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Jia Hou, Jin-Feng Li, Xiu-Juan Yan, Yong-Liang Zhang, Meng-Yu Zhang, Yuan Zhang Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, People’s Republic of ChinaCorrespondence: Yuan Zhang, Department of Pharmacy, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, No. 70 Heping Road, Huancui District, Weihai City, Shandong Province, 264200, People’s Republic of China, Tel +86-18660377685, Email yuany20222022@163.comObjective: The purpose of this study was to analyze the improvement effect of clinical pharmacist intervention on renal function impairment in patients with antimicrobial-induced acute kidney injury (AKI).Methods: A total of 145 patients with AKI caused by antibiotics admitted to the ICU department were selected as the research subjects. The patients were divided into the control group (n=57) and the intervention group (n=88) according to whether there were ICU specialist clinical pharmacists involved in clinical treatment. The renal function outcome and infection control were evaluated in the two groups.Results: The proportion of renal function outcome in the intervention group was 88.6%, which was significantly higher than that in the control group. However, there was no statistically significant difference in infection control between the two groups. For the intervention group, the clinical pharmacists adopted three intervention methods: dose adjustment, drug replacement and CRRT treatment, respectively, according to the disease conditions of AKI patients. Among them, dose adjustment and drug replacement were the most frequently used intervention methods. In addition, the proportion of renal function outcome was higher in the group of patients who changed antibiotics and underwent CRRT, which were 93.1% and 100%, respectively. The adjusted-dose group had the highest infection control rate at 82.1%. However, there were no statistically significant differences in renal function outcomes and infection control among the three interventions.Conclusion: Clinical pharmacists participating in the clinical treatment of patients with antimicrobial-induced AKI in ICU can effectively improve the renal function of patients.Keywords: clinical pharmacists, acute kidney injury, antimicrobial, renal function

Cheng-Jun Zhuge,1 Cheng-Peng Zhan,2 Ke-Wei Wang,1 Xin-Jiang Yan,2 Guo-Feng Yu2 1The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Neurosurgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, People’s Republic of ChinaCorrespondence: Guo-Feng Yu, Tel +86 570 3055179, Email quzhouguofengyu@163.comObjective: Sulfonylurea receptor-1 (SUR1) is implicated in acute brain injury. This study was designed to determine relationship between serum SUR1 levels and severity, early neurologic deterioration (END) plus clinical outcome after intracerebral hemorrhage (ICH).Methods: Serum SUR1 levels of 131 ICH patients and 131 healthy controls were quantified in this prospective, observational study. END was defined as an increase of 4 or more points in the National Institutes of Health Stroke Scale (NIHSS) score or death within 24 hours after admission. Patients with a modified Rankin scale (mRS) score of 3– 6 at 90 days following onset were considered to experience a poor outcome.Results: Serum SUR1 levels were substantially higher in patients than in controls. Serum SUR1 levels of patients were highly correlated with NIHSS score, Glasgow Coma Scale score, hematoma volume and ICH score. Compared with patients with END or mRS score of 0– 2, other remainders had significantly elevated serum SUR1 levels. Serum SUR1 levels independently predicted END and 90-day poor outcome. Under receiver operating characteristic curve, serum SUR1 levels significantly predicted END and a poor outcome at 90 days after hemorrhagic stroke and its predictive value was similar to those of NIHSS score, Glasgow coma scale score, hematoma volume and ICH score.Conclusion: Serum SUR1 levels are highly correlated with severity, END and poor outcome after hemorrhagic stroke, indicating that serum SUR1 may be useful for risk stratification and prognostic prediction of ICH.Keywords: Sulfonylurea receptor-1, intracerebral hemorrhage, early neurologic deterioration, functional outcome, severity

Xin-Jiang Yan,1 Yang-Bo Li,1 Wei Liu,1 Hua-Yong Wu,2 Guo-Feng Yu1 1Department of Neurosurgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, People’s Republic of China; 2Neurosurgical Intensive Care Unit, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, People’s Republic of ChinaCorrespondence: Guo-Feng Yu Tel +86 570 3055179Email yuguofeng79@aliyun.comObjective: Complement C1q is implicated in neuroinflammation. We intended to discern the relationship between serum C1q levels and severity in addition to prognosis following traumatic brain injury (TBI).Methods: In this prospective, observational study, serum C1q levels were quantified in 188 TBI patients and 188 healthy controls. Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification were used as clinical and radiological indicators of severity. Patients with extended Glasgow outcome scale (GOSE) score of 1– 4 at 6 months after trauma were considered to have a poor outcome. Multiple logistic regression model was built to ascertain the independent association of serum C1q levels with 6-month poor outcome. Receiver operating characteristic (ROC) curve was configured for analysis of prognostic capability with respect to serum C1q levels.Results: TBI patients exhibited substantially higher serum C1q levels than controls (median, 223.9 mg/l versus 75.4 mg/l). Serum C1q levels of patients were tightly correlated with GCS score (r = − 0.671), Rotterdam CT classification (r = 0.604) and GOSE score (r = − 0.581). An area under the ROC curve was yielded of 0.793 (95% confidence interval = 0.728– 0.849), and serum C1q levels above 345.5 mg/l discriminated the risk of 6-month poor outcome with 59.6% sensitivity and 92.6% specificity. Serum C1q levels above 345.5 mg/l retained as an independent predictor for 6-month poor outcome with odds ratio of 4.922 (95% confidence interval = 1.552– 15.606; P = 0.017).Conclusion: Elevated serum C1q levels are closely correlated with traumatic severity and independently predicted the risk of long-term poor prognosis after TBI.Keywords: traumatic brain injury, C1q, severity, functional outcome, biomarkers

