med. 2024; 22(5): 561-569., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Background: This study investigates the efficacy and safety of bridging intravenous thrombolysis (IVT) before endovascular therapy (EVT) compared with EVT alone in patients with large infarction core., Methods: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library from January 2015 to June 2024. Included studies involved patients with acute ischemic stroke with an Alberta Stroke Program Early CT Score of ≤5 or an ischemic core volume of ≥50 mL. Studies were required to provide either 90-day modified Rankin Scale (mRS) score, reperfusion, symptomatic intracranial hemorrhage (sICH), or 90-day mortality., Results: Nine observational studies with 2641 patients were analyzed. The IVT+EVT group had a higher rate of 90-day functional independence (mRS 0-2; OR 1.56, 95% CI 1.31 to 1.87; adjusted OR (aOR) 1.43, 95% CI 1.21 to 1.68) and 90-day functional outcome (mRS 0-3; OR 1.34, 95% CI 1.11 to 1.62; aOR 1.18, 95% CI 1.02 to 1.37) compared with EVT alone. There was no significant difference in successful reperfusion (OR 1.01, 95% CI 0.62 to 1.64; aOR 1.07, 95% CI 0.74 to 1.54) and 90-day mortality (OR 0.86, 95% CI 0.73 to 1.02; aOR 0.89, 95% CI 0.77 to 1.04) between the two groups. Moreover, patients who received IVT+EVT had a higher rate of sICH (OR 1.30, 95% CI 1.03 to 1.64; aOR 2.21, 95% CI 1.22 to 4.01)., Conclusions: In patients with large infarction core, bridging IVT before EVT is associated with favorable functional outcomes compared with EVT, even though bridging therapy entails a higher risk of sICH. Further trials are needed to confirm these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce proteotoxic stress. Phosphatase and tensin homolog (PTEN) have been reported to be involved in proteostasis, and PTEN-associated pathways are commonly altered in CCA. Celastrol, a triterpene from plants, exhibits cytotoxic effects in various types of cancer. However, the underlying mechanisms remain unclear., Purpose: We investigated the therapeutic effect of celastrol in CCA and identified the molecular characteristics of tumors that were sensitive to celastrol. The target of celastrol was explored. We then evaluated the candidate combination therapeutic strategy to increase the effectiveness of celastrol in celastrol-insensitive CCA tumors., Methods: Various CCA cells were categorized as either celastrol-sensitive or celastrol-insensitive based on their response to celastrol. The molecular characteristics of cells from different groups were determined by RNA-seq. PTEN status and its role in proteasome activity in CCA cells were investigated. The CMAP analysis, molecular docking, and functional assay were performed to explore the effect of celastrol on proteasome activities. The correlation between PTEN status and clinical outcomes, as well as proteasomal activity, were measured in CCA patients. The synergistic therapeutic effect of autophagy inhibitors on celastrol-insensitive CCA cells were measured., Results: Diverse responses to celastrol were observed in CCA cells. PTEN expression varied among different CCA cells, and its status could impact cell sensitivity to celastrol: PTEN high tumor cells were resistant to celastrol, while PTEN low cells were more sensitive. Celastrol induced proteasomal dysregulation in CCA cells by directly targeting PSMB5. Cells with low PTEN status transcriptionally promoted proteasome subunit expression in an AKT-dependent manner, making these cells more reliant on proteasomal activities to maintain proteostasis. This caused the PTEN low CCA cells sensitive to celastrol. A negative correlation was found between PTEN levels and the proteasome signature in CCA patients. Moreover, celastrol treatment could induce autophagy in PTEN high CCA cells. Disrupting the autophagic pathway in PTEN high CCA cells enhanced the cytotoxic effect of celastrol., Conclusion: PTEN status in CCA cells determines their sensitivity to celastrol, and autophagy inhibitors could enhance the anti-tumor effect in PTEN high CCA., 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 © 2024 Elsevier GmbH. All rights reserved.)

This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥ 70 and another with IQ < 70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥ 70, with both VAI and NVI showing statistically significant differences (all P < 0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P < 0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥ 70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Paragonimiasis is a typical food-borne zoonotic disease. Hosts acquire Paragonimus infection through the ingestion of raw or undercooked crayfish and crab. The clinical manifestations of the disease are varied, and it is often misdiagnosed or missed. The diagnosis of paragonimiasis should be considered comprehensively. Praziquantel is the first choice for treatment, and albendazole can be used in combination with repeated courses in severe cases., Case Summary: We report a case of liver paragonimiasis that was misdiagnosed as an abscess. The patient presented with fatigue and poor appetite for 2 months, and was diagnosed with liver abscess in the local hospital. After 6 months, the patient visited our hospital because of recurrent abdominal pain and was diagnosed with liver paragonimiasis based on epidemiological history, clinical presentations, and laboratory findings. He was treated with praziquantel (25 mg/kg) three times a day for 3 days; however, the symptoms still presented after treatment. He was treated with oral praziquantel and albendazole for one further course. Follow-up suggested that the treatment was effective and the symptoms improved., Conclusion: The combination of albendazole and praziquantel may improve the therapeutic efficacy of paragonimiasis., Competing Interests: Conflict-of-interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

