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Ming Li,1,&ast; Da-Ming Xu,1,&ast; Shu-Bin Lin,1 Zheng-Liang Yang,1 Teng-Yu Xu,1 Jin-Huan Yang,1 Ze-Xin Lin,1 Ze-Kai Huang,1 Jun Yin2,3 1Division of Urological Surgery, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Division of Hematology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun YinDepartment of Clinical Laboratory Medicine and Division of Hematology, The Second Affiliated Hospital of Shantou University Medical College, Dongxia Road North, Shantou, Guangdong Province, 515041, People’s Republic of ChinaTel +86 754 8891 5950Email jyin@stu.edu.cnObjective: To investigate the immune profiles in benign prostatic hyperplasia, changes in the absolute number of lymphocyte subsets and the proportion of T lymphocyte subsets were detected.Methods: Absolute value of lymphocyte subsets in peripheral blood (T, B and NK cells) and the proportion of T lymphocyte (native CD4+ T cell, memory CD4+ T cell, CD8+CD28+ T cell, CD8+CDDR+ T cells and CD8+CD38+ T cell) were measured by flow cytometry.Results: The absolute values of CD3+ T cell (972.55± 330.31 vs 1757.99± 439.38), CD4+ T cell (656.43± 252.39 vs 899.30± 262.10), and CD8+ T cell (301.97± 147.76 vs 728.45± 230.34) in patients with benign prostatic hyperplasia were significantly reduced (all P< 0.05). There was no significant difference in NK cell (285.58± 182.84 vs 528.92± 208.17) and B cell (186.66± 86.62 vs 334.17± 130.46). The proportion of naive CD4+ T cell (3.75± 0.50 vs 8.54± 1.61) in T lymphocyte subsets in patients with BPH was significantly reduced (P< 0.05). There was no significant difference in memory CD4+ T cell (87.9± 6.37 vs 92.63± 5.94), CD8+CD28+ T cell (60.52± 13.86 vs 64.32± 12.78), CD8+CDDR+ T cell (36.58± 12.87 vs 31.92± 8.54) and CD8+CD38+ T cell (2.1± 1.90 vs 2.55± 2.01).Conclusion: Immune dysfunction raised the risk of viral infection, inflammatory stimulation, and tumor induction in prostate cells, leading to hyperplasia, and immune non-response was potentially a key factor in the transformation of BPH into prostate cancer.Keywords: benign prostatic hyperplasia, lymphocyte subsets, pathogenesis, flow cytometry

Yao-Xing Dou,1,2,* Jiang-Tao Zhou,3,4,* Tong-Tong Wang,2 Yan-Feng Huang,1 Vicky Ping Chen,5 You-Liang Xie,1 Zhi-Xiu Lin,6 Jian-Sheng Gao,7 Zi-Ren Su,1 Hui-Fang Zeng2 1Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA; 6School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 7Guangzhou Baiyunshan Mingxing Pharmaceutical Co. Ltd., Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Bruceine D (BD) is a major bioactive component isolated from the traditional Chinese medicinal plant Brucea javanica which has been widely utilized to treat dysentery (also known as ulcerative colitis [UC]). Methods: To improve the water solubility and absolute bioavailability of BD, we developed a self-nanoemulsifying drug delivery system (SNEDDS) composing of MCT (oil), Solutol HS-15 (surfactant), propylene glycol (co-surfactant) and BD. The physicochemical properties and pharmacokinetics of BD-SNEDDS were characterized, and its anti-UC activity and potential mechanism were evaluated in TNBS-induced UC rat model. Results: The prepared nanoemulsion has multiple beneficial aspects including small mean droplet size, low polydispersity index (PDI), high zeta potential (ZP) and excellent stability. Transmission electron microscopy showed that nanoemulsion droplets contained uniform shape and size of globules. Pharmacokinetic studies demonstrated that BD-SNEDDS exhibited enhanced pharmacokinetic parameters as compared with BD-suspension. Moreover, BD-SNEDDS significantly restored the colon length and body weight, reduced disease activity index (DAI) and colon pathology, decreased histological scores, diminished oxidative stress, and suppressed TLR4, MyD88, TRAF6, NF-κB p65 protein expressions in TNBS-induced UC rat model. Conclusion: These results demonstrated that BD-SNEDDS exhibited highly improved oral bioavailability and advanced anti-UC efficacy. In conclusion, our current results provided a foundation for further research of BD-SNEDDS as a potential complementary therapeutic agent for UC treatment. Keywords: bruceine D, self-nanoemulsifying drug delivery system, physicochemical properties, pharmacokinetics, anti-inflammation, anti-colitis activity