Yuan-Yuan Du, Xiao-Jing Yan, Yan-Jing Guo, Jing Wang, Xiao-Duo Wen, Nan Wang, Yi Yang Department of Gynecology and Obstetrics Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Yi YangDepartment of Gynecology and Obstetrics Ultrasound, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Chang’an District, Shijiazhuang, 050011, People’s Republic of ChinaTel/Fax +86 311 8609 5378Email yangyi_dr336@163.comBackground: To explore the value of transvaginal real-time shear wave elastography (SWE) in the diagnosis of endometrial lesions.Methods: A total of 140 female patients with endometrial lesions, confirmed by pathological results, were divided into three groups: 45 cases of endometrial polyps, 29 cases of endometrial hyperplasia and 66 cases of endometrial cancer. A total of 100 cases of normal endometrium were used as the control group, including 52 cases in the proliferative stage and 48 cases in the secretory stage. Transvaginal real-time shear wave elastography was performed in all four groups.Results: Emean, Emax and Esd were expressed as the average standard deviation. Among the control group, the results were 26.24± 9.74, 38.09± 9.18, and 4.25± 2.73 kPa, respectively, in the proliferative endometrium cases and 12.51± 7.46, 27.22± 11.32, 4.40± 2.52 kPa, respectively, in the secretory endometrium cases. Among the experimental group, the result was 15.68± 8.18, 27.28± 10.28 and 3.62± 1.81 kPa respectively in the endometrial polyps cases; 21.20 ± 12.57, 36.32 ± 15.04, and 5.09 ± 3.93 kPa in the endometrial hyperplasia cases; 49.36± 25.51, 86.66± 42.27 and 14.86± 10.63 kPa in the endometrial cancer cases. The difference was statistically significant (P < 0.05). When the truncation values of Emean, Emax and Esd were 28.50, 52.45 and 9.05 kPa, respectively, to distinguish between normal endometrium and endometrial cancer, Emax has the highest diagnostic value.Conclusion: Real-time SWE technology might be used as an auxiliary method in the diagnosis and differential diagnosis of endometrial cancer. More quantitative indicators are conducive to diagnosis.Keywords: ultrasound, endometrial lesions, real-time shear wave elastography, differential diagnosis

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored., (Copyright © 2024 American Society of Hematology.)

Seven new formononetin derivatives ( 1 - 7 ) were designed and prepared from formononetin (phase II phytoestrogen). The derivatives 9-butyl-3-(4-methoxyphenyl)-9,10-dihydro-4 H ,8 H -chromeno[8,7- e ][1,3]oxazin-4-one ( 2 ) and 9-(furan-3-ylmethyl)-3-(4-methoxyphenyl)-9,10-dihydro-4 H ,8 H -chromeno[8,7- e ][1,3]oxazin-4-one ( 7 ) promoted significant osteoblast formation by modulating the BMP/Smad pathway. Compound 7 exhibited potent antiosteoclastogenesis activity in RANKL-induced RAW264.7 cells and ovariectomy (OVX)-induced osteoporosis in mice by regulation of the RANK/RANKL/OPG pathway. Compound 7 regulated osteoblast and osteoclast simultaneously and showed better effect than the well-known drug ipriflavone in vivo , suggesting 7 as a patented antiosteoporosis candidate.

Objective: To analyze the trend of dementia mortality rate among individuals aged 60 to 94 years in China from 1982 to 2021. Methods: Utilizing data from the Global Burden of Disease Study 2021, the Joinpoint regression model was employed to analyze the trend in the dementia mortality rate among Chinese older adults from 1982 to 2021. The age-period-cohort analysis method was used to decompose the age effect, period effect and cohort effect of dementia mortality data in Chinese elderly people. Results: From 1982 to 2021, the crude mortality rate of dementia in elderly women aged 60-94 in China (133.67/100 000-214.02/100 000) was higher than that in men (70.92/100 000-119.70/100 000), and the age-standardized mortality rate of dementia in women (230.74/100 000-246.87/100 000) was also higher than that in men (132.88/100 000-140.19/100 000). The age-standardized mortality rate of dementia in both genders showed an N-shaped fluctuation trend. The average annual percent change (AAPC) of dementia mortality rate in elderly males aged 60-94 was 0.07% (95% CI : 0.01%-0.13%), and the AAPC of dementia mortality rate in elderly females was -0.01% (95% CI :-0.08%-0.07%). Age effect analysis showed that from the age of 60, the risk of dementia death in males and females increased with age, especially among elderly people aged 75-94 who experienced a rapid increase in dementia mortality rate. The period effect analysis showed that the overall risk of dementia death in elderly men and women aged 60-94 was decreasing, but it had increased from 2017 to 2021. The cohort effect analysis showed that the risk of dementia death was lower in later birth cohorts. Conclusion: From 1982 to 2021, the dementia mortality rate among Chinese older adults aged 60 to 94 years exhibited fluctuations. Particularly, there has been a notable rebound in recent years. Special attention should be directed towards female seniors and those aged 75 to 94 years.

