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Background: As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics were approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial., Methods: The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis., Results: Our study showed that thyroid gland disorders had the strongest signal in children. Patients aged 12-18 and treatment with minocycline are risk factors for thyroid adverse events (12-18: OR = 10.727 [7.113-16.177], p  < 0.0001; minocycline: OR = 17.025 [10.475-27.678], p < 0.0001). Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia was primarily reported with tigecycline and eravacycline., Conclusion: This study provided basic evidence for further research on tetracyclines-related adverse events. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.

Three new compounds 1-glyceryl 9( β ), 10( α ), 11( β )-trihydroxy-12( Z )-octadecenoate, 2' S -20- O - p -hydroxyphenylpropionyloxy-20-hyd-roxyarachidic acid glycerol ester ( 2 ), 3- O - α -l-arabinopyranosyl-(1→6)- β -d-glucopyranoside of ethyl (3 S )-hydroxybutanoate ( 3 ), as well as a new natural product ( 4 ) were isolated from the fruits of Solanum virginianum L. The structures of 26 compounds were determined by comprehensive spectroscopic analyses, NMR calculation, chemical methods, and comparisons of spectroscopic data. Compounds 2 and 16 exhibited good anti-inflammatory activity in the LPS-induced RAW 264.7 inflammatory model with IC 50 values of 16.75 ± 1.54 and 22.43 ± 2.01  μ M, respectively.

Objective: The effects of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-exos) on serum metabolites and intestinal microbiota in rats after liver trauma were discussed., Methods: Adult Wistar Albino rats were assigned into control, model (liver trauma), MSCs, and MSC-exos groups (n = 6). The study examined changes in the inflammatory environment in liver tissues were analyzed by histological examination and analysis of macrophage phenotypes. Alterations in serum metabolites were determined by untargeted metabonomics, and gut microbiota composition was characterized by 16S rDNA sequencing. Correlations between specific gut microbiota, metabolites, and inflammatory response were calculated using Spearman correlation analysis., Results: Rats with liver trauma after MSCs and MSC-exos treatment exhibited attenuated inflammatory infiltration and necrosis in liver tissues. MSCs and MSC-exos treatment reduced the proportion of M1 macrophages, accompanied by a decrease in inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) levels. Furthermore, MSCs and MSC-exos treatment expanded the proportion of M2 macrophages, accompanied by an increase in arginase-1 (Arg-1) and interleukin-10 (IL-10) levels. The beneficial effects of MSC-exo treatment on rats with liver trauma were superior to those of MSC treatment. The composition and abundance of the gut microbiota and metabolites were altered in pathological rats, whereas MSC and MSC-exo intervention partially restored specific gut microbiota and metabolite alterations. At the phylum level, alterations in Bacteroidota, Proteobacteria, and Verrucomicrobiota were observed after MSC and MSC-exo intervention. At the genus level, Intestinimonas, Alistipes, Aerococcus, Faecalibaculum, and Lachnospiraceae&#95;ND3007&#95;group were the main differential microbiota. 6-Methylnicotinamide, N-Methylnicotinamide, Glutathione, oxidized, ISOBUTYRATE, ASCORBATE, EICOSAPENTAENOATE, GLYCEROL 3-PHOSPHATE, and Ascorbate radical were selected as important differential metabolites. There was a clear correlation between Ascorbate, Intestinimonas/Faecalibaculum and inflammatory cytokines., Conclusion: MSC-exos promoted the repair of tissue damage in rats with liver trauma by regulating serum metabolites and intestinal microbiota, providing new insights into how MSC-exos reduced inflammation in rats with liver trauma., 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 Ltd.. All rights reserved.)

A phytochemical investigation on the 70% EtOH extract of the fruit of Acanthpanax senticosu s resulted in the isolation of three new triterpenoids, Falcatane C ( 1 ), Acasentrioid F ( 2 ), Acasentrioid G ( 3 ) together with twenty-seven known ones ( 4 - 30 ). Structural elucidation of all the compounds was performed by spectral methods such as 1D or 2D ( 1 H- 1 H COSY, HSQC, and HMBC), NMR spectroscopy, and high-resolution mass spectrometry. Moreover, all compounds were evaluated for their effects on H 2 O 2 -induced neurotoxicity in human neuroblastoma SH-SY5Ycells. Compounds 13 and 15 showed significant neuroprotective impact at a specific concentration, and compounds 1 , 3 , 5 , 9 , 11 , 13-15 , 17 , 20-21 , 23-25 , 27 , 29-30 showed moderate neuroprotective effect. The current study suggests that triterpenes in Eleutherococcus senticosus (Rupr.) Harms may play an essential role in the neuroprotective properties.