Jinming Zhang,1,* Xiaobin Fang,1,* Zeyong Li,2 Hon Fai Chan,3 Zhixiu Lin,4 Yitao Wang,1 Meiwan Chen1 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; 2Department of Laboratory Medicine, Guangdong No 2 Provincial People’s Hospital, Guangzhou, China; 3Department of Biomedical Engineering, Columbia University, New York, NY, USA; 4Faculty of Science, School of Chinese Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China *These authors contributed equally to this work Abstract: Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as ­apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway. Keywords: poloxamer188, tumor micro-environment, glutathione, Brucea javanica, cancer treatment

Jiawu Fu,1,* Guoda Ma,1,* Hui Mai,1,* Xudong Luo,2 Jingwen Yin,2 Qing Chen,2 Zhixiong Lin,2 Hua Tao,1 You Li,1 Lili Cui,1 Zheng Li,3 Juda Lin,2 Bin Zhao,1 Keshen Li1 1Institute of Neurology, Affiliated Hospital of Guangdong Medical University, 2Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China; 3Unit on Synapse Development and Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA *These authors contributed equally to this work Abstract: Sepiapterin reductase participates in the biosynthesis of tetrahydrobiopterin, which plays very important roles in the pathogenesis of schizophrenia via dysregulation of ­neurotransmitter systems. Here, two single nucleotide polymorphisms (rs1876487 and rs2421095) in the promoter region of SPR were genotyped in 941 schizophrenic patients and 944 controls in a Han Chinese population using the SNaPshot technique. No significant differences were found in the distribution of alleles or genotypes of the two single nucleotide polymorphisms (SNPs) between schizophrenic patients and controls (all P>0.05). Likewise, no haplotype was found to be associated with schizophrenia. However, sex-stratified analysis revealed that the frequencies of the A allele of rs1876487 and the A–A (rs2421095–rs1876487) haplotype were all significantly different between schizophrenia and controls in females (P=0.040 and P=0.033, respectively), but not in males. Additionally, luciferase reporter gene assays revealed that the A–A haplotype had significantly higher SPR transcriptional activity compared with the A–C haplotype in SH-SY5Y cells. Our data indicate that the two SNPs do not influence the risk of schizophrenia when using the total sample, but the A allele of rs1876487 and the A–A haplotype may contribute to protective roles for schizophrenia in females. Keywords: schizophrenia, sepiapterin reductase, polymorphisms, Han Chinese population, transcriptional activity

The human lung carcinoma cell line PG is defective in gap junctional intercellular communication (GJIC). Connexin43 (Cx43) mRNA, which is expressed in normal human lung cells, is undetectable in these tumor cells. To explore if up-regulation of Cx43 gene expression will suppress malignancy of PG cells, Cx43 cDNA was co-transfected with pSV2neo cDNA into PG cells. Control cells were transfected with the blank vector plus neo cDNA. Several stable Cx43 transfectant clones, which acquired high levels of Cx43 expression and the capacity of GJIC, were compared with control clones and the parental cell line, both of which lacked Cx43 expression and GJIC. The control clones resembled the parental cells in exhibiting high cell growth rate, weak attachment to the substratum and a high frequency of colony formation in soft agar. In contrast to the control cells, Cx43 transfected clones showed reduced growth rate, enhanced attachment to the substratum and inhibition of colony formation in soft agar. In vivo results from nude mice experiments showed high tumorigenicity with control clones and inhibition of tumorigenicity in Cx43 transfected clones. The consistency between in vitro and in vivo results strongly suggests a tumor suppressing effect of the Cx43 gene in human lung carcinoma cells. [ABSTRACT FROM PUBLISHER]