The potato planting area of Guizhou Province ranks second in China. However, due to factors such as climatic conditions and unbalanced fertilization, soil organic matter in potato fields is consumed rapidly and has a large deficit, which affects soil biological function and soil fertility. Biochar and organic fertilizer are effective ways to supplement foreign aid organic matter to improve soil quality. However, the differences in soil fertility and microbial community structure and their relationships under the conditions of organic fertilizer or biochar combined with chemical fertilizer are not clear. In this study, three treatments of conventional fertilization （NPK）, increased application of biochar （NPKB）, and increased application of organic fertilizer （NPKO） were set up to investigate the characteristics of potato rhizosphere soil, bacterial community composition, and diversity； to analyze the effects of these factors on the soil integrated fertility index； and to explore the direct and indirect effects of IFI on soil fertility and bacterial community structure differences between treatments and their driving factors. The results showed that soil pH, available phosphorus （AP）, available potassium （AK）, total nitrogen （TN）, organic carbon （SOC）, and C/N ratio were significantly higher in the NPKB and NPKO treatments than in the NPK treatment （ P <0.05）. Soil IFI was greatest for NPKO, followed by NPKB and least for the NPK treatment. A total of 8 214 ASVs were obtained from all the soil samples, belonging to 26 phyla, 75 classes, 165 orders, 176 families, and 251 genera （excluding unidentified fungi）. Proteobacteria, Actinobacteria, and Chloroflexi were the dominant phyla, accounting for 54.85% of all ASVs. Compared to that in the NPK and NPKB treatments, the NPKO treatment had the highest bacterial diversity and number of significantly different taxa, and soil AN, AP, AK, SOC, TN, and IFI were significant correlates of bacterial diversity index （ P <0.05）. Additionally, pH, TN, and SOC were significant influencers of bacterial taxa differences （ P <0.05）, with importance ranked as TN （70.59%） &gt; SOC （49.42%） &gt; pH （27.08%）. Structural equations suggested that pH-related soil properties and bacterial community diversity were the direct pathways influencing IFI, and soil pH-related soil characteristics could also indirectly affect IFI by affecting bacterial Shannon diversity. These results indicate that soil fertility and bacterial community structure were significantly different and correlated between the biochar and organic fertilizer addition treatments and that pH and bacterial community diversity were the key factors influencing IFI, with the NPKO treatment in particular having the best effect on improving IFI. Considering the effect of soil fertilization and the functional group of bacteria, NPKO is the recommended combination for the best synergistic effect of soil fertilization, that is, N 150 kg·hm -2 +P 2 O 5 135 kg·hm -2 +K 2 O 135 kg·hm -2 +organic fertilizer 6.6 t·hm -2 .

Competing Interests: Declaration of competing interest The authors declare no conflict of interest.

To explore the effect and mechanism of Gegen Qinlian Decoction(GQD) in inhibiting M1 polarization of macrophages under inflammatory hypoxia by simulating intestinal hypoxia microenvironment in vitro. A tri-gas incubator was used to simulate normal physiological hypoxia of the colon and inflammatory hypoxia microenvironments of ulcerative colitis(UC). RAW264.7 macrophages were divided into 18.5% O&#95;(2 )(normoxia group), 4% O&#95;2(physiological hypoxia group), and 1% O&#95;2(inflammatory hypoxia group), and they were induced by lipopolysaccharide(LPS) for 24 h. M1 polarization was detected by flow cytometry. Under the condition of 1% inflammatory hypoxia, they were divided into blank group, model group, and GQD-containing serum low, medium, and high dose groups. Flow cytometry was used to detect M1 polarization marker CD86, and ELISA was used to detect the expression of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in cell supernatant. The mRNA expression of hypoxia-inducible factor-1α(HIF-1α), TNF-α, and IL-1β was detected by qRT-PCR. Western blot was used to detect the expression of HIF-1α/nuclear transcription factor-κB(NF-κB) signaling pathway-related proteins. The nuclear translocation of NF-κB p65 was detected by immunofluorescence. The results showed that the positive rate of CD86 in the 1% O&#95;2 group was the highest. Under the condition of 1% inflammatory hypoxia, compared with the blank group, the expression of CD86, TNF-α, IL-1β, and HIF-1α in the model group increased. Compared with the model group, each group of GQD could reduce the expression of CD86, TNF-α, IL-1β, and HIF-1α. Compared with the blank group, the protein expression of HIF-1α, NF-κB p65, p-IKKα/β, and p-IκBα in the model group increased. Compared with the model group, the protein expression of HIF-1α, NF-κB p65, p-IKKα/β, and p-IκBα in GQD groups was significantly decreased. Compared with the blank group, NF-κB p65 in the model group entered the nucleus significantly. Compared with the model group, the nuclear expression of NF-κB p65 was decreased in each GQD group. Studies have shown that GQD may protect the intestine by down-regulating the HIF-1α/NF-κB signaling pathway to inhibit M1 polarization of macrophages and secretion of related inflammatory factors under 1% inflammatory hypoxia.