Objectives: To explore the therapeutic effect of Fu's subcutaneous needling at myofascial trigger points (MTrPs) on pain, lumbar mobility and the quality of life in patients with lumbar disc herniation (LDH), so as to provide clinicians with new ideas and methods in treating LDH., Methods: One hundred patients with LDH admitted to department of rehabilitation medicine of the affiliated hospital of Chengdu University of Traditional Chinese Medicine from January 2022 to January 2023 were collected as the subjects, and they were randomly divided into an observation group and a control group, 50 cases in each one. In the observation group, the spreading technique of Fu's subcutaneous needling was delivered at MTrP. In the control group, the routine acupuncture was applied to Shenshu (BL23), Weizhong (BL40) and MTrP. The treatment was given 3 times weekly, for 2 weeks in the two groups. The score of visual analogue scale (VAS) was evaluated before treatment, at the moment after the 1 st treatment completion and after 2 weeks of treatment, separately, and the inclinometer was adopted to measure the range of motion (ROM) of the lumbar flexion, extension and lateral flexion. The numbers of MTrPs and their distribution were recorded before treatment and after the completion of a 2-week treatment in the two groups. Before treatment and in 4 weeks of follow-up, using SF-36 scale, the score of the quality of life was evaluated. The incidence of adverse effects was recorded., Results: At the moment of the 1 st treatment completion and after 2 weeks of treatment, VAS score and ROM of the lumbar region were significantly improved in comparison with those before treatment in the two groups and the improvement was superior in the observation group compared with the control group ( P <0.05, P <0.01). After 2 weeks of treatment, the total number of MTrPs and the counts of MTrPs in each muscle zone were reduced when compared with those before treatment ( P <0.05). In the observation group, the total number of MTrPs and numbers of MTrPs in the zones of quadratus lumborum, musculi multifidus and musculi iliocostalis lumborum decreased significantly when compared with the control group ( P< 0.05), while the difference was not significant in the numbers in the zone of musculi glutaeus medius between the two groups. In 4 weeks of follow-up, the scores of SF-36 scale were improved in comparison with those before treatment in each group and the result in the observation was better ( P <0.05). No any adverse events occurred during treatment in the two groups., Conclusions: Fu's subcutaneous needling is effective for reducing the numbers of MTrPs and improving analgesia, ROM of the lumbar region, as well as the long-term quality of life in the patients with LDH.

Nine compounds were isolated and identified from ethanolic extracts of Saposhnikovia divaricata , including one new alkaloid ( 1 ), one new pentacyclic triterpenoid ( 9 ), and seven known alkaloids ( 2 - 8 ). Structural elucidation of compounds 1 and 9 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for antiproliferative activity against two cancer cell lines (LN229, A549) in vitro . Compounds ( 1 - 9 ) showed no significant antiproliferative activity., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Three new steroids (1-3) and 13 reported analogs (4-16) were extracted from Datura metel L. pericarps. Structure analysis of these extracted compounds was performed by 1 D-NMR and 2 D-NMR spectroscopy, and their spectra were compared with those of similar compounds previously described in the literature. The extracted steroids (1-3) and known compounds (4-16) were evaluated for anti-inflammatory activity against LPS-activated RAW 264.7 cells. Compounds 5 , 7 , 9 , 12 and 15 showed potential anti-inflammatory activity with IC 50 less than 35 μM, while compounds 3 and 11 showed weak anti-inflammatory activity with IC 50 less than 100 μM.

Four new sesquiterpenoids, dstramonins A-D ( 1-4 ), and one new natural product ( 5 ), together with three known compounds ( 6-8 ), were isolated from the leaves of Datura stramonium L. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the literature. The cytotoxicity of isolates against LN229 cells was assessed and compounds 2 - 4 , and 7 displayed cytotoxic activity with IC 50 values ranging from 8.03 to 13.83  μ M.

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC 50 values of 2.75 ± 0.86 and 3.78 ± 0.50 μM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

Two novel phenylpropanoid amides, namely huomarenamide A ( 1 ) and huomarenamide B ( 2 ), along with twelve known compounds ( 3 - 14 ), were isolated from the seeds of Cannabis sativa L. The structures with absolute configurations of new compounds were unequivocally determined by spectroscopic analyses and the ECD method. The identification of the known compounds was based on a comparison of their 1D NMR data with literature references. All compounds were assessed for cytotoxic activity against LN229 cells, revealing that compounds 2 , 13 , and 14 exhibited significant cytotoxicity with IC 50 values ranging from 9.02 to 21.26 μM.

Phytochemical investigation of the roots of Saposhnikovia divaricata (Turcz.) Schischk resulted in the isolation of twelve coumarin derivatives including one new 3,4-dihydroisocoumarin ( 1 ) and eleven known 3,4-unsubstituted coumarins ( 2-12 ). Structural elucidation of compounds 1-12 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. LPS-induced RAW264.7 inflammatory cell model was used to determine the potential antiinflammation activity of all the isolated compounds in vitro . The results showed that compound 3 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages (IC 50 = 4.54 ± 1.71 μM), more active than the positive control (L-NMMA).