Objective: Human umbilical cord mesenchymal stem cells (hUCMSCs) hold significant promise across various clinical applications. Therefore, regulatory requirements necessitate a thorough investigation of the hUCMSCs safety before clinical trials and potential allergic reactions after transplantation., Methods: Abnormal toxicity test employed mice and guinea pigs dosed daily at 0.5×106 cells and 5×106 cells, respectively for 7 days. Acute toxicity test employed low, medium, and high doses of hUCMSCs injected into mice once, followed by observations for 23 days. In systemic allergy test, guinea pigs received low and high dose of hUCMSCs, with sensitization and excitation stages at day 14 and 21, respectively., Results: The abnormal toxicity test of hUCMSC injections revealed no abnormal reactions over a seven-day observation period, indicating the safety of this administration route. In acute toxicity studies, the high-dose hUCMSCs group resulted in fatalities due to pulmonary embolism. Conversely, the low-dose group exhibited no toxic reactions or deaths. The maximum tolerated dose was determined to be >2×107 cells/kg. Systemic active allergy test showed that high doses of hUCMSC intravenous injections did not induce allergic reactions., Conclusion: This research affirms hUCMSC injections meet safety standards for clinical cell therapy, emphasizing their safe and promising clinical utility., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cheng 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.)

Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM's role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice., (© 2024. The Author(s).)

Introduction: We describe female authorship trends in gastroenterology (GI) randomized controlled trial literature as a novel focus on gender bias in academic GI., Methods: Using a systematic PubMed search, we extracted GI randomized controlled trial reports published from 2011 to 2022. We describe time trends in proportions of females among first and last authors overall and within GI subspecialties and high-impact journals., Results: The proportion of females increased from 25.4% to 36.8% and from 14.3% to 24.8% among first and last authors, respectively. Smaller increases in female authorship occurred in most subgroups, although there were proportionately fewer females among authors in high-impact journals and advanced therapeutic endoscopy publications., Discussion: Over the past decade, female authorship in GI RCT reports has increased. However, female representation, particularly among senior authors and in high-impact journals, remains significantly lower. Despite recent improvements, female still constitutes a minority of the authors of original GI RCTs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

In an era of medicine when a paternalistic approach was the norm, neurologist Dr. Oliver Sacks infused his care with humanity, centering a dialogue that emphasized his patients' perspective and personhood. For most of his life, he encountered significant personal challenges, and struggled with prosopagnosia and an internal conflict with his sexuality. Instead of allowing these challenges to hold him back, he transformed them into the driving force behind a career that uniquely combined the scientific beauty of neurology and a humanistic patient-centered approach with the power of literature. Through non-fiction works like Awakenings and The Man Who Mistook His Wife for a Hat , he translated the overwhelming complexities of neurological disorders into stories that touched the hearts of readers around the world, making the science of the brain more accessible and human. In his later years, Dr. Sacks grappled with his mortality and the broader questions of aging and life's purpose, themes central to his final book, Gratitude . His reflections emphasized the importance of aligning healthcare with patients' personal values and goals. Dr. Sacks' legacy is marked not only by his professional contributions and literary achievements but also by his deep compassion and innovative approach to patient care, which continues to influence modern medical practice and inspire an ongoing discourse about the intersection of science, humanity, and individual experience., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sharon et al.)

Transition metals are promising catalysts for environmental remediation. However, their low reactivity, poor stability and weak reusability largely limit practical applications. Herein, we report that the electron-rich dissolved black carbon (DBC) incorporated into the nanoscale zero-valent copper (nZVCu) can boost intrinsic reactivity, structural stability and cyclic reusability for superior peroxymonosulfate (PMS) activation and pollutant degradation. A series of refractory pollutants can be effectively removed on the DBC/nZVCu, in comparison with the nZVCu reference. Hydroxyl radical (‧OH) is identified as the dominant reactive oxygen species by electron spin resonance (ESR) and chemical quenching tests, mediated by the metastable Cu(III) as the key reactive intermediate. The electron-rich DBC protects nanoscale Cu from oxidative corrosion to slow down the surface formation of inert CuO layer, rendered by the thermodynamically and dynamically capacitive regulation of corrosive electron transfer from metallic core. By this refining way, the conducive DBC improves the neighboring utilization of reactive electron during metal corrosion, oxidant activation, radical generation and pollutant degradation in Fenton-like catalysis. Our findings suggest that the ubiquitous DBC can be an efficient chelating agent to refine transition metals by serving as the surface deactivator and electron mediator, and take new insights into their environmental and agricultural geochemistry., 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 B.V. All rights reserved.)