Mussel byssal proteins are of biomimetic importance for the development of novel underwater bio-adhesive agents. It is important to maintain a reduced state during the process of byssus adhesion. There are 19 mussel foot proteins (MFPs) have been reported in previous studies, among which only MFP-6 had been confirmed as an antioxidant protein in mussel byssus due to the function of cysteines, and playing an essential role in the redox balance of mussel byssus during adhesion process. Although the other four MFPs (MFP-16 ~ MFP-19) also have abundant cysteines, their function is still unknown. In this study, a novel mussel foot protein, named MFP-20, was identified from Mytilus coruscus foot. The sequential features, expression profile, and function of recombinant MFP-20 were verified. The results showed that MFP-20 has more abundant cysteines than other MFPs, the relative expression of mfp-20 was upregulated in Fe 3+ stress and low pH seawater. In addition, different adhesive substrates induced significant changes of expression level of mfp-20. Furthermore, rMFP-20 showed strong antioxidant capacity in the DPPH assay, and the abundant cysteines in its sequence may play vital roles in the antioxidation activity. Our findings revealed the possible function of MFP-20 with a totally different sequence from the reported MFP-6 and provided new clues for exploring the redox balance of mussel byssus during the adhesion process., 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. Published by Elsevier B.V.)

The mapping of long-wavelength phonons is important to understand and manipulate the thermal transport in multilayered structures, but it remains a long-standing challenge due to the collective behaviors of phonons. In this study, an experimental demonstration of mapping the long-wavelength phonons in an alloyed Al 0.1 Ga 0.9 As/Al 0.9 Ga 0.1 As superlattice system is reported. Multiple strategies to filter out the short- to mid-wavelength phonons are used. The phonon mean-free-path-dependent thermal transport properties directly demonstrate both the suppression effect of the ErAs nanoislands and the contribution of long-wavelength phonons. The contribution from phonons with mean free path longer than 1 μm is clearly demonstrated. A model based on the Boltzmann transport equation is proposed to calculate and describe the thermal transport properties, which depicts a clear physical picture of the transport mechanisms. This method can be extended to map different wavelength phonons and become a universal strategy to explore their thermal transport in various application scenarios.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear., Objectives: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE., Materials and Methods: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE., Results: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE., Conclusion: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations., (© 2023 John Wiley & Sons, Ltd.)

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-Exo LaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-Exo LaIMTS show obvious differences. The AnCar-Exo LaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-Exo LaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-Exo LaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Introduction: The mucosa-associated microbiota (MAM) is not as frequently studied in diarrhea-predominant irritable bowel syndrome (IBS-D) compared with the fecal microbiota. In this study, we examined the MAM in the terminal ileum and its correlation with bowel symptoms in IBS-D., Methods: Mucosal biopsies of the terminal ileum from 25 patients with IBS-D and 25 healthy controls were collected for 16S ribosomal RNA gene sequencing. Correlation analysis was performed., Results: Compared with healthy controls, the MAM in the terminal ileum showed a decreased alpha diversity in the IBS-D cohort (Chao1 and Shannon indexes, P < 0.05). And the overall MAM profile clustered separately into 2 groups (ADONIS [PERMANOVA, permutational multivariate analysis of variance], P < 0.05). At the phylum level, the relative abundance of Proteobacteria was significantly higher in the ileal MAM of patients with IBS-D while that of Firmicutes was significantly lower. At the genus level, the relative abundance of Pseudomonas was significantly higher in the IBS-D cohort, with lower Bacteroides and Ruminococcus . Moreover, 40.0% of patients with IBS-D had multiple small nodules (nodular lymphoid hyperplasia) on the mucosal surface of the terminal ileum, which indicated a low-grade inflammation. In patients with IBS-D with nodular lymphoid hyperplasia, the changes of Pseudomonas and Bacteroides were more overt. Correlation analysis revealed that the relative abundance of Pseudomonas positively correlated with abdominal pain and the severity of IBS., Discussion: Patients with IBS-D showed a dysbiosis of MAM in the terminal ileum, which may be associated with bowel symptoms. Moreover, 40.0% of them displayed mucosal low-grade inflammation, with a more severe mucosal microbial disturbance., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

A phytochemical investigation of Selaginella tamariscina led to the isolation of 17 selaginellin derivatives. Their inhibitory activities against breast cancer cells were screened, and preliminary structure-activity relationships were also established. Among them, dimeric selaginellin 17 showed potential activity against MDA-MB-231 cells with an IC 50 value of 3.2 ± 0.1 μM, corresponding to 4-fold higher potency than the reference compound 5-FU (IC 50 14.8 ± 0.2 μM). Mechanistic studies indicated that 17 could cause G2/M phase arrest in MDA-MB-231 cells and induce apoptosis accompanied by increased ROS levels., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Selaginellin derivatives induce apoptosis and G2/M phase arrest in breast cancer cells from Selaginella tamariscina”., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Leukemia encompasses a group of highly heterogeneous diseases that pose a serious threat to human health. The long-term outcome of patients with leukemia still needs to be improved and new effective therapeutic strategies continue to be an unmet clinical need. Shikonin (SHK) is a naphthoquinone derivative that shows multiple biological function includes anti-tumor, anti-inflammatory, and anti-allergic effects. Numerous studies have reported the anti-leukemia activity of SHK during the last 3 decades and there are studies showing that SHK is particularly effective towards various leukemia cells compared to solid tumors. In this review, we will discuss the anti-leukemia effect of SHK and summarize the underlying mechanisms. Therefore, SHK may be a promising agent to be developed as an anti-leukemia drug., 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 Dong, Chang, Gao, Zhang, Yan, Wu and Wang.)

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.