Introduction: Protein A immunoadsorption (IA) is proving to be an effective treatment method for autoimmune diseases and other disorders. Regional citrate anticoagulation (RCA) prevents clotting in extracorporeal circuits without increasing hemorrhage risk in high bleeding risk patients, but there are no specific guidelines for its application in IA. We aimed to evaluate the safety and adverse effects of RCA used in IA therapy., Methods: We conducted a retrospective cohort study of forty-five RCA-IA sessions in 14 HLA-incompatible kidney transplant recipients with focus on the safety and adverse effects of RCA in IA. The extracorporeal circuit was equipped with 4% trisodium citrate solution as an anticoagulant and 10% calcium gluconate solution to compensate for calcium loss. The adverse events, including coagulation and blood biochemical indexes, especially calcium level, were recorded., Results: Our study found that 93.33% of the sessions were without circuit clotting or other significant complications. A slight decrease in fibrinogen level was observed, but without significant variations in other coagulation indexes or platelet count. There was a slight elevation in the potential of hydrogen, bicarbonate, and base excess after 2 h and 6 h posttreatment relative to prior treatment, but these returned to normal levels within 24 h posttreatment., Conclusion: RCA is a feasible, effective, and safe anticoagulation option for IA treatment in HLA-incompatible kidney transplant recipients. Electrolyte disturbances, especially alkalosis, hypocalcemia, hypomagnesemia, and fluid status, should be closely monitored and managed., Competing Interests: The authors declare that there were no conflicts of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Two new compounds ( 1 and 2 ), along with thirty-one known compounds ( 3 - 33 ) were isolated from the fruits of Solanum xanthocarpum . The structure of isolates was elucidated by analysis of spectroscopic data and the physicochemical methods. Meanwhile, the anti-inflammatory activity of isolates was determined using LPS-induced RAW 264.7 cells. The results of anti-inflammatory assays indicated that most isolated compounds ( 3, 4 , 6 , 8 - 14 , 17-20 , and 30 ) possessed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 cells with IC 50 values ranging from 14.33 to 48.55  μ M.

Six novel withanolides, along with nine known related compounds were isolated from the leaves of Datura stramonium L. The structures and absolute configurations of the new withanolides were elucidated by employing various spectral techniques and comparing them with those previously reported in the literature. In addition, four withanlides demonstrated interesting cytotoxic activity on LN229 cells with IC 50 <20 μM., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Two new quinoline alkaloids ( 1 - 2 ) together with twenty-two known alkaloids ( 3 - 24 ) were isolated and identified from Dictamnus dasycarpus Turcz. Compounds 6 - 7 , 9 , 11 , 15 - 16 , 19 and 24 were isolated from D. dasycarpus for the first time. The structures of all compounds were characterised by spectroscopic methods (1D, 2D NMR and HRESIMS). The anti-proliferative activity was mediated by the arrest of three human cancer cell lines (SW982, HepG2 and A549) of all the compounds that were evaluated by CCK-8 assay.

Objectives: Gefitinib (GEF) is a targeted medicine used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). However, GEF's hepatotoxicity limits its clinical use. This study aims to investigate the protective effect of naringin (NG) against GEF-induced hepatotoxicity., Materials and Methods: Fifty female ICR mice were randomly divided into 5 groups: Control, GEF (200 mg/kg), NG (50 mg/kg) + GEF (200 mg/kg), NG (100 mg/kg) +GEF (200 mg/kg), NG (200 mg/kg) +GEF (200 mg/kg). After 4 weeks of continuous administration, the mice were euthanized. The blood and liver tissue samples were collected., Results: The results indicated that the GEF group showed increased liver index, liver enzyme activities, and decreased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Some hepatocytes showed hydropic degeneration and focal necrosis. Cell apoptosis, Cleaved-caspase3, and Poly (ADP-ribose) polymerase 1 (PARP1) increased. Transmission electron microscopy revealed the presence of numerous autophagic lysosomes or autophagosomes around the cell nucleus. Compared to the GEF group, NG can reverse these changes., Conclusion: In summary, NG alleviates GEF-induced hepatotoxicity by anti-oxidation, inhibiting cell apoptosis, and autophagy. Therefore, this study suggests the use of NG to mitigate GEF's toxicity to the liver., Competing Interests: The authors declare that they agree with the contents of the study and there are no financial interests to report.