Introduction: Gemcitabine (GEM) is the first-line drug for pancreatic ductal adenocarcinoma (PDAC), but drug resistance severely restricts its chemotherapeutic efficacy. Laminin subunit γ2 (LAMC2) plays a crucial role in extracellular matrix formation in the development of GEM-resistance. However, the biological function of LAMC2 in GEM resistance and its molecular mechanisms are still unclear. 20(S)-Ginsenoside Rh2 (Rh2), one of the principal active components isolated from Ginseng Radix et Rhizoma, possesses strong anti-tumor effects. However, the effects of Rh2 on overcoming GEM resistance and its action mechanisms remain to be elucidated., Objectives: This study aimed to determine the efficacy of Rh2 on overcoming GEM resistance and to explore its underlying molecular mechanisms., Methods: Clinical study, Western blotting, publicly available databasesand bioinformatic analyses were performed to investigate the protein expression of LAMC2 in the GEM-resistant PDAC patients and the acquired GEM-resistant PDAC cells. Then, the effects of Rh2 on overcoming the GEM resistance in PDAC were evaluated both in vitro and in vivo. Stable silencing or overexpression of LAMC2 in the GEM-resistant PDAC cells were established for validating the role of LAMC2 on Rh2 overcoming the GEM resistance in PDAC., Results: The protein expression of LAMC2 was markedly increased in the GEM-resistant PDAC patient biopsies compared to the sensitive cases. The protein expression of LAMC2 was significantly higher in the acquired GEM-resistant PDAC cells than that in their parental cells. Rh2 enhanced the chemosensitivity of GEM in the GEM-resistant PDAC cells, and inhibited the tumor growth of Miapaca-2-GR cell-bearing mice and Kras tm4Tyj Trp53 tm1Brn Tg (Pdx1-cre/Esr1*) #Dam/J (KPC) mice. Rh2 effectively reversed the GEM resistance in Miapaca-2-GR and Capan-2-GR cells by inhibiting LAMC2 expression through regulating the ubiquitin-proteasome pathway. Knockdown of LAMC2 enhanced the chemosensitivity of GEM and the effects of Rh2 on overcoming the GEM resistance in PDAC cells and the orthotopic PDAC mouse model. Conversely, LAMC2 overexpression aggravated the chemoresistance of GEM and abolished the effects of Rh2 on overcoming GEM resistance via modulating ATP-binding cassette (ABC) transporters leading to the active GEM efflux., Conclusions: LAMC2 plays an important role in the GEM resistance in PDAC, and Rh2 is a potential adjuvant for overcoming the chemoresistance of GEM in PDAC., 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. Production and hosting by Elsevier B.V.)

Transition metals exhibit high reactivity for Fenton-like catalysis in environmental remediation, but how to save consumption and reduce pollution is of great interest. In this study, rationally designed defect-engineered Fe@MoS 2 (Fe@D-MoS 2 ) was prepared by incorporating reactive iron onto structural defects generated from the chemical acid-etching, aiming to improve the energetic consumption of the catalyst in Fenton-like applications. Morphological and structural properties were elucidated in details, the Fenton-like reactivity was evaluated with five phenolic contaminants for oxidant activation, radical generation and environmental remediation. Compared to Fe@MoS 2 , Fe@D-MoS 2 exhibited a 18.9-fold increase in phenol degradation (0.09 versus 1.79 min -1 ). Quenching experiments, electron paramagnetic resonance tests and electrochemical measurements revealed the dominant sulfate and superoxide radicals. Rendered by strong metal-substrate surface and electronic interactions from regulated chemical environment and coordination structure, the inert ≡ Fe(III) was reduced to the reactive ≡ Fe(II) accompanied by the ≡ Mo(IV) oxidation to ≡ Mo(V) in MoS 2 lattice, with adjacent sulfur serving as the key electron transfer bridge. Therefore, this work shows that the incorporation of reactive centers is able to boost two-dimensional sulfide materials for environmental catalysis applications., 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 Ltd. All rights reserved.)