As a complementary and alternative therapy, acupuncture is widely used in the prevention and treatment of various diseases. However, the understanding of the mechanism of acupuncture effects is still limited due to the lack of systematic biological validation. Notably, proteomics technologies in the field of acupuncture are rapidly evolving, and these advances are greatly contributing to the research of acupuncture. In this study, we review the progress of proteomics research in analyzing the molecular mechanisms of acupuncture for neurological disorders, pain, circulatory disorders, digestive disorders, and other diseases, with an in-depth discussion around acupoint prescription and acupuncture manipulation modalities. The study found that proteomics has great potential in understanding the mechanisms of acupuncture. This study will help explore the mechanisms of acupuncture from a proteomic perspective and provide information to support future clinical decisions., 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 Author(s).)

Myocardial infarction (MI) is one of the leading causes of heart failure with highly complicated pathogeneses. miR-654-3p has been recognized as a pivotal regulator of controlling cell survival. However, the function of miR-654-3p in cardiomyocytes and MI has yet to be reported. This study aimed to identify the role of miR-654-3p in the regulation of myocardial infarction. To understand the contribution of miR-654-3p on heart function, we generated cardiac-specific knockdown and overexpression mice using AAV9 technology in MI injury. Mechanically, we combined cellular and molecular techniques, pharmaceutical treatment, RNA sequencing, and functional testing to elucidate the potential pathological mechanisms. We identified that mice subjected to MI decreased the expression of miR-654-3p in the border and infarcted area. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. Furthermore, we found a deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death but not other programmed cell death. Intriguingly, miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Cardiac elevating miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Using RNA sequence and molecular biological approaches, we found overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function. Our finding identified the character of miR-654-3p in protecting against MI damage by mediating pyroptosis and mitochondrial metabolism. These findings provide a new mechanism for miR-654-3p involvement in the pathogenesis of MI and reveal novel therapeutic targets. miR-654-3p expression was decreased after MI. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. The deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death. miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Overexpression of miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function., (© 2024. The Author(s).)

The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA 1 . As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities 2 . Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions 3,4 . Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel β-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this., Objective: To assess the efficacy of VMMC in preventing incident HIV infection among MSM., Design: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436)., Setting: 8 cities in China., Participants: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months., Intervention: VMMC., Measurements: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis., Results: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P  = 0.029), and the HIV incidence was lower in the intervention group (log-rank P  = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation., Limitation: Few HIV seroconversions and limited follow-up period., Conclusion: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines., Primary Funding Source: The National Science and Technology Major Project of China., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3317.

Background: Serum carbohydrate antigen 50 (CA50) is an auxiliary diagnostic marker for various solid tumors, but it remains unclear whether CA50 in pleural fluid can assist in the diagnosis of malignant pleural effusion (MPE). This study aimed to evaluate the diagnostic accuracy of pleural fluid CA50 for MPE in pleural effusion patients with undetermined causes., Methods: This study prospectively recruited pleural effusion patients with undetermined causes who visited the Affiliated Hospital of Inner Mongolia Medical University between September 2018 and July 2021. We measured pleural fluid CA50 level with an electrochemiluminescence assay. We analyzed the diagnostic accuracy of CA50 and carcinoembryonic antigen (CEA) for MPE with the receiver operating characteristic (ROC) curve. The net benefits of CA50 and CEA were analyzed using the decision curve analysis (DCA)., Results: We enrolled 66 MPEs and 87 benign pleural effusions (BPEs). MPE patients had significantly higher CA50 and CEA than BPE patients. The area under the ROC curve (AUC) of CA50 was 0.72 (95% CI: 0.63-0.80). CA50 had a sensitivity of 0.30 (95% CI: 0.19-0.41) and a specificity of 1.00 (95% CI: 1.00-1.00) at the threshold of 15 IU/mL. The decision curve of CA50 was above the reference line at the calculated risk probability of between 0.30 and 1.00. Venn diagram indicated that some patients with low CEA (<50 or <150 ng/mL) and/or negative cytology can be identified by positive CA50 (>15 IU/mL)., Conclusions: Pleural fluid CA50 has moderate accuracy and net benefit for detecting MPE. CA50 >15 IU/mL can be used to diagnose MPE. The combination of CA50 and CEA improves the diagnostic sensitivity for MPE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-68/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Deqi is an important prerequisite for acupuncture to achieve optimal efficacy. Chinese medicine has long been concerned with the relationship between Deqi and the clinical efficacy of acupuncture. However, the underlying mechanisms of Deqi are complex and there is a lack of systematic summaries of objective quantitative studies of Deqi . Acupuncture Deqi can achieve the purpose of treating diseases by regulating the interaction of local and neighboring acupoints, brain centers, and target organs. At local and neighboring acupoints, Deqi can change their tissue structure, temperature, blood perfusion, energy metabolism, and electrophysiological indicators. At the central brain level, Deqi can activate the brain regions of the thalamus, parahippocampal gyrus, postcentral gyrus, insular, middle temporal gyrus, cingulate gyrus, etc. It also has extensive effects on the limbic-paralimbic-neocortical-network and default mode network. The brain mechanisms of Deqi vary depending on the acupuncture techniques and points chosen. In addition, Deqi 's mechanism of action involves correcting abnormalities in target organs. The mechanisms of acupuncture Deqi are multi-targeted and multi-layered. The biological mechanisms of Deqi are closely related to brain centers. This study will help to explore the mechanism of Deqi from a local-central-target-organ perspective and provide information for future clinical decision-making., 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 Zhong, Yao, Liu, Wang, He, Sun, Huang, Ma, Zheng, Li, Zhang, Cong and Wang.)