Six new naphthoquinones, euchronin A-F (1-6) and nine known naphthoquinones (7-15), were isolated from the roots of Arnebia euchroma (Royle) Johnst. The structures of the new compounds were confirmed by extensive spectroscopic analyses, including UV, IR, HR-ESI-MS, 1D and 2D NMR. In the present study, we estimated the anti-proliferative activities of these compounds with HaCaT cells. The results indicated that compounds 2 and 4 showed strong anti-proliferative activities at 25 μM, with relative viability at 38.83% and 68.44%, respectively., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: Invasive lung adenocarcinoma (LUAD) patients with the micropapillary (MPP) component tend to have extremely poor prognosis. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on the prognosis of patients with the MPP component is necessary., Method: A total of 621 Chinese patients with surgically resected invasive LUAD who underwent genetic testing for lung cancer were enrolled in this retrospective study. The genomic profiling of major lung cancer-related genes based on next-generation sequencing (NGS) was carried out on formalin-fixed paraffin-embedded tumor samples., Result: Among 621 patients with invasive LUAD, 154 (24.8%, 154/621) had the MPP component. We found that PIK3CA (4.5% vs 1.3%), KRAS (9.1% vs 4.7%), and ROS1 (2.6% vs 0.4%) were more frequent in patients with the MPP component than those without the MPP component (P < 0.05). The co-mutation occurred in 66 patients (10.6%, 66/621), of which 19 patients with the MPP component. Most of them were EGFR co-mutations (89.5%, 17/19), including EGFR and PIK3CA, EGFR and ERBB2, and other types. Patients with the MPP component who harbored EGFR co-mutations showed significantly worse recurrence-free survival (RFS) than single EGFR mutation (median RFS 20.1 vs 30.5 months; hazard ratio [HR]: 8.008; 95% confidence interval [CI]: 1.322-48.508)., Conclusions: Patients with the MPP component harbored the co-mutation of driver genes had a higher risk of recurrence after surgery, especially in patients with EGFR co-mutation. EGFR co-mutation was a significant prognostic factor for RFS in patients with the MPP component., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

The ongoing coronavirus infectious disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still urgently requires effective treatments. The 3C-like (3CL) protease of SARS-CoV-2 is a highly conserved cysteine protease that plays an important role in the viral life cycle and host inflammation, providing an ideal target for developing broad-spectrum antiviral drugs. Herein, we describe the discovery of a large number of herbs mainly produced in Heilongjiang Province, China, that exhibited different inhibitory activities against SARS-CoV-2 3CL protease. We confirmed that Syringa reticulata , which is used for clinical treatment of chronic bronchitis and asthma, is a specific and potent inhibitor of 3CL protease. A 70 % ethanol extract of S. reticulata dose-dependently inhibited the cleavage activity of 3CL protease in a fluorescence resonance energy transfer assay with an IC 50 value of 0.0018 mg/mL, but had minimal effect in pseudovirus-based cell entry and luciferase-based RNA-dependent RNA polymerase assays. These results suggest that S. reticulata will be a potential leading candidate for COVID-19 treatment., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2023 The Authors.)

Three undescribed schinortriterpenoids, schinensilactones D-F ( 1-3 ), together with five known ones, namely, wuweizidilactone A ( 4 ), wuweizidilactone C ( 5 ), wuweizidilactone F ( 6 ), wuweizidilactone J ( 7 ) and wuweizidilactone N ( 8 ), were isolated from the leaves of Schisandra chinensis (Turcz.) Baill. The structures of new compounds were established by analysis of their spectroscopic data including MS, IR, 1D- and 2D-NMR spectra. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD) spectra. All compounds were evaluated for their neuroprotective effects against H 2 O 2 -induced injury in human neuroblastoma SH-SY5Y cell lines. Cell viability was remarkably reduced to 52.33% in H 2 O 2 -treated cells. Compounds 5 - 7 exhibited moderate neuroprotective activities at 50  μ M, with cell viability of 64.84%, 67.34% and 63.73%, respectively.

Eleven compounds were isolated and identified from ethanolic extracts of Solanum virginianum fruits, including two new compounds ( 1 - 2 ) and nine known compounds ( 3 - 11 ). Their structures were determined to be melongenaterpene C15- O - β -D-glucopyranoside ( 1 ), (9 Z )-3,7,11,15-tetramethyl -hexadeca-1,6,10-triene-3,5,14,15-tetraol-5- O - β -D-glucopyranoside ( 2 ), actini-dioionoside A ( 3 ), byzantionoside B ( 4 ), citroside A ( 5 ), 7Z-roseoside ( 6 ), matenoside A ( 7 ), megastigmane ( 8 ), dihydrophaseic acid 3'- O - β -D-glucopyranoside ( 9 ), taraxerol ( 10 ), and huzhangoside C ( 11 ). In this paper, NMR spectroscopy was used to study the structures of the compounds, comparing their data with those in the literature. In addition, the potential anti-inflammatory activity of the compounds was also evaluated using the RAW264.7 cell inflammation model induced by lipopolysaccharide (LPS). The terpenoids showed no significant anti-inflammatory activity., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP., Methods: Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis., Results: Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9-87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5-61) versus 57.5 years (range 9-87) ( P =0.03). The median time of symptom onset was 7 days (range 2-29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1-43), and the median time to relieve symptoms was 4 days (range 1-12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia., Conclusion: Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2023 Pan et al.)