Background: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored., Methods: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Kras tm4Tyj Trp53 tm1Brn Tg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model., Results: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression., Conclusions: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Upper limb problems have a significant impact on the global population leading to pain and restricted joint mobility, ultimately impacting their quality of life. Traditional treatments, such as non-steroidal anti-inflammatory drugs and corticosteroids, often come with undesirable side effects, prompting patients to seek alternative therapies. In this trial, we hypothesise that soothing cream gel (SCG) will improve range of motion and chronic pain in the shoulder and elbow. The objective of this trial is to evaluate the efficacy of SCG in improving the range of motion and chronic pain in the shoulder and elbow., Methods and Analysis: A double-blinded, randomised, placebo-controlled trial is conducted to compare the effects of SCG and placebo gel. SCG contains Vitis vinifera essence, Melaleuca viridiflora essential oil, etc, and is manufactured according to Good Manufacturing Practice standards. The placebo gel will be processed with similar appearance, texture and scent but will lack active ingredients. 70 participants with upper limb problems will be recruited from four study sites, including clinical centres and a sport department at the Chinese University of Hong Kong (CUHK). Participants will be randomly assigned to either treatment group or placebo group for 2 weeks. Primary outcome will be the range of motion in the upper limb, assessed by a goniometer, to measure active flexion and abduction for the shoulder, and active flexion and extension for the elbow. The primary efficacy analyses will be based on the full analysis set following the intention-to-treat principle., Ethics and Dissemination: The trial has obtained approval from the joint CUHK-New Territories East Cluster (CRE-2023.142), and the patient enrolment commenced in July 2023. Written informed consent will be obtained from all participants prior to participation. Study results will be disseminated through publication in peer-reviewed journals and presentations at conference., Trial Registration Number: NCT05799391., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ethnopharmacological Relevance: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored., Aim of the Study: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models., Methods: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP., Results: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aβ) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aβ production enzymes such as β- and γ-secretases and activating Aβ degrading enzyme to reduce Aβ accumulation. In addition, TGP reduced the Aβ 42 level, the ratio of Aβ 42 /Αβ 40 , Aβ accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice., Conclusion: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aβ aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical., Competing Interests: Declaration of competing interest All authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influent our work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases., (© 2024. The Author(s).)

A traditional Chinese herbal medicine formula named Huang-Lian-Jie-Du Decoction (HLJDD) has been used to cure various inflammatory diseases with a long history. However, one component of HLJDD Gardeniae fructus has remarkable liver and kidney toxicities. Therefore, it was altered with Dictamni cortex to form a modified HLJDD (MHLJDD). In this study, we aimed to evaluate the sub-chronic toxicity of the active fraction of MHLJDD (MHLJDD-F) in rats. Adult rats of both sexes were intragastrically administered with vehicle or MHLJDD-F (at the dose of 170, 340, and 680 mg/kg/day) once daily for 90 days. Half of the rats from each group were kept for an additional 30-day period to observe the drug withdrawal effect. The signs of toxicity and mortality of the rats were observed, and the body weight and food consumption were recorded. Blood was collected for hematological and biochemical analyses and major organs were weighed and harvested for histopathological examinations. The results revealed that no systemic toxicity of MHLJDD-F was found during the experiments. Organ coefficients and pathological alterations of major organs were comparable to the control rats. The no-observed adverse effect level (NOAEL) of MHLJDD-F was found up to 680 mg/kg/day. All these results demonstrated that long-term oral administration of MHLJDD-F did not cause significant toxicity, which is worthy to be widely applied as a new herbal medicine in pre-clinical and clinical studies., 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.)

Background: Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades., Aims: To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats., Methods: Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined., Results: The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1β, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application., Conclusions: ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose., (© 2024. The Author(s).)

Purpose: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues., Methods: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated., Results: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells., Conclusion: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Pectus excavatum (PE) is a congenital defect that presents with an anterior depression of the chest wall, which can impact cardiopulmonary function. A 25-year-old hypermobile male presented with a history of PE and chronic dyspnea on exertion, chronic cough, and intermittent chest wall pain. This study explores osteopathic manipulative treatment (OMT) as a possible alternative to improve symptoms associated with PE. Osteopathic structural exam (OSE), volumetric measurements of the thoracic cavity, vitals, and pulmonary function tests were evaluated at baseline and after OMT. The patient was treated with 14 weeks of weekly OMT for his exertional dyspnea, cough, and chest wall pain. Somatic dysfunctions were addressed through OMT, which all improved by the end of the 14-week treatment. Notably, the excursion at the sternal angle increased by threefold after complete treatment. The patient reported subjective improvement in all symptoms, with durable improvement in chest wall pain at 10 months after cessation of treatment. The application of OMT can help alleviate symptoms of pectus excavatum and aid in the management of patients who have not received surgical interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Lin et al.)

Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Li et al.)

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis., Patients & Methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model., Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908)., Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis., 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., (© 2024 Yu, Zhang, Xu, Lin, Guo, Li, Huang and Huang.)