Background: Colorectal cancer is the second-leading cause of cancer deaths in the United States. Fecal immunochemical tests (FITs) are a primary means of colorectal cancer screening at some health care institutions because of scheduling backlogs for screening, diagnostic, and surveillance endoscopies. However, delays in mail delivery can impact timely analysis of samples, possibly leading to false-negative results and the need for repeat tests. Some patients might be unwilling to submit another test when informed that an earlier sample cannot be reliably analyzed, resulting in a missed opportunity for screening., Observations: The Jesse Brown Veterans Affairs Medical Center has experienced some success through contacting the local US Postal Service (USPS) to avoid these delays; however, the problem often unpredictably recurs with USPS staff turnover. Laboratories and health systems experiencing delays should first ensure that prepaid envelopes have the correct postage and that their USPS accounts are properly funded, to confirm that insufficient funds are not contributing to the delayed deliveries. Adding additional language to the preprinted envelopes, such as "time-sensitive," may also be helpful. Asking patients to drop off test kits at the laboratory or using private letter carriers is not feasible in some communities. Other strategies include establishing a drop-off box at clinic offices or considering other screening methods, such as colonoscopies or flexible sigmoidoscopies., Conclusions: Clinicians who work in health care systems that use FIT kits need to be aware of the impact that local USPS delays can have on the reliability of FIT results. Health systems should be prepared to implement mitigation strategies if significant delays with mail delivery are encountered., Competing Interests: Author disclosures: The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2024 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Objective: Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases., Methods: We collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis., Results: Regarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group ( p  < 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of Clostridiales, Clostridia, Firmicutes, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, Actinobacteria, Veillonellaceae, Longum, Copri, Megamonas and Callidus than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the Lachnospiraceae in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group., Conclusion: The disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases., 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 Chen, Zeng, Cai, Gu and Yang.)

Background: The primary risk of HIV transmission in China has shifted from injecting drug use (IDU) to sexual contact since 2006. We evaluated the prevalence trends of HIV, hepatitis C virus (HCV), syphilis, and sexual and drug use behaviors among drug users. Methods: People who use drugs participated in any of four rounds of cross-sectional surveys during 2010-2017 in Chongqing. Participants were tested for HIV, HCV, and syphilis. Questionnaire interviewing was conducted to collect behavioral information. Chi-square and trend tests were employed to assess the changes in diseases and behaviors over time. Results: A total of 8,171 people who inject drugs (PWID) and 5,495 non-injection drug users (NIDU) were included in the analyses. HIV prevalence among PWID in four rounds of the survey in 2010-11, 2012-13, 2014-15, and 2016-17 was 11.5%, 9.7%, 6.5%, and 6.9%, and among NIDU, 2.4%, 1.4%, 2.1% and 2.6%, respectively. HCV prevalence among PWID was 83.5%, 85.2%, 67.1% and 79.7% ( P < 0.001), and among NIDU, 22.2%, 10.8%, 13.4% and 14.8%, ( P < 0.001). Conclusions: The declining HIV and HCV prevalence among PWID is coincident with declining risky drug use behaviors. Tailored disease prevention and interventions targeting PWID and NIDU are needed.

Due to the ultrahigh theoretical specific capacity (3860 mAh g -1 ) and low redox potential (-3.04 V vs. standard hydrogen electrode), Lithium (Li) metal anode (LMA) received increasing attentions. However, notorious dendrite and volume expansion during the cycling process seriously hinder the development of high energy density Li metal batteries. Constructing three-dimensional (3D) current collectors for Li can fundamentally solve the intrinsic drawback of hostless for Li. Therefore, this review systematically introduces the design and synthesis engineering and the current development status of different 3D collectors in recent years (the current collectors are divided into two major parts: metal-based current collectors and carbon-based current collectors). In the end, some perspectives of the future promotion for LMA application are also presented., (© 2024 Wiley‐VCH GmbH.)

