IRE1α pathway: A potential bone metabolism mediator.

Osteoblasts and osteoclasts collaborate in bone metabolism, facilitating bone development, maintaining normal bone density and strength, and aiding in the repair of pathological damage. Endoplasmic reticulum stress (ERS) can disrupt the intracellular equilibrium between osteoclast and osteoblast, resulting in dysfunctional bone metabolism. The inositol-requiring enzyme-1α (IRE1α) pathway-the most conservative unfolded protein response pathway activated by ERS-is crucial in regulating cell metabolism. This involvement encompasses functions such as inflammation, autophagy, and apoptosis. Many studies have highlighted the potential roles of the IRE1α pathway in osteoblasts, chondrocytes, and osteoclasts and its implication in certain bone-related diseases. These findings suggest that it may serve as a mediator for bone metabolism. However, relevant reviews on the role of the IRE1α pathway in bone metabolism remain unavailable. Therefore, this review aims to explore recent research that elucidated the intricate roles of the IRE1α pathway in bone metabolism, specifically in osteogenesis, chondrogenesis, osteoclastogenesis, and osteo-immunology. The findings may provide novel insights into regulating bone metabolism and treating bone-related diseases.

Cevanine-type steroidal alkaloids from the bulbs of Fritillaria cirrhosa D. Don.

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 µM, with inhibition ratios ranging from 5.1% to 14.3%.

Dual amplification for PEC ultrasensitive aptasensing of biomarker HER-2 based on Z-scheme UiO-66/CdIn2S4 heterojunction and flower-like PtPdCu nanozyme.

As an important prognostic indicator in breast cancer, human epithelial growth factor receptor-2 (HER-2) is of importance for assessing prognosis of breast cancer patients, whose accurate and facile analysis are imperative in clinical diagnosis and treatment. Herein, photoactive Z-scheme UiO-66/CdIn2S4 heterojunction was constructed by a hydrothermal method, whose optical property and photoactivity were critically investigated by a range of techniques, combined by elucidating the interfacial charge transfer mechanism. Meanwhile, PtPdCu nanoflowers (NFs) were fabricated by a simple aqueous wet-chemical method, whose peroxidase (POD)-mimicking catalytic activity was scrutinized by representative tetramethylbenzidine (TMB) oxidation in H2O2 system. Taken together, the UiO-66/CdIn2S4 based photoelectrochemical (PEC) aptasensor was established for quantitative analysis of HER-2, where the detection signals were further magnified through catalytic precipitation reaction towards 4-chloro-1-naphthol (4-CN) oxidation (assisted by the PtPdCu NFs nanozyme). The PEC aptasensor presented a broader linear range within 0.1 pg mL-1-0.1 µg mL-1 and a lower limit of detection of 0.07 pg mL-1. This work developed a new PEC aptasensor for ultrasensitive determination of HER-2, holding substantial promise for clinical diagnostics.

[Chemical constituents from roots of Kadsura heteroclita].

The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.

Palladium-Catalyzed Directed Carbon-Carbon Bond Activation of Aryl Nitriles for Cyano Transfer.

Herein, we report the C-H cyanation of indoles via a palladium-catalyzed directed C-CN activation reaction using aryl nitrile as a cyano source. The employment of the phenoxy-oriented group is the key to the cleavage of the C-CN bond. This protocol features a broad substrate scope, good efficiency, and high regioselectivity. Furthermore, the practical application of this protocol was showcased in the late-stage functionalization and synthesis of indole derivatives, which were derived from drugs and natural products, through the process of cyanation.

Triterpenoids from the hook-bearing stems of Uncaria rhynchophylla.