Dysregulated apoptosis and proliferation are fundamental properties of cancer, and microRNAs (miRNA) are critical regulators of these processes. Loss of miR-15a/16-1 at chromosome 13q14 is the most common genomic aberration in chronic lymphocytic leukemia (CLL). Correspondingly, the deletion of either murine miR-15a/16-1 or miR-15b/16-2 locus in mice is linked to B cell lymphoproliferative malignancies. However, unexpectedly, when both miR-15/16 clusters are eliminated, most double knockout (DKO) mice develop acute myeloid leukemia (AML). Moreover, in patients with CLL, significantly reduced expression of miR-15a, miR-15b, and miR-16 associates with progression of myelodysplastic syndrome to AML, as well as blast crisis in chronic myeloid leukemia. Thus, the miR-15/16 clusters have a biological relevance for myeloid neoplasms. Here, we demonstrate that the myeloproliferative phenotype in DKO mice correlates with an increase of hematopoietic stem and progenitor cells (HSPC) early in life. Using single-cell transcriptomic analyses, we presented the molecular underpinning of increased myeloid output in the HSPC of DKO mice with gene signatures suggestive of dysregulated hematopoiesis, metabolic activities, and cell cycle stages. Functionally, we found that multipotent progenitors (MPP) of DKO mice have increased self-renewing capacities and give rise to significantly more progeny in the granulocytic compartment. Moreover, a unique transcriptomic signature of DKO MPP correlates with poor outcome in patients with AML. Together, these data point to a unique regulatory role for miR-15/16 during the early stages of hematopoiesis and to a potentially useful biomarker for the pathogenesis of myeloid neoplasms.

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P&lt;0.05) and significant decreases in the levels of 11 substances(P&lt;0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P&lt;0.05) and up-regulated 10 biomarkers(P&lt;0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

Heart failure (HF) is a disease with high mortality and morbidity rate. Autophagy is critically implicated in HF progression. The current research was designed to investigate the function of Dioscin on oxidative stress, autophagy, and apoptosis in HF. In this study, doxorubicin (Dox) was employed to induce HF model and HL-1 cell damage model. Echocardiography implied that Dioscin could dramatically relieve heart function in vivo. Western blotting determined that Dioscin treatment reversed the promotive effect of autophagy caused by Dox through modulating levels of key autophagy-associated molecules, including Atg5 and Beclin1. Dioscin also impaired apoptosis by regulating apoptosis-related protein, including Bcl-2 and cleaved caspase-3 following Dox treatment in vivo and in vitro. Furthermore, the impacts of Dioscin were mediated by upregulation of PDK1-mediated Akt/mTOR signaling. The mTOR inhibitor (rapamycin) could counteract the therapeutic impact of Dioscin in vitro. Taken together, Dioscin could relieve cardiac function through blocking apoptosis and autophagy by activating the PDK1-elicited Akt/mTOR pathway., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

The health of the aquatic ecosystem has recently been severely affected by cyanobacterial blooms brought on by eutrophication. Therefore, it is critical to develop efficient and secure methods to control dangerous cyanobacteria, such as Microcystis aeruginosa. In this research, we tested the inhibition of M. aeruginosa growth by a Scenedesmus sp. strain isolated from a culture pond. Scenedesmus sp. culture filtrate that had been lyophilized was added to M. aeruginosa, and cultivation for seven days, the cell density, chlorophyll a (Chl-a) concentration, maximum quantum yield of photosystem II (Fv/Fm), the activities of superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde (MDA) and glutathione (GSH) were measured. Moreover, non-targeted metabolomics was carried out to provide light on the inhibitory mechanism in order to better understand the metabolic response. According to the results, M. aeruginosa is effectively inhibited by the lyophilized Scenedesmus sp. culture filtrate at a rate of 51.2%. Additionally, the lyophilized Scenedesmus sp. clearly inhibit the photosystem and damages the antioxidant defense system of M. aeruginosa cells, resulting in oxidative damage, which worsens membrane lipid peroxidation, according to changes in Chl-a, Fv/Fm, SOD, CAT enzyme activities and MDA, GSH. Metabolomics analysis revealed that the secondary metabolites of Scenedesmus sp. significantly interfere with the metabolism of M. aeruginosa involved in amino acid synthesis, membrane creation and oxidative stress, which is coherent with the morphology and physiology outcomes. These results demonstrate that the secondary metabolites of Scenedesmus sp. exert algal inhibition effect by breaked the membrane structure, destroyed the photosynthetic system of microalgae, inhibited amino acid synthesis, reduced antioxidant capacity, and eventually caused algal cell lysis and death. Our research provides a reliable basis for the biological control of cyanobacterial blooms on the one hand, and on other hand supply application of non-targeted metabolome on the study of microalgae allelochemicals., 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 Elsevier Ltd. All rights reserved.)