The RNA-guided Cas9 endonuclease from Staphylococcus aureus (SauCas9) can catalyze multiple-turnover reactions whereas Cas9 from Streptococcus pyogenes (SpyCas9) is a single-turnover enzyme. Here we dissect the mechanism of multiple-turnover catalysis by SauCas9 and elucidate its molecular basis. We show that the multiple-turnover catalysis does not require more than stoichiometric RNA guides to Cas9 nuclease. Rather, the RNA-guide loaded ribonucleoprotein (RNP) is the reactive unity that is slowly released from product and recycled in the subsequent reaction. The mechanism that RNP is recycled for multiple-turnover reaction entails the unwinding of the RNA:DNA duplex in the R-loop. We argue that DNA rehybridization is required for RNP release by supplementing the energy cost in the process. Indeed, turnover is arrested when DNA rehybridization is suppressed. Further, under higher salt conditions, both SauCas9 and SpyCas9 showed increased turnover, and engineered SpyCas9 nucleases that form fewer direct or hydrogen bonding interactions with target DNA became multiple-turnover enzymes. Thus, these results indicate that for both SpyCas9 and SauCas9, turnover is determined by the energetic balance of the post-chemistry RNP-DNA interaction. Due to the conserved protein core folds, the mechanism underpinning turnover we establish here is likely operant in all Cas9 nucleases., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Phenylpropionamides in the seed of Cannabis sativa L. (PHS) have a protective effect on neuroinflammation and antioxidant activity. In this study, the UHPLC-Orbitrap-fusion-TMS-based metabolomics approach was used to analyze the serum samples and identify potential biomarkers in Streptozotocin (STZ) induced Alzheimer's disease (AD) rats. The results revealed that primary bile acid biosynthesis and taurine and hypotaurine metabolism were significantly correlated with STZ-induced AD rats. In addition, the key enzymes in these two pathways were verified at the protein level. The levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD), cysteamine (2-aminoethanethiol) dioxygenase (ADO), 7α-hydroxylase (CYP7A1), and sterol 12α-hydroxylase (CYP8B1) were the key enzymes affecting the two pathways in AD rats compared with the control group (CON). Furthermore, after a high-dose group of phenylpropionamides in the seed of Cannabis sativa L. (PHS-H) was administrated, the levels of CDO1, CSAD, CYP7A1, and CYP8B1 were all callback. These findings demonstrate for the first time that the anti-AD effect of PHS is associated with the regulation of primary bile acid biosynthesis and taurine and hypotaurine metabolism in STZ-induced AD rats., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

To describe the characteristics of multiple myeloma (MM) by retrospectively analyzing data from patients with MM in hematology, nephrology, and orthopedic departments, we selected inpatients diagnosed with MM for the first time who were admitted to the hematology department of Taizhou Hospital of Zhejiang Province between January 1, 2017, and June 30, 2021 ([Formula: see text]) and those admitted to the nephrology ([Formula: see text]) and orthopedic ([Formula: see text]) departments of Taizhou Hospital of Zhejiang Province between January 1, 2010, and June 30, 2021. For patients with MM initially diagnosed in the nephrology or orthopedic departments, age- and sex-matched patients without MM were randomly selected in a 1:1 ratio. Conditional logistic regression models were used to assess the risk of MM in hospitalized patients in the nephrology and orthopedic departments. This study included 200 patients, with a median age of 65 years. There were differences among patients in the three departments with respect to fracture, degree of anemia, proteinuria levels, red blood cell (RBC) count, hemoglobin levels, total protein (TP) levels, albumin levels, and laboratory indicators of renal function. TP levels > 68.45 g/L were independent risk factors for patients in the nephrology department (odds ratio (OR) = 1.01, 95% confidence interval (CI) = 1.001-1.024, P = 0.04), and RBC count < 3.79 × 10 12 /L was an independent risk factor for orthopedic inpatients (OR = 0.49, 95% CI 0.268-0.913, P = 0.02). Therefore, nephrologists should pay attention to the TP level of hospitalized patients to facilitate the early identification of MM in patients with chronic kidney disease. Orthopedic surgeons should pay attention to RBC counts in patients with fractures, and patients with low RBC counts should avoid unnecessary surgery and move to specialist care as early as possible., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although lipid metabolism has been proven to play a key role in the development of cancer, its significance in uveal melanoma (UM) has not yet been elucidated in the available literature., Methods: To identify the expression patterns of lipid metabolism in 80 UM patients from the TCGA database, 47 genes involved in lipid metabolism were analyzed. Consensus clustering revealed two distinct molecular groups. ESTIMATE, TIMER, and ssGSEA analyses were done to identify the differences between the two subgroups in tumor microenvironment (TME) and immune state. Using Cox regression and Lasso regression analysis, a risk model based on differentially expressed genes (DEGs) was developed. To validate the expression of monoacylglycerol lipase (MGLL) and immune infiltration in diverse malignancies, a pan-cancer cohort from the UCSC database was utilized. Next, a single-cell sequencing analysis on UM patients from the GEO data was used to characterize the lipid metabolism in TME and the role of MGLL in UM. Finally, in vitro investigations were utilized to study the involvement of MGLL in UM., Results: Two molecular subgroups of UM patients have considerably varied survival rates. The majority of DEGs between the two subgroups were associated with immune-related pathways. Low immune scores, high tumor purity, a low number of immune infiltrating cells, and a comparatively low immunological state were associated with a more favorable prognosis. An examination of GO and KEGG data demonstrated that the risk model based on genes involved with lipid metabolism can accurately predict survival in patients with UM. It has been demonstrated that MGLL, a crucial gene in this paradigm, promotes the proliferation, invasion, and migration of UM cells. In addition, we discovered that MGLL is strongly expressed in macrophages, specifically M2 macrophages, which may play a function in the M2 polarization of macrophages and M2 macrophage activation in cancer cells., Conclusion: This study demonstrates that the risk model based on lipid metabolism may be useful for predicting the prognosis of patients with UM. By promoting macrophage M2 polarization, MGLL contributes to the evolution of malignancy in UM, suggesting that it may be a therapeutic target for UM., 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. The reviewer HC declared a shared parent affiliation with the author CZ to the handling editor at the time of review., (Copyright © 2023 Tan, Pan, Deng, Chen, Xia, Liu, Zou and Qin.)

Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), and m6A recognition proteins (readers). Aberrant regulation of m6A modification is pivotal for tumorigenesis, progression, invasion, metastasis, and apoptosis of malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized by the 2018 Nobel Prize in Medicine and Physiology. However, not all cancer patients response to ICI therapy, which is thought to be the result of intricate immune escape mechanisms. Recently, numerous studies have suggested a novel role for m6A epigenetic modification in the regulation of tumor immune evasion. Herein, we review the relevant mechanisms of m6A regulators in regulating various key signaling pathways in cancer biology and how m6A epigenetic modifications regulate the expression of immune checkpoints, opening a new window to understand the roles and mechanisms of m6A epigenetic modifications in regulating tumor immune evasion. In addition, we highlight the prospects and development directions of future combined immunotherapy strategies based on m6A modification targeting, providing directions for promoting the treatment outcomes of immune checkpoint inhibitors., 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 Pan, Huang, Deng and Zou.)

Objective: In 2022, a new coronavirus variant (Omicron) infection epidemic broke out in Shanghai, China. However, it is unclear whether the duration of this omicron variant is different from that of the prototype strain., Methods: We retrospectively analyzed 157 cases of Omicron variant infection in Taizhou Public Health Center from March 29, 2022, to April 18, 2022, and observed the dynamics of nucleic acid Ct values during the admission and discharge of patients. Clinical and laboratory indicators of these patients were also obtained., Results: Compared to the prototype strain, the Omicron variant showed a broad population susceptibility in infected individuals (regardless of age and presence of underlying disease) and had slight damage to the immune system and renal function; the viral loads peaked was 2-3 days from disease onset; the median duration of omicron variant was 15-18 days; the nucleic acid Ct value of nasopharyngeal swabs of infected patients is lower than that of throat swabs, and the Ct value of oropharyngeal swabs is unstable during the recovery period., Conclusion: Therefore, we found that the time to peak viral load of this Omicron variant was 2-3 days after the onset of the disease, and the duration was 15-18 days; symptomatic patients had higher viral load and longer hospitalization time. This finding will provide a basis for understanding omicron variants and formulating the national prevention and control strategy., 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 Zhou, Hu, Zhao, Chi, Pan, Zheng, Bi, Chen, Xie, Xu, Tung, Shen and Zhu.)

Four new sesquiterpenoids named atrchiterpenes A-D (1-4), a new natural product (5), and twelve known compounds (6-17) were isolated from Atractylodes chinensis (DC.) Koidz. Compound 1 was a rare N-containing eudesmane-type sesquiterpenoid. Structure elucidation was performed by spectroscopic techniques, including 1D, 2D NMR spectra, and HR-ESI-MS. Compounds 6-11, 14, and 17 were reported from Atractylodes for the first time. All the isolated compounds were evaluated for cytotoxicity activity. Compound 16 showed moderate cytotoxicity against HepG2 cells with an IC 50 value of 5.81±0.47., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