Using the self-developed fused indium wetting technology and planar waveguide, the uniform heat dissipation of the slab crystal and uniform pumping of the pump light were achieved, respectively. Based on the master oscillator power amplification (MOPA) scheme, the power was then amplified when the seed light source passed through the Nd:YAG slab crystal three times. Additionally, the image transfer system that we added to the amplified optical path achieved high beam quality. Finally, we obtained a rectangular pulsed laser with an output average power of 4461 W, a repetition frequency of 20 kHz, a pulse width of 62 ns, an optical-to-optical conversion efficiency of 26.8%, and a beam quality of β x =7.0 and β y =7.7.

Purpose: Marital status has been reported to influence the survival outcomes of various cancers, but its impact on patients with mantle cell lymphoma (MCL) remains unclear. This study aimed to assess the influence of marital status at diagnosis on overall survival (OS) and cancer-specific survival (CSS) in patients with MCL., Methods: The study utilized data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 databases, including 6437 eligible individuals diagnosed with MCL from 2000 to 2018. A 1:1 propensity matching method (PSM) minimized confounding factor. Univariate and multivariate analyses determined hazard ratios (HR). Stratified hazard models were developed for married and unmarried statuses across time intervals., Results: Married patients exhibited better 5-year OS and CSS rates compared to unmarried patients (54.2% vs. 39.7%, log-rank p < 0.001; 62.6% vs. 49.3%, log-rank p < 0.001). Multivariate analysis indicated that being unmarried was an independent risk factor for OS (adjusted HR 1.420, 95% CI 1.329-1.517) and CSS (adjusted HR 1.388, 95% CI 1.286-1.498). After PSM, being unmarried remained an independent risk factor for both OS and CSS. Among unmarried patients, widowed individuals exhibited the poorest survival outcomes compared to patients with other marital statuses, with 5-year OS and CSS rates of 28.5% and 41.0%, respectively. Furthermore, in the 10-year OS and CSS hazard model for widowed individuals had a significantly higher risk of mortality, with the probability of overall and cancer-specific mortality increased by 1.7-fold and 1.6-fold, respectively., Conclusion: Marital status at diagnosis is an independent prognostic factor for MCL patients, with widowed individuals showing worse OS and CSS than those who are married, single, or divorced/separated. Adequate psychological and social support for widowed patients is crucial for improving outcomes in this patient population., (© 2024. The Author(s).)

Background: Excessive or inappropriate use of social media has been linked to disruptions in regular work, well-being, mental health, and overall reduction of quality of life. However, a limited number of studies documenting the impact of social media on health-related quality of life (HRQoL) are available globally., Aim: This study aimed to explore the perceived social media needs and their impact on the quality of life among the adult population of various selected countries., Methodology: A cross-sectional, quantitative design and analytical study utilized an online survey disseminated from November to December 2021., Results: A total of 6689 respondents from ten countries participated in the study. The largest number of respondents was from Malaysia (23.9%), followed by Bangladesh (15.5%), Georgia (14.8%), and Turkey (12.2%). The prevalence of social media users was over 90% in Austria, Georgia, Myanmar, Nigeria, and the Philippines. The majority of social media users were from the 18-24 age group. Multiple regression analysis showed that higher education level was positively correlated with all four domains of WHOQoL. In addition, the psychological health domain of quality of life was positively associated in all countries. Predictors among Social Media Needs, Affective Needs (β = -0.07), and Social Integrative Needs (β = 0.09) were significantly associated with psychological health., Conclusion: The study illuminates the positive correlation between higher education levels and improved life quality among social media users, highlighting an opportunity for policymakers to craft education-focused initiatives that enhance well-being. The findings call for strategic interventions to safeguard the mental health of the global social media populace, particularly those at educational and health disadvantages., (© 2024. The Author(s).)

Objective: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area., Methods: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts., Results: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449)., Conclusion: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression., 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 © 2024 Elsevier Inc. All rights reserved.)

This is the case of a gravida 3 para 1 woman in her late 20s with underlying haemoglobin constant spring who visited a healthcare clinic for an antenatal check-up. Towards the end of her second trimester, she experienced lethargy. During her antenatal booking, she was diagnosed with mild asymptomatic anaemia, high serum ferritin, T saturation of 88% and abnormal liver function tests. She was referred to a hospital where an MRI scan revealed over 2 g of iron deposits in her liver, leading to a revised diagnosis of iron overload. Treatment included deferoxamine and expectant management throughout her antenatal period, and her delivery was uncomplicated. While iron deficiency anaemia is common in pregnancy, it is crucial not to overlook iron deposition and the distinction from acute fatty liver during pregnancy to prevent treatment delays., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg 2+ -dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.