Ubiquitous humic substances usually exhibit strong interfering effects on target pollutant removal in advanced water purification. This work aims to develop a photochemical conversion system on the nonstoichiometric TiO 2 for pollutant removal in environmentally relevant matrices. In this synergistic reaction system, the redox-reactive humic substances and defective oxygen vacancies can serve as the organic electron transfer mediator and the key surface reactive sites, respectively. This system achieves a superior pollutant degradation in real surface water at low oxidant concentrations. Reactive oxygen vacancies on the TiO 2 surface and sub-surface are of considerable interest for this photochemical reaction system. By engineering defective oxygen vacancies on high-energy {001} polar facet, the surface and electronic interactions between tailored TiO 2 and humic substances are greatly strengthened for the promoted electron transfer and oxidant activation. Rendered by the strong surface affinity and molecular activation, defective oxygen vacancies thermodynamically and dynamically promote reactive chain reactions for free radical formation, including the selective O 2 reduction to ·O 2 - and the H 2 O 2 activation to ·OH. Our findings take new insights into environmental geochemistry, and provide an effective strategy to in-situ boost the humic substances-mediated water purification without secondary pollution. ENVIRONMENTAL IMPLICATION: Humic substances are widely distributed in aquatic environment, thus playing important roles in environmental geochemistry. For example, humic substances can achieve good surface adsorption through electrostatic adsorption, ligand exchange and electronic interactions with typical TiO 2 to form reactive ligand-metal charge transfer complexes for pollutant degradation. Inspired by the unique properties of surface and sub-surface oxygen vacancies, the defective TiO 2 was designed to refine the humic substances-mediated photochemical reactions. A superior reactivity was measured for pollutant degradation. Our findings provide an effective strategy to boost naturally photochemical decontamination in environmentally relevant matrices., 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 B.V. All rights reserved.)

A water-soluble glycopeptide (named GL-PWQ 3 ) with a molecular weight (M w ) of 2.40 × 10 4  g/mol was isolated from Ganoderma lucidum fruiting body by hot water extraction, membrane ultrafiltration, and gel column chromatography, which mainly consisted of glucose and galactose. Based on the methylation, FT-IR, 1D, and 2D NMR analysis, the polysaccharide portion of GL-PWQ 3 was identified as a glucogalactan, which was comprised of unsubstituted (1,6-α-Galp, 1,6-β-Glcp, 1,4-β-Glcp) and monosubstituted (1,2,6-α-Galp and 1,3,6-β-Glcp) in the backbone and possible branches that at the O-3 position of 1,3-Glcp and T-Glcp, and the O-2 position of T-Fucp, T-Manp or T-Glcp. The chain conformational study by SEC-MALLS-RI and AFM revealed that GL-PWQ 3 was identified as a highly branched polysaccharide with a polydispersity index of 1.25, and might have compact sphere structures caused by stacked multiple chains. Moreover, the GL-PWQ 3 shows strong anti-oxidative activity in NRK-52E cells. This study provides a theoretical basis for further elucidating the structure-functionality relationships of GL-PWQ 3 and its potential application as a natural antioxidant in pharmacotherapy as well as functional food additives., Competing Interests: Declaration of competing interest The author reports no declaration of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Qing-Zao-Jiu-Fei Decoction (QZJFD) is a famous herbal formula commonly prescribed for the treatment of lung-related diseases in the ancient and modern times. Trichosanthis Fructus (TF) and Fritillariae Thunbergii Bulbus (FTB) are widely used for treatment of cough and pulmonary disease. In order to identify a more effective formula for treatment of pulmonary fibrosis, we intend to add TF and FTB in QZJFD to form a modified QZJFD (MQZJFD). In this study, we aims to explore MQZJFD as an innovative therapeutic agent for pulmonary fibrosis using bleomycin (BLM)-treated rats and to unravel the underlying molecular mechanisms., Methods: BLM was given to SD rats by intra-tracheal administration of a single dose of BLM (5 mg/kg). QZJFD (3 g/kg) and MQZJFD (1, 2 and 4 g/kg) was given intragastrically daily to rats for 14 days (from day 15 to 28) after BLM administration for 14 consecutive days., Results: MQZJFD was found to contain 0.29% of amygdalin, 0.020% of lutin, 0.077% of glycyrrhizic acid and 0.047% of chlorogenic acid. BLM treatment could induce collagen deposition in the lung tissues of rats, indicating that the pulmonary fibrosis rat model had been successfully established. MQZJFD have better effects than the original QZJFD in reducing the pulmonary structure damage and collagen deposition of rat lung fibrosis induced by BLM. MQZJFD could reduce the hydroxyproline content in lung tissues of BLM-treated rats. The biomarkers of fibrosis such as matrix metalloproteinase 9 (MMP9), collagen I and α-smooth muscle actin (α-SMA) were remarkably reduced after treatment with MQZJFD. MQZJFD also have anti-oxidant stress effects by inhibiting the level of malondialdehyde (MDA), but enhancing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the level of glutathione (GSH) in the lung tissues of BLM-treated rats. Moreover, the MQZJFD markedly suppressed the over expressions of p-p65/p65 and p-IκBα/IκBα, but upregulated the Nrf2. MQZJFD also suppressed the protein expressions of p-ERK1/2/ERK1/2, p-p38/p38 and p-JNK/JNK in the lung tissues of BLM-treated rats., Conclusions: MQZJFD could improve the pulmonary fibrosis induced by BLM in rats via inhibiting the fibrosis and oxidative stress via suppressing the activation of NF-κB/Nrf2 and MAPKs pathways., (© 2024. The Author(s).)