The physical condition of individuals who contracted COVID-19 had a profound influence on mitigating the physical and psychological impact of the disease and the symptoms of posttraumatic stress disorder (PTSD). Little attention has been focused on the influence of physical condition on PTSD among recovered COVID-19 subjects. This study explored the relationship between physical and psychological status and PTSD and the potential mechanisms. Questionnaires were completed by 73 (50.7%, 73/144) COVID-19 recovered subjects who were diagnosed in Taizhou, Zhejiang, China. We conducted a face-to-face survey from January 17 to March 10, 2020. The mediation analysis approach was applied in this research. Our data show that recovered COVID-19 subjects who were in better physical condition exhibited fewer psychological problems [B (95%CI), (-1.65 -3.04, -0.26)] and lower PTSD [B (95%CI), -6.13 (-9.43, -2.83)]. In addition, the worse the psychological status of recovered COVID-19 subjects was, the stronger the PTSD (B [95%CI], 0.58 [0.02, 1.14]). Moreover, psychological status could significantly mediate the impact of physical condition on PTSD ( β 1 θ2 = -0.87). Together, COVID-19 recovered subjects who have better physical condition could decrease their PTSD, and the worse the physical condition of COVID-19 recovered subjects would increase their psychological problems. Our finding about psychological status could significantly mediate the impact of the physical condition on PTSD might be useful for medical institutions and the government seeking to help with the follow-up rehabilitation training of recovered COVID-19 subjects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Chi, Wang, Zheng, Pan, Yu, Xu, Zhu, Li, Chen, Zhao, Wu, Shen, Tung and Luo.)

Endogenous retroviruses (ERVs), deriving from exogenous retroviral infections of germ line cells occurred millions of years ago, represent ~8% of human genome. Most ERVs are highly inactivated because of the accumulation of mutations, insertions, deletions, and/or truncations. However, it is becoming increasingly apparent that ERVs influence host biology through genetic and epigenetic mechanisms under particular physiological and pathological conditions, which provide both beneficial and deleterious effects for the host. For instance, certain ERVs expression is essential for human embryonic development. Whereas abnormal activation of ERVs was found to be involved in numbers of human diseases, such as cancer and neurodegenerative diseases. Therefore, understanding the mechanisms of regulation of ERVs would provide insights into the role of ERVs in health and diseases. Here, we provide an overview of mechanisms of transcriptional regulation of ERVs and their dysregulation in human diseases.

Bupleurum chinense DC. is a traditional Chinese medicine with a long medicinal history and is often used as the main ingredient in prescription drugs for epilepsy. The aerial parts of B. chinense DC. have similar efficacy and composition to B. chinense DC. Therefore, we speculated that the aerial parts of B. chinense DC. could be used in the treatment of epilepsy. Polysaccharides from the aerial parts of B. chinense DC. were selected to explore their therapeutic effects on epilepsy and their potential mechanism of action. The study is aimed at clarifying the antiepileptic effects of the polysaccharides from the aerial parts of B. chinense DC. and their potential underlying mechanisms. The chemical profile of the aerial parts of B. chinense DC. polysaccharides (ABP) was characterized by FT-IR spectrum and HPLC chromatogram. To determine the therapeutic effects of ABPs on epilepsy, we established a kainic acid- (KA-) induced rat model of epilepsy, and through H&E staining, Nissl staining, immunohistochemistry, biochemical analysis, ELISA, and Western blot analysis, we explored the mechanisms underlying the therapeutic effects of ABPs on epilepsy. The monosaccharide content of ABP included galacturonic acid (45.19%), galactose (36.63%), arabinose rhamnose (12.13%), and mannose (6.05%). Moreover, the average molecular weight of ABP was 1.38 × 10 3  kDa. ABP could improve hippocampal injuries and neuronal function in the KA-induced epilepsy rat model. ABP significantly inhibited oxidative stress in the hippocampus of KA-induced rats. More importantly, ABP could regulate TREM2 activation in the PI3K/Akt/GSK-3 β pathway to inhibit neuronal apoptosis, including increasing the expression of superoxide dismutase and lactate dehydrogenase and decreasing the expression of malondialdehyde. The current study defined the potential role of ABP in inhibiting the development of epilepsy, indicating that ABP could upregulate TREM2 to alleviate neuronal apoptosis, by activating the PI3K/Akt/GSK-3 β pathway and oxidative stress in epilepsy., 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., (Copyright © 2022 Xiaomao Li et al.)