The poor reversibility and stability of Zn metal anode (ZMA) caused by uncontrolled Zn deposition behaviors and serious side reactions severely impeded the practical application of aqueous Zn metal battery. Herein, a liquid-dynamic and self-adaptive protective layer (LSPL) was constructed on the ZMA surface for inhibiting dendrites and by-products formation. Interestingly, the outer LSPL consists of liquid perfluoropolyether (PFPE), which can dynamically adapt volume change during repeat cycling and inhibit side reactions. Moreover, it can also decrease the de-solvation energy barrier of Zn 2+ by strong interaction between C-F bond and foreign Zn 2+ , improving Zn 2+ transport kinetics. For the LSPL inner region, in-situ formed ZnF 2 through the spontaneous chemical reaction between metallic Zn and part PFPE can establish an unimpeded Zn 2+ migration pathway for accelerating ion transfer, thereby restricting Zn dendrites formation. Consequently, the LSPL-modified ZMA enables reversible Zn deposition/dissolution up to 2000 h at 1 mA cm -2 and high coulombic efficiency of 99.8% at 4 mA cm -2 . Meanwhile, LSPL@Zn||NH 4 V 4 O 10 full cells deliver an ultralong cycling lifespan of 100 00 cycles with 0.0056% per cycle decay rate at 10 A g -1 . This self-adaptive layer provides a new strategy to improve the interface stability for next-generation aqueous Zn battery., (© 2023 Wiley-VCH GmbH.)

In aquatic ecosystems, light penetrating the sediment surface in shallow lakes may regulate the internal phosphorus (P) release through benthic primary production, which subsequently affects oxidation, pH levels, and alkaline phosphatase activity in the upper sediment. To study the effects of light exposure on the P dynamics at the sediment-water interface under eutrophic conditions, a two-month mesocosm experiment was conducted in twelve cement tanks (1000 L each). The tanks were equipped with Light-Emitting Diode (LED) lights, and surface sediments collected from eutrophic Lake Nanhu (China) were exposed to four different light intensities (0, 50, 100, 200 μmol m -2 s -1 ). The results revealed that: 1) Both the total phosphorus concentration and the phosphorus release flux from the sediment were lower in the light treatments (mean value, 0.59-0.71 mg L -1 and 0.00-0.01 mg m -2 d -1 , respectively) than in the control treatment (0.77 mg L -1 and 0.01 mg m -2 d -1 , respectively), indicating that light supplement could decrease the internal P release. 2) Benthic primary production promoted by light directly absorbed soluble reactive phosphorus and decreased the internal P release. The resulting improved production could also increase dissolved oxygen concentrations at the sediment-water interface, thus indirectly inhibiting internal P release. 3) The relative contributions of direct absorption and indirect inhibition on the internal P release ranged between 23% to 69% and 31% to 77% depending on the light intensity., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Single cell modification or hybridization technology has become a popular direction in bioengineering in recent years, with applications in clean energy, environmental stewardship, and sustainable human development. Here, we draw attention to nanoarmor, a representative achievement of cytoprotection and functionalization technology. The fundamental principles of nanoarmor need to be studied with input from multiple disciplines, including biology, chemistry, and material science. In this review, we explain the role of nanoarmor and review progress in its applications. We also discuss three main challenges associated with its development: self-driving ability, heterojunction characteristics, and mineralization formation. Finally, we propose a preliminary classification system for nanoarmor., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The association between human immunodeficiency virus (HIV) status and readmissions and death outcomes in patients with established heart failure (HF) remains unclear. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science up to March 1st, 2023, for cohort studies of adult patients (≥18 years) diagnosed with HF and recorded HIV status at baseline. Our analysis included 7 studies with 10,328 HF patients living with HIV and 48,757 HF patients without HIV. Compared to HF patients without HIV, those with HIV had a higher risk of all-cause deaths (HR: 1.20, 95% CI: 1.15-1.25). HIV infection was also associated with increased risks of HF-associated readmission (HR: 1.34, 95% CI: 1.03-1.75) and all-cause readmission (HR: 1.27, 95% CI: 1.10-1.46). Our study highlights the independent association between HIV and poor HF outcomes, emphasizing the need for improved management in individuals living with HIV., Competing Interests: Declaration of Competing Interest Dr. Neilan has been a consultant to and received fees from Bristol Myers Squibb, Genentech, CRC Oncology, Roche, Sanofi and Parexel Imaging Pharmaceuticals. Dr. Neilan also reports grant funding from Astra Zeneca and Bristol Myers Squibb related to the cardiac effects of immune checkpoint inhibitors, all outside of the current work. Dr. Zanni is Principal Investigator on an investigator-initiated research grant from Gilead to her institution, which is unrelated to this work. Other authors have no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy., Methods: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm., Results: Before treatment, compared with the control group, in the observation group, MoCA score was lower ( P <0.001), CDR score and the levels of FPG and HbA1c were higher ( P< 0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged ( P< 0.05, P< 0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased ( P< 0.05, P< 0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped ( P< 0.001), and that of myo-inositol (MI) to Cr in the right side increased ( P< 0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher ( P< 0.001), the scores of CDR, SAS and HAMD were reduced ( P< 0.01, P< 0.05), the reaction times of Flanker conflict and Stroop conflict shortened ( P< 0.001, P< 0.05), and the accuracy of Flanker conflict and 1-back increased ( P< 0.001, P< 0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased ( P< 0.05), that of MI to Cr in the right decreased ( P< 0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence ( r =0.671, P= 0.012) and this ratio was positively correlated with the reaction time of Stroop conflict ( r= 0.576, P= 0.039)., Conclusions: Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.