Lactate leads to the imbalance of mitochondria homeostasis, which then promotes vascular calcification. PARP1 can upregulate osteogenic genes and accelerate vascular calcification. However, the relationship among lactate, PARP1, and mitochondrial homeostasis is unclear. The present study aimed to explore the new molecular mechanism of lactate to promote VSMC calcification by evaluating PARP1 as a breakthrough molecule. A coculture model of VECs and VSMCs was established, and the model revealed that the glycolysis ability and lactate production of VECs were significantly enhanced after incubation in DOM. Osteogenic marker expression, calcium deposition, and apoptosis in VSMCs were decreased after lactate dehydrogenase A knockdown in VECs. Mechanistically, exogenous lactate increased the overall level of PARP and PARylation in VSMCs. PARP1 knockdown inhibited Drp1-mediated mitochondrial fission and partially restored PINK1/Parkin-mediated mitophagy, thereby reducing mitochondrial oxidative stress. Moreover, lactate induced the translocation of PARP1 from the nucleus to the mitochondria, which then combined with POLG and inhibited POLG-mediated mitochondrial DNA synthesis. This process led to the downregulation of mitochondria-encoded genes, disturbance of mitochondrial respiration, and inhibition of oxidative phosphorylation. The knockdown of PARP1 could partially reverse the damage of mitochondrial gene expression and function caused by lactate. Furthermore, UCP2 was upregulated by the PARP1/POLG signal, and UCP2 knockdown inhibited Drp1-mediated mitochondrial fission and partially recovered PINK1/Parkin-mediated mitophagy. Finally, UCP2 knockdown in VSMCs alleviated DOM-caused VSMC calcification in the coculture model. The study results thus suggest that upregulated PARP1 is involved in the mechanism through which lactate accelerates VSMC calcification partly via POLG/UCP2-caused unbalanced mitochondrial homeostasis., (© 2023. The Author(s).)

Endothelial injury and dysfunction contributes to atherosclerosis. LINC00346 plays a key role in vascular endothelial cell injury, however, the specific mechanism remains unclear. This study intends to further explore the relationship between LINC00346 and vascular endothelial injury. Circulating LINC00346 was significantly elevated in patients with coronary artery disease and had high diagnostic value for coronary artery disease. In cell experiments, we found that LINC00346 expression was significantly increased in the oxidized low-density lipoprotein (ox-LDL) intervention group, and LINC00346 knockdown delayed ox-LDL induced human umbilical vein endothelial cell (HUVEC) endothelial-to-mesenchymal transition. In addition, knockdown of LINC00346 mitigated ox-LDL-induced NOD-like receptor protein 1 (NLRP1)-mediated inflammasome formation and pyroptosis, but had no significant effect on NLRP3. By observing the number of autophagosome and detecting intracellular autophagic flux, we found that LINC00346 knockdown inhibited the ox-LDL-induced increase in intracellular autophagy level. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay were performed to confirm the inter-molecular interaction. LINC00346 acted as microRNA-637 sponge to up-regulate the expression of NLRP1. Up-regulation of microRNA-637 alleviated NLRP1-mediated pyroptosis in HUVEC and reduced intracellular autophagosome and autolysosome formation. Finally, we explored whether pyropotosis and autophagy interact with each other. We found that inhibition of intracellular autophagy could alleviate NLRP1-mediated pyroptosis. In conclusion, LINC00346 inhibited the activation of NLRP1-mediated pyroptosis and autophagy via binding to microRNA-637, therefore mitigating vascular endothelial injury., Competing Interests: Declaration of Competing Interest All authors declared that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the change of prevalence of malnutrition among Chinese primary and secondary school students and to analyze the policy effect during the period of the Program for the Development of Chinese Children 2011-2020 (PDCC 2011-2020)., Methods: The data of Chinese students aged 7 to 18 years were extracted from 8 successive cross-sectional surveys of the Chinese National Survey on Students ' Constitution and Health (CNSSCH) from 1985 to 2019. Malnutrition of students was evaluated according to the screening standard for malnutrition of school-age children and adolescents. The changes of prevalence of malnutrition among primary and secondary school students were described by gender, urban and rural areas, age group and province, from 2010 to 2019. The Joinpoint regression model was used to analyze the trajectory of the prevalence of malnutrition among students aged 7 to 18 years from 1985 to 2019, so as to evaluate the policy effect of the PDCC 2011-2020., Results: The prevalence of malnutrition among primary and secondary school students in China decreased from 12.7% in 2010 to 8.5% in 2019. The prevalence of malnutrition among boys and girls, urban and rural students, and students of all age groups showed a continuous downward trend ( P trend < 0.001) from 2010 to 2019. From 2010 to 2019, 27 of the 31 provinces (autonomous regions and municipalities) saw a significant decrease in the prevalence of malnutrition among primary and secondary school students. Joinpoint regression model showed that the prevalence of malnutrition among Chinese primary and secondary school students continued to decline from 1985 to 2019, but 2010 was the turning point in the downward trend. From 1985 to 2010, the prevalence of malnutrition among primary and secondary school students decreased by an average of 2.4% per year (95% CI : 1.9%-2.8%, P < 0.001), and the downward trend accelerated after 2010, with an average annual decline of 4.3% (95% CI : 2.4%-6.2%, P < 0.001)., Conclusion: The prevalence of malnutrition among primary and secondary school students in China continued to decline from 2010 to 2019, achieving the goal of controlling the prevalence of malnutrition among primary and secondary school students in the PDCC 2011-2020. The PDCC 2011-2020 may have played an important role in improving the malnutrition among primary and secondary school students. However, the problem of malnutrition among primary and secondary school students still exists, and it is still necessary to adhere to the coverage and financial support of the nutrition improvement plan in areas with high incidence of malnutrition.