Nitrogen and sulfur co-doped carbon dots (N,S-CDs) have been widely studied with high quantum yield (QY). The experimental conditions of three different N,S-CDs were optimized. Emission peak position of three different N,S-CDs shown almost remains unchanged or obvious excitation-dependent PL properties, that was likely owed to size distribution. In order to discuss the N,S-CDs stability of photoluminescence property in environment, various experiments such as the photostability, different pH, ionic strengths and temperature were designed. To sum up, three different N,S-CDs exhibited discrepancy property. Molecular interaction of three different N,S-CDs were produced via vary carbon source with human serum albumins have been investigate by various methods. The quenching mechanism, thermodynamic and kinetic parameters, binding sites, electrochemical behavior of three different N,S-CDs with human serum albumins have some different, but conformational change of three different N,S-CDs with human serum albumins alike. The molecular docking had successful applied to study the N,S-CDs interaction with HSA. Different N,S-CDs possessed various characteristic that will have different quenching mechanism when they interaction with human serum albumin, study the mechanism of action at molecular level will help people to choose suitable CDs to apply in nanomedical., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to evaluate the efficacy of an extracellular matrix scaffold with multilayer decellularized tendon slices (MDTSs) for reconstructing large rotator cuff tears in a rabbit model., Methods: Large defects in the infraspinatus tendons were created bilaterally in 36 rabbits. The graft group underwent bridging repair of the defects with the MDTSs grafts from Achilles tendons of adult beagle dogs, and the control group underwent repair with the autologous excised tendon. Specimens underwent histologic observation, biomechanical testing, and microcomputed tomography analysis at 2, 4, and 8 weeks after surgery., Results: Histologic analysis confirmed that the MDTSs graft promoted cell ingrowth and tissue integration, and fibrocartilage and Sharpey fibers formed at the enthesis at 8 weeks. Accordingly, the MDTSs graft generated a histologic appearance similar to that of the autogenous tendon graft. Mechanical testing revealed a significant increase of the regenerated tendons in ultimate load and stiffness from 4 to 8 weeks postoperatively, which was similar to autologous tendon repair. Microcomputed tomography analysis demonstrated that the MDTSs graft promoted bone formation at the tendon-bone insertion, thus improving the mechanical properties of the repair tendon., Conclusions: The MDTSs graft used to bridge large rotator cuff defects in a rabbit model promoted host cell ingrowth, enhanced the remodeling of regenerated tendon, and promoted fibrocartilage formation, thus improving the biomechanical properties of the repaired tendon. This study thereby provides fundamental information for rotator cuff regeneration with the MDTSs graft., Clinical Relevance: Rotator cuff regeneration using MDTSs grafts is a promising procedure for large rotator cuff tears., (Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

Objective: To investigate the effect of canine decellularized tendon slices (DTSs) on tendon-bone healing in repairing rotator cuff injury of rabbit., Methods: Canine DTSs were prepared by repetitive freeze/thaw 5 times combined with nuclease processing for 12 hours from the adult Beagles Achilles tendons. Histological observation and cytocompatibility evaluation for the canine DTSs were performed in vitro. Twenty-four mature male New Zealand white rabbits, weighing 2.5-3.0 kg, were randomly selected. U-shaped defect of more than 50% of normal tendon in width and 8 mm in length was made in infraspinatus tendons of unilateral limb as the experimental group; the canine DTSs were used to repair defect, and the insertion of infraspinatus tendon on greater tuberosity of humerus was reconstructed in the experimental group. No treatment was done on the contralateral limb as the control group. At 4, 8, and 12 weeks after operation, the specimens were harvested for histological observation and biomechanical test., Results: Histological examination showed that collagen fibers of canine DTSs were well preserved, without residual cells. The cytocompatibility examination showed that fibroblasts attached well to canine DTSs. Biomechanical test showed that the maximum load and stiffness increased significantly with time, and the maximum load and stiffness at 12 weeks were significantly higher than those at 4 and 8 weeks (P < 0.05). The maximum load and stiffness of the experimental group at 4 and 8 weeks were significantly lower than those of the control group (P < 0.05). The stiffness of the experimental group at 12 weeks was significantly lower than that of the control group (t = -5.679, P = 0.000), but no significant difference was found in the maximum load at 12 weeks between 2 groups (t = -0.969, P = 0.361). Histological observation showed that the control group displayed a 4-layer structure of the tendon-bone insertion. In the experimental group at 4 weeks, the tendon-bone interface was filled with granulation tissue, and a small amount of Sharpey's fibers-like connected the tendon to bone; granulation tissue disappeared, and fibroblasts, Sharpey's fiber, new cartilage, and chondrocytes significantly increased with time; tendon-bone interface became mature, but the tide line was not observed between the unmineralized fibrocartilage and mineralized fibrocartilage., Conclusion: Canine DTSs prepared by repetitive freeze/thaw 5 times combined with nuclease processing for 12 hours, can enhance the healing of host tendon-bone and improve the biomechanical characteristics of the rabbit infraspinatus tendon.

Objective: To observe the therapeutic effect of Qingling Dingxuan Decoction (QDD) on vertigo caused by insufficient blood-supply of ventebrobasilar artery (IBVA)., Methods: Thirty-nine patients were divided into the flunarizine group (n=19) and the QDD group (n=20) treated with respective medicine on the base of routine treatment with Chinese and Western medicine. The clinical efficacy and recurrent rate were observed and compared., Results: Compared with those in the flunarizine group, clinical curative effect was better, recurrent rate lower, symptom score higher, hemorheological parameters and transcranial doppler indexes were improved more significant in the QDD group (P < 0.01 or P < 0.05)., Conclusion: QDD had obvious therapeutic effect on IBVA. Improvement of microcirculation and reduction of blood viscosity may be one of the therapeutical mechanisms.