Despite being one of the most promising materials in anode materials, molybdenum sulfide (MoS 2 ) encounters certain obstacles, such as inadequate cycle stability, low conductivity, and unsatisfactory charge-discharge (CD) rate performance. In this study, a novel approach is employed to address the drawbacks of MoS 2 . Carbon polymer dots (CPDs) are incorporated to prepare three-dimensional (3D) nanoflower-like spheres of MoS 2 @CPDs through the self-assembly of MoS 2 2D nanosheets, followed by annealing at 700 °C. The CPDs play a main role in the creation of the nanoflower-like spheres and also mitigate the MoS 2 nanosheet limitations. The nanoflower-like spheres minimize volume changes during cycling and improve the rate performance, leading to exceptional rate performance and cycling stability in both Lithium-ion and Sodium-ion batteries (LIBs and SIBs). The optimized MoS 2 @CPDs-2 electrode achieves a superb capacity of 583.4 mA h g -1 at high current density (5 A g -1 ) after 1000 cycles in LIBs, and the capacity remaining of 302.8 mA h g -1 after 500 cycles at 5 A g -1 in SIBs. Additionally, the full cell of LIBs/SIBs exhibits high capacity and good cycling stability, demonstrating its potential for practical application in fast-charging and high-energy storage., (© 2023 Wiley-VCH GmbH.)

Background: Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China., Methods: A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020., Results: Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26&#95;33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA-related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B., Conclusion: We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials., (© 2023. The Author(s).)

The dendrite growth and parasitic reactions that occur on Zn metal anode (ZMA)/electrolyte interface hinder the development of aqueous zinc ion batteries (AZIBs) in next-generation renewable energy storage systems. Fortunately, reconstructing the inner Helmholtz layer (IHL) by introducing an electrolyte additive, is viewed as one of the most promising strategies to harvest the stable ZMA. Herein, (4-chloro-3-nitrophenyl) (pyridin-4-yl) methanone (CNPM) with quadruple functional groups is introduced into the ZnSO 4 electrolyte to reshape the interface between ZMA and electrolyte and change the solvation structure of Zn 2+ . Density functional theory (DFT) calculations manifest that the ─C═O, ─Cl, ─C═N─, and ─NO 2 functional groups of CNPM interact with metallic Zn simultaneously and adsorb on the ZMA surface in a parallel arrangement manner, thus forming a water-poor IHL and creating well-arranged ion transportation channels. Furthermore, theoretical calculations and experimental results demonstrate that CNPM absorbed on the Zn anode surface can serve as zincophilic sites for inducing uniform Zn deposition along the (002) plane. Benefiting from the synergistic effect of these functions, the dendrite growth and parasitic reactions are suppressed significantly. As a result, ZMA exhibits a long cycle life (2900 h) and high coulombic efficiency (CE) (500 cycles) in the ZnSO 4 +CNPM electrolyte., (© 2023 Wiley-VCH GmbH.)

The unprecedented global increase in the anthropogenic-derived nitrogen (N) input may have profound effects on phosphorus (P) dynamics and may potentially lead to enhanced eutrophication as demonstrated in short-term mesocosm experiments. However, the role of N-influenced P release is less well studied in large-scale ecosystems. To gain more insight into ecosystem effects, we conducted a five-year large-scale experiment in ten ponds (700-1000 m 2 each) with two types of sediments and five targeted total N concentrations (TN) by adding NH 4 Cl fertilizer (0.5, 1, 5, 10, and 25 mg N L -1 ). The results showed that: (ⅰ) The sediment P release increased significantly when TN exceeded 10-25 mg N L -1 . (ⅱ) The most pronounced sediment P release increase occurred in summer and from sediments rich in organic matter (OM Sed ). (ⅲ) TN, algal biomass, fish biomass, non-algal turbidity, sediment pH, and OM Sed were the dominant factors explaining the sediment P release, as suggested by piecewise structural equation modeling. We propose several mechanisms that may have stimulated P release, i.e. high ammonium input causes a stoichiometric N:P imbalance and induce alkaline phosphatase production and dissolved P uptake by phytoplankton, leading to enhanced inorganic P diffusion gradient between sediment and water; higher pelagic fish production induced by the higher phytoplankton production may have led increased sediment P resuspension through disturbance; low oxygen level in the upper sediment caused by nitrification and organic decomposition of the settled phytoplankton and, finally, long-term N application-induced sediment acidification as a net effect of ammonium hydrolysis, nitrification, denitrification; The mechanisms revealed by this study shed new light on the complex processes underlying the N-stimulated sediment P release, with implications also for the strategies used for restoring eutrophicated lakes., 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 Ltd.)