A conformal cooling channel (CCC) follows the mold core or cavity profile to carry out uniform cooling in the cooling stage. However, the significant pressure drop along the cooling channels is a distinct disadvantage of the CCC. In this study, an innovative waterfall cooling channel (WCC) was proposed and implemented. The WCC cools the injected products via surface contact, replacing the conventional line contact to cool the injected products. The WCC was optimized using numerical simulation software. Silicone rubber molds with two kinds of cooling channels were designed and implemented. The cooling time of the molded part was evaluated using a low-pressure wax injection molding machine. The experimental results of the cooling time of the molded part were compared with the simulation results from numerical simulation software. The results showed that the optimal mesh element count was about 1,550,000 with a mesh size of 1 mm. The simulation software predicted the filling time of the water cup injection-molded product to be approximately 2.008 s. The cooling efficiency for a silicone rubber mold with a WCC is better than that of the silicone rubber mold with a CCC since the core and cavity cooling efficiency is close to 50%. The pressure drop of the WCC is smaller than that of the CCC, which reduces the pressure drop by about 56%. Taking a water cup with a mouth diameter of 70 mm, a height of 60 mm, and a thickness of 2 mm as an example, the experimental results confirmed that the use of the WCC can save the cooling time of the product by about 265 s compared with the CCC. This shows how a WCC can increase cooling efficiency by approximately 17.47%.

Background: The Coronavirus disease 2019 (COVID-19) is the largest global epidemic in recent time. Chinese medicine has been recognized by the World Health Organization as an effective treatment for COVID-19, but there is still a lack of high-quality randomized, double-blind trials using placebo as the control to support its application, which may hinder its further promotion locally and internationally. Objectives: This study will evaluate the efficacy and safety of Yinqiao Powder-Maxing Ganshi Decoction with variation in relieving major symptoms of mild and moderate COVID-19 by telemedicine. Methods and design: This clinical study is a randomized, double-blind, placebo-controlled trial that applies telemedicine to evaluate the efficacy and safety of Yinqiao Powder-Maxing Ganshi Decoction in the treatment of mild and moderate COVID-19. Eligible subjects will be randomly divided into either treatment or placebo groups for up to 14 days after stratification according to age (A:18-49, B:50-65) and the number of vaccinations (a: ≥3 doses, b: ≤2 doses). The treatment group will receive Yinqiao Powder-Maxing Ganshi Decoction granules along with certain variation based on their symptoms, and the placebo group will receive the same amount of placebo granules. Subjects will be prescribed different additions based on their symptoms and pathogenesis at the inclusion. The oral temperature, oximeter, result of rapid antigen test and symptom score will be recorded by subjects until they have stopped the medication. Subjects are required to have follow-up assessment by video-conference on days 7, 14 and 35. The time for the body temperature returning to normal will be used as the primary outcome. Discussion: This trial will provide scientific evidence on the use of Yinqiao Powder-Maxing Ganshi Decoction for the treatment of COVID-19, and the results would help raise the awareness in Hong Kong and the international community on the use of Chinese herbal medicine for treating COVID-19. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05787327., 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 Sum, Li, Zhang, Hung, Fong, Lin, Chow, Leung, Lo, Chia, Chan and Lin.)