Background/aims: Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy. Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD)., Methods: Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire)., Results: The MPR values for ZZKZ were significantly higher than those for doxepin ( P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma ( P < 0.001). The MPR values were negatively correlated with post-treatment stigma scores in both groups ( P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups., Conclusion: ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810)., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Phytochemical study on the whole plants of a Gentianaceous medicinal plant, Canscora lucidissima, gave one new acylated iridoid glucoside, canscorin A (1), and two new xanthone glycosides (2 and 3) together with 17 known compounds including five xanthones, eight xanthone glycosides, two benzophenone glucosides, caffeic acid, and loganic acid. Canscorin A (1) was assigned as a loganic acid derivative having a hydroxyterephthalic acid moiety by spectroscopic analysis together with chemical evidence, while 2 and 3 were elucidated to be a rutinosylxanthone and a glucosylxanthone, respectively. The absolute configurations of the sugar moieties of 2 and 3 were determined by HPLC analysis. The isolated compounds were evaluated for their inhibitory activities against erastin-induced ferroptosis on human hepatoma Hep3B cells and LPS-stimulated IL-1β production from murine microglial cells., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy., (© 2023. The Author(s).)

Microbes have evolved multiple mechanisms to resist environmental stresses, which are regulated in complex and delicate ways. Though the role of cell membranes in acid resistance from the perspective of physicochemical properties and membrane proteins has been deeply studied, the function of eisosomes is still in its infancy. In this study, we firstly reported the dynamic changes of eisosomes under acid stress and the decreased acid tolerance of yeasts caused by eisosome disruption. Physiological indicators and non-targeted lipid profiling revealed that eisosome disruption caused changes in multiple lipids and imbalances in lipid homeostasis, which are responsible for membrane integrity damage. Thus the increased infiltration of carboxylic acids and the raised ROS levels were detected in strains with disrupted eisosome assembly, resulting in decreased cellular tolerance. The results here provide novel insights into the acid-resistant mechanism of yeasts from the perspective of the cell membrane subdomain, which has practical impacts on green biological manufacturing and food preservation., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and trigger an inflammatory response via the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways. Lindenane type sesquiterpene dimers (LSDs) are characteristic metabolites of plants belonging to the genus Sarcandra (Chloranthaceae). The aim of this study was to evaluate the potential anti-inflammatory effects of the LSDs shizukaol D (1) and sarcandrolide E (2) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages in vitro, and explore the underlying mechanisms. Both LSDs neutralized the LPS-induced morphological changes and production of nitric oxide (NO), as determined by CCK-8 assay and Griess assay, respectively. Furthermore, shizukaol D (1) and sarcandrolide E (2) downregulated interferon β (IFNβ), tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) mRNA levels as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibited the phosphorylation of nuclear factor kappa B p65 (p65), nuclear factor kappa-Bα (IκBα), Jun N-terminal kinase (JNK), extracellular regulated kinase (ERK), mitogen-activated protein kinase p38 (p38), MyD88, IL-1RI-associated protein kinase 1 (IRAK1), and transforming growth factor-β-activated kinase 1 (TAK1) proteins in the Western blotting assay. In conclusion, LSDs can alleviate the inflammatory response by inhibiting the TLR/MyD88 signalling pathway., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Mytilus coruscus is a dominant shellfish in the Yangtze estuary and its adjacent sea area. Food deprivation often occurs during their growth due to fluctuations in algal abundance caused by seasonal freshwater flushing and high-density aquaculture mode. To investigate the coping strategies of M. coruscus to starvation stress, electron microscopy and differential proteomic analysis were performed on the critical feeding organ gill of the mussels after 9 days of starvation. The electron microscopy results showed that the cilia of the mussel gills were dissolved, and the gaps between gill filaments widened under starvation. Differential proteomic analysis revealed that phagocytosis-related proteins such as ATPeV1E, ATPeV1C, LAMP1&#95;2 and CTSL were significantly upregulated, and the phagocytosis pathway was significantly enriched ( p < 0.05). In addition, the corin content in gill and myeloperoxidase level as well as the number of dead cells in blood were both significantly increased ( p < 0.05). What's more, proteomic data suggested that immune maintenance, cellular transport and metabolism related pathways were significantly enriched, which illustrated an immune and metabolism responses under starvation. This study reveals for the first time that phagocytosis functions as an essential strategy for M. coruscus to cope with starvation, which provides new scientific knowledge and a theoretical basis for understanding the adaptation mechanisms of mussel to starvation and for rational optimization of mussel culture patterns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Li, Zhang, Chen, Sun, Gu, Huang, He, Qi, Guo, Liao and Yan.)

Objective: Through the use of high-density polyethylene implants in adults with cleft lip and palate nasal deformities and abnormal functions, to evaluate the clinical effect of postoperative patients on improving nasal shape and symptoms. Methods: A retrospective study of 12 patients with nasal deformities after cleft lip and palate surgery in the Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine from January 2018 to January 2022 was completed, including 7 males and 5 females, with the age ranging from 18 to 29 years. All the patients underwent nasal deformity correction, and nasal septum correction was performed if necessary. High-density polyethylene implants (MEDPOR/Su-Por) were used intraoperatively. Follow-up for at least 6 months was performed to measure the relevant appearance indicators and subjective Visual Analog Scale (VAS) scores, and to compare the clinical effects before and after surgery. SPSS 22.0 software was used for statistical analysis. Results: Before and after surgery, the average VAS score of nasal obstruction decreased by (4.83±0.94) points; the average VAS score of appearance satisfaction increased by (3.92±1.08) points; the height of nasal columella was increased by (1.79±0.78)mm; the height of nasal tip was increased by (2.79±1.50)mm; the height of ipsilateral nostril was increased by (1.83±0.62)mm; the width of the ipsilateral nasal floor was reduced by (0.42±0.47)mm. All of above were statistically significant (all P <0.05). Conclusion: High-density polyethylene implants can effectively improve the shape and function of the nose in operations related to cleft lip and palate nasal deformity and abnormal functions, and are an ideal synthetic material.