Objective: To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood., Methods: Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B 1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups., Results: From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group ( P <0.05, P <0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group ( P <0.05, P <0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group ( P <0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group ( P< 0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group ( P <0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group ( P <0.05)., Conclusion: The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.

Black men who have sex with men (MSM) continue to have the highest incidence of new human immunodeficiency virus (HIV) diagnoses in the United States but are least likely to be engaged in care or to be virally suppressed. Many Black MSM face multiple stigmas, but some have found refuge in the House Ball Community (HBC)-a national network of Black lesbian, gay, bisexual, and transgender kinship commitments that provide care-giving, affirmation, and survival skills-building for its members. We propose to modify a skills-building and HIV prevention best-evidence, group-level intervention for HIV- negative Black MSM (Many Men Many Voices) into a family-based intervention to focus on asset-building for both HIV-negative and HIV-positive Black MSM within HBC families. The adapted intervention will be re-branded as Our Family Our Voices (OFOV). We proposed a mixed-methods study to test the feasibility and preliminary efficacy of OFOV adapted for HIV status-neutral use with HBC families. First, we will develop the intervention protocol using the ADAPT-ITT model for modifying behavioral interventions. Then, we will conduct a cluster randomized controlled trial with six HBC families in New York City. Families will be randomized to the OFOV intervention or waitlist control arm. Primary outcomes will be HIV testing, HIV pre-exposure prophylaxis use, currently in HIV care and on HIV treatment. Secondary outcomes will be the number of family-based assets, resilience, number of sexual partners, and relative frequency of condomless anal intercourse. The results of the formative research, including the pilot trial, will contribute to the evidence-base regarding the development of HIV status-neutral interventions that respond to the diversity and complexities of HBC families and that recognize the importance of asset-building for facilitating HBC resilience to stigma as a part of the United States' domestic policy objective of ending the HIV epidemic by 2030., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Birnbaum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sulfonamide antibiotics (SAs) are serious pollutants to ecosystems and environments. Previous studies showed that microbial degradation of SAs such as sulfamethoxazole (SMX) proceeds via a sad-encoded oxidative pathway, while the sulfonamide-resistant dihydropteroate synthase gene, sul, is responsible for SA resistance. However, the co-occurrence of sad and sul genes, as well as how the sul gene affects SMX degradation, was not explored. In this study, two SMX-degrading bacterial strains, SD-1 and SD-2, were cultivated from an SMX-degrading enrichment. Both strains were Paenarthrobacter species and were phylogenetically identical; however, they showed different SMX degradation activities. Specifically, strain SD-1 utilized SMX as the sole carbon and energy source for growth and was a highly efficient SMX degrader, while SD-2 did could not use SMX as a sole carbon or energy source and showed limited SMX degradation when an additional carbon source was supplied. Genome annotation, growth, enzymatic activity tests, and metabolite detection revealed that strains SD-1 and SD-2 shared a sad-encoded oxidative pathway for SMX degradation and a pathway of protocatechuate degradation. A new sulfonamide-resistant dihydropteroate synthase gene, sul918, was identified in strain SD-1, but not in SD-2. Moreover, the lack of sul918 resulted in low SMX degradation activity in strain SD-2. Genome data mining revealed the co-occurrence of sad and sul genes in efficient SMX-degrading Paenarthrobacter strains. We propose that the co-occurrence of sulfonamide-resistant dihydropteroate synthase and sad genes is crucial for efficient SMX biodegradation. KEY POINTS: • Two sulfamethoxazole-degrading strains with distinct degrading activity, Paenarthrobacter sp. SD-1 and Paenarthrobacter sp. SD-2, were isolated and identified. • Strains SD-1 and SD-2 shared a sad-encoded oxidative pathway for SMX degradation. • A new plasmid-borne SMX resistance gene (sul918) of strain SD-1 plays a crucial role in SMX degradation efficiency., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.

Gout is a self-limiting inflammation disease triggered by deposition of monosodium urate with a variety of comorbidities. With the improvement of living standards, the global incidence of gout is increasing year by year, which seriously affects people's health. As an effective tool to study diseases, omics technology has been widely used to discover potential biomarkers and risk factors of gout. The identified variation sites or different-expressed products provide different dimensions of insights for the study of the pathogenesis and disease progression of gout. In this review, the application and research results of multi-omics technology in gout were analyzed and summarized through PubMed literature retrieval. Meanwhile, the recent research progress of multi-omics technology in the field of gout was reviewed to understand the specific changes of gout patients at different molecular levels, and to provide ideas and directions for further research on gout in the future.