Background: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identification and clinical significance of efferocytosis-related genes (EFRGs) in EM is sparse. Methods: The EFRDEGs (differentially expressed efferocytosis-related genes) linked to datasets associated with endometriosis were thoroughly examined utilizing the Gene Expression Omnibus (GEO) and GeneCards databases. The construction of the protein-protein interaction (PPI) and transcription factor (TF) regulatory network of EFRDEGs ensued. Subsequently, machine learning techniques including Univariate logistic regression, LASSO, and SVM classification were applied to filter and pinpoint diagnostic biomarkers. To establish and assess the diagnostic model, ROC analysis, multivariate regression analysis, nomogram, and calibration curve were employed. The CIBERSORT algorithm and single-cell RNA sequencing (scRNA-seq) were employed to explore immune cell infiltration, while the Comparative Toxicogenomics Database (CTD) was utilized for the identification of potential therapeutic drugs for endometriosis. Finally, immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to quantify the expression levels of biomarkers in clinical samples of endometriosis. Results: Our findings revealed 13 EFRDEGs associated with EM, and the LASSO and SVM regression model identified six hub genes (ARG2, GAS6, C3, PROS1, CLU, and FGL2). Among these, ARG2, GAS6, and C3 were confirmed as diagnostic biomarkers through multivariate logistic regression analysis. The ROC curve analysis of GSE37837 (AUC = 0.627) and GSE6374 (AUC = 0.635), along with calibration and DCA curve assessments, demonstrated that the nomogram built on these three biomarkers exhibited a commendable predictive capacity for the disease. Notably, the ratio of nine immune cell types exhibited significant differences between eutopic and ectopic endometrial samples, with scRNA-seq highlighting M0 Macrophages, Fibroblasts, and CD8 Tex cells as the cell populations undergoing the most substantial changes in the three biomarkers. Additionally, our study predicted seven potential medications for EM. Finally, the expression levels of the three biomarkers in clinical samples were validated through RT-qPCR and IHC, consistently aligning with the results obtained from the public database. Conclusion: we identified three biomarkers and constructed a diagnostic model for EM in this study, these findings provide valuable insights for subsequent mechanistic research and clinical applications in the field of endometriosis., 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 Pei, Jia, Lin, Chen, Wu, Lin, Sun and Zeng.)

Gut dysbiosis, a well-known risk factor to triggers the progression of Alzheimer's disease (AD), is strongly associated with metabolic disturbance. Trimethylamine N -oxide (TMAO), produced in the dietary choline metabolism, has been found to accelerate neurodegeneration in AD pathology. In this study, the cognitive function and gut microbiota of TgCRND8 (Tg) mice of different ages were evaluated by Morris water maze task (MWMT) and 16S rRNA sequencing, respectively. Young pseudo germ-free (PGF) Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type (WT) mice were selected to determine the role of the gut microbiota in the process of neuropathology. Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions. Our results showed that gut dysbiosis, neuroinflammation response, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and cyclin-dependent kinase 5 (CDK5)/transcription 3 (STAT3) activation occurred in Tg mice age-dependently. Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice, with the activation of CDK5/STAT3 signaling in the brains. On the contrary, faecal microbiota transplantation from WT mice alleviated the cognitive deficits, attenuated neuroinflammation, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice. Moreover, excessive choline treatment was also shown to aggravate the cognitive deficits, Aβ deposition, neuroinflammation and CDK5/STAT3 pathway activation. These findings provide a novel insight into the interaction between gut dysbiosis and AD progression, clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV., Competing Interests: Declaration of Competing Interest No conflicts of interest exist for any of the authors., (Copyright © 2023. Published by Elsevier Inc.)

Masses of iron sludge generated from engineering practice of classic Fenton reaction constraints its further promotion. Accelerating the Fe III /Fe II cycle may be conducive to reducing the initial ferrous slat dosage and the final iron sludge. Based on the reduction of Pd/MIL-100(Fe)-activated hydrogen, an improved Fenton system named MHACF-MIL-100(Fe) was developed at ambient temperature and pressure. 97.8% of sulfamethazine, the target pollutant in this work, could be degraded in 5 min under the conditions of 20 mM H 2 O 2 , 25 μM ferrous chloride, initial pH 3.0, 2 g·L -1 composite catalyst Pd/MIL-100(Fe) and hydrogen gas 60 mL·min -1 . Combining density functional theory (DFT) calculation and intermediate detection, the degradation of this antibiotic was inferred to start from the cleavage of N-S bond. The catalytic of Pd/MIL-100(Fe), demonstrated by the removal efficiency of SMT and the catalyst morphology, remained intact after six reaction cycles. The present study provides an insight into the promotion of Fenton reaction.