Objective: The Coronavirus Disease 2019 (COVID-19) has brought severe damage to global health and socioeconomics. In China, traditional Chinese medicine (TCM) is the most important complementary and alternative medicine (CAM) and it has shown a beneficial role in the prevention and treatment of COVID-19. However, it is unknown whether patients are willing to accept TCM treatment. The objective of our study is to investigate the acceptance, attitude, and independent predictors of TCM among asymptomatic COVID-19 patients admitted to Shanghai fangcang hospital during the outbreak of the COVID-19 pandemic in Shanghai in 2022., Methods: A cross-sectional study was conducted on asymptomatic COVID-19 patients in the largest fangcang hospital in Shanghai, China, from April 22, 2022, to May 25, 2022. Based on the literature review of previous similar studies, a self-report questionnaire was developed to assess the patients' attitude and acceptance of TCM, and a multivariate logistic regression analysis was conducted to determine the independent predictors of TCM acceptance., Results: A total of 1,121 patients completed the survey, of whom 91.35% were willing to accept CAM treatment whereas 8.65% of participants showed no willingness. Multivariate logistic regression analysis revealed that the patients who have received two doses of COVID-19 vaccine (OR = 2.069, 95%CI: 1.029-4.162, P = 0.041 vs. not received), understood the culture of TCM (OR = 2.293, 95%CI: 1.029-4.162, P = 0.014 vs. not understood), thought the TCM treatment is safe (OR = 2.856, 95%CI: 1.334-6.112, P = 0.007 vs. not thought), thought the TCM treatment is effective (OR = 2.724, 95%CI: 1.249-5.940, P = 0.012 vs. not thought), and those who informed their attending physician if using TCM for treatment (OR = 3.455, 95%CI:1.867-6.392, P < 0.001 vs. not informed) were more likely to accept TCM treatment. However, patients who thought TCM might delay your treatment (OR = 0.256, 95%CI: 0.142-0.462, P < 0.001 not thought) was an independent predictor for unwillingness to accept TCM treatment., Conclusion: This study preliminarily investigated the acceptance, attitude, and predictors of intention to receive TCM among asymptomatic COVID-19 patients. It is recommended to increase the publicity of TCM, clarify the impact of TCM and communicate with attending doctors that meet the healthcare needs of asymptomatic COVID-19 patients., (© 2023. The Author(s).)

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated., Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD., Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p  < 0.001) had worse outcome., Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment., Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding., Competing Interests: D.C.F. has received research funding and consulting fees from EUSA Pharma. The remaining authors declare no competing financial interests., (© 2023 Published by Elsevier Ltd.)

Introduction: The leukemic cells of patients with chronic lymphocytic leukemia (CLL) are often unique, expressing remarkably similar IGHV-IGHD-IGHJ gene rearrangements, "stereotyped BCRs". The B-cell receptors (BCRs) on CLL cells are also distinctive in often deriving from autoreactive B lymphocytes, leading to the assumption of a defect in immune tolerance., Results: Using bulk and single-cell immunoglobulin heavy and light chain variable domain sequencing, we enumerated CLL stereotype-like IGHV-IGHD-IGHJ sequences (CLL-SLS) in B cells from cord blood (CB) and adult peripheral blood (PBMC) and bone marrow (BM of healthy donors. CLL-SLS were found at similar frequencies among CB, BM, and PBMC, suggesting that age does not influence CLL-SLS levels. Moreover, the frequencies of CLL-SLS did not differ among B lymphocytes in the BM at early stages of development, and only re-circulating marginal zone B cells contained significantly higher CLL-SLS frequencies than other mature B-cell subpopulations. Although we identified CLL-SLS corresponding to most of the CLL major stereotyped subsets, CLL-SLS frequencies did not correlate with those found in patients. Interestingly, in CB samples, half of the CLL-SLS identified were attributed to two IGHV-mutated subsets. We also found satellite CLL-SLS among the same normal samples, and they were also enriched in naïve B cells but unexpectedly, these were ~10-fold higher than standard CLL-SLS. In general, IGHV-mutated CLL-SLS subsets were enriched among antigen-experienced B-cell subpopulations, and IGHV-unmutated CLL-SLS were found mostly in antigen-inexperienced B cells. Nevertheless, CLL-SLS with an IGHV-mutation status matching that of CLL clones varied among the normal B-cell subpopulations, suggesting that specific CLL-SLS could originate from distinct subpopulations of normal B cells. Lastly, using single-cell DNA sequencing, we identified paired IGH and IGL rearrangements in normal B lymphocytes resembling those of stereotyped BCRs in CLL, although some differed from those in patients based on IG isotype or somatic mutation., Discussion: CLL-SLS are present in normal B-lymphocyte populations at all stages of development. Thus, despite their autoreactive profile they are not deleted by central tolerance mechanisms, possibly because the level of autoreactivity is not registered as dangerous by deletion mechanisms or because editing of L-chain variable genes occurred which our experimental approach could not identify., 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 Vergani, Bagnara, Agathangelidis, Ng, Ferrer, Mazzarello, Palacios, Yancopoulos, Yan, Barrientos, Rai, Stamatopoulos and Chiorazzi.)