Objectives: The specific benefits of a contralateral cervical 7 nerve transplant in people with spastic paralysis of the upper extremity caused by cerebral nerve injury are unclear. To evaluate the efficacy and safety of contralateral C7 nerve transfer for central spastic paralysis of the upper extremity, we conducted a comprehensive literature search and meta-analysis., Materials and Methods: PRISMA guidelines were used to search the databases for papers comparing the efficacy of contralateral cervical 7 nerve transfer vs. rehabilitation treatment from January 2010 to August 2022. The finishing indications were expressed using SMD ± mean. A meta-analysis was used to assess the recovery of motor function in the paralyzed upper extremity., Results: The meta-analysis included three publications. One of the publications offers information about RCTs and non-RCTs. A total of 384 paralyzed patients were included, including 192 who underwent CC7 transfer and 192 who received rehabilitation. Results from all patients were combined and revealed that patients who had CC7 transfer may have regained greater motor function in the Fugl-Meyer score (SMD 3.52, 95% CI = 3.19-3.84, p  < 0.00001) and had superior improvement in range of motion compared to the rehabilitation group (SMD 2.88, 95% CI = 2.47-3.29, p  < 0.00001). In addition, the spasticity in the paralyzed upper extremity significantly improved in patients with CC7 transfer (SMD -1.42, 95% CI = -1.60 to -1.25, p  < 0.00001)., Conclusion: Our findings suggested that a contralateral C7 nerve transfer, which has no additional adverse effects on the healthy upper limb, is a preferable method to restore motor function., 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 Luo, Yan, Guo, Xu and Zhang.)

Background: Fracture repair involves the reactivation of developmental signaling cascades, including Wnt signaling that stimulates bone formation and bone regeneration. Rodent data indicate that dual inhibition of the Wnt signaling antagonists sclerostin and Dickkopf-1 (DKK1) increases callus bone volume and strength while increasing bone mass systemically., Methods: We evaluated the effects of 16 weeks of subcutaneously administered carrier solution (vehicle, VEH), anti-sclerostin antibody (Scl-Ab), anti-DKK1 antibody (DKK1-Ab), or Scl-Ab plus DKK1-Ab combination therapy (COMBO) on ulnar osteotomy healing in nonhuman primates (cynomolgus monkeys; 20 to 22 per group)., Results: Scl-Ab and COMBO therapy increased systemic markers of bone formation versus VEH, with COMBO leading to synergistic increases versus Scl-Ab or DKK1-Ab monotherapies. The COMBO and Scl-Ab groups showed reduced serum markers of bone resorption versus VEH. The COMBO and DKK1-Ab groups exhibited greater callus bone mineral density (BMD), torsional stiffness, and torsional rigidity versus VEH. Lumbar vertebrae from the Scl-Ab and COMBO groups showed greater BMD and bone formation rate versus VEH, and the femoral mid-diaphysis of the Scl-Ab and COMBO groups showed greater periosteal and endocortical bone formation rates versus VEH., Conclusions: DKK1-Ab increased BMD and strength at the ulnar osteotomy site, Scl-Ab increased bone formation and BMD at uninjured skeletal sites, and Scl-Ab plus DKK1-Ab combination therapy induced all of these effects, in some cases to a greater degree versus 1 or both monotherapies. These results in nonhuman primates suggest that DKK1 preferentially regulates bone healing while sclerostin preferentially regulates systemic bone mass., Clinical Relevance: Combination therapy with antibodies against sclerostin and DKK1 may offer a promising therapeutic strategy for both fracture treatment and fracture prevention., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H512 )., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Electrolyte additive is an effective strategy to inhibit the uncontrolled growth of Li dendrites for lithium metal batteries (LMBs). However, most of the additives are complex synthesis and prone to decompose in cycling. Herein, in order to guide the homogeneous deposition of Li + , carbonized polymer dots (CPDs) as electrolyte additives are successfully designed and synthesized by microwave (M-CPDs) and hydrothermal (H-CPDs) approaches. The controllable functional groups containing N or O (especially pyridinic-N, pyrrolic-N, and carboxyl group) enable CPDs to keep stable in electrolytes for at least 3 months. Meanwhile, the clusters formed between CPDs and Li + through electrostatic interaction effectively guide the uniform Li dispersion and limit the "tip effect" and dendrite formation. Moreover, as lithiophilic groups increase, the strong electrostatic interference for the solvation effect of Li + in the electrolyte is formed, which induces faster Li + diffusion/transfer. As expected, H-CPDs achieve the ultra-even Li + transfer. The corresponding Li//LiFePO 4 full cell delivers a high capacity retention rate of 93.8% after 200 cycles, which is much higher than that of the cells without additives (61.2%) and with M-CPDs (83.7%) as additives. The strategy in this work provides a theoretical direction for CPDs as electrolyte additives used in energy storage devices., (© 2023 Wiley-VCH GmbH.)

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.