An unprescribed nortriterpenoid with an aromatic E ring, uncanortriterpenoid A (1), together with fourteen known triterpenoids (2-15), were isolated from the hook-bearing stems of Uncaria rhynchophylla Miq. Based on extensive spectroscopic analyses, the NMR data of 2, 5, and 10 in CD3OD were assigned for the first time, and the wrongly assigned δC of C-27 and C-29 of 2 were revised. Among the known compounds, 7, 13, and 15 were isolated from this species for the first time, and 15 represents the first lanostane triterpenoid bearing an extra methylidene at C-24 for the Rubiaceae family. Additionally, compounds 6 and 14 exhibited moderate ferroptosis inhibitory activity, with an EC50 value of 14.74 ± 0.20 µM for 6 and 23.11 ± 1.31 µM for 14.

METTL16 promotes liver cancer stem cell self-renewal via controlling ribosome biogenesis and mRNA translation.

BACKGROUND: While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N6-methyladenosine (m6A) methyltransferase, in HCC development/maintenance, CSC stemness, as well as normal hepatogenesis. METHODS: Liver-specific Mettl16 conditional KO (cKO) mice were generated to assess its role in HCC pathogenesis and normal hepatogenesis. Hydrodynamic tail-vein injection (HDTVi)-induced de novo hepatocarcinogenesis and xenograft models were utilized to determine the role of METTL16 in HCC initiation and progression. A limiting dilution assay was utilized to evaluate CSC frequency. Functionally essential targets were revealed via integrative analysis of multi-omics data, including RNA-seq, RNA immunoprecipitation (RIP)-seq, and ribosome profiling. RESULTS: METTL16 is highly expressed in liver CSCs and its depletion dramatically decreased CSC frequency in vitro and in vivo. Mettl16 KO significantly attenuated HCC initiation and progression, yet only slightly influenced normal hepatogenesis. Mechanistic studies, including high-throughput sequencing, unveiled METTL16 as a key regulator of ribosomal RNA (rRNA) maturation and mRNA translation and identified eukaryotic translation initiation factor 3 subunit a (eIF3a) transcript as a bona-fide target of METTL16 in HCC. In addition, the functionally essential regions of METTL16 were revealed by CRISPR gene tiling scan, which will pave the way for the development of potential inhibitor(s). CONCLUSIONS: Our findings highlight the crucial oncogenic role of METTL16 in promoting HCC pathogenesis and enhancing liver CSC self-renewal through augmenting mRNA translation efficiency.

Microbiome: Role in Inflammatory Skin Diseases.

As the body's largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.

The effect of the mitochondria-targeted antioxidant Mito-tempo during sperm ultra-rapid freezing.

During the freeze-thaw process, human spermatozoa are susceptible to oxidative stress, which may cause cryodamage and reduce sperm quality. As a novel mitochondria-targeted antioxidant, Mito-tempo has been used for sperm cryopreservation. However, it is currently unknown what role it will play in the process of sperm ultra-rapid freezing. The purpose of this study was to investigate whether Mito-tempo can improve sperm quality during ultra-rapid freezing. In this study, samples with the addition of Mito-tempo (0, 5, 10, 20, and 40 µM) to sperm freezing medium were selected to evaluate the changes in sperm quality, antioxidant capacity and ultrastructure after ultra-rapid freezing. After ultra-rapid freezing, the quality and antioxidant function of the spermatozoa were significantly reduced and the spermatozoa ultrastructure was destroyed. The addition of 10 µM Mito-tempo significantly increased post thaw sperm motility, viability, plasma membrane integrity and mitochondrial membrane potential (P < 0.05). Moreover, the DNA fragmentation index (DFI), ROS levels and MDA content were reduced, and the antioxidant enzyme (CAT and SOD) activities were enhanced in the 10 µM Mito-tempo group (P < 0.05). Moreover, Mito-tempo protected sperm ultrastructure from damage. In conclusion, Mito-tempo improved the quality and antioxidant function of sperm after ultra-rapid freezing while reducing freezing-induced ultrastructural damage.

Carbon dot enhanced peroxidase-like activity of platinum nanozymes.

As one of the most intriguing nanozymes, the platinum (Pt) nanozyme has attracted tremendous research interest due to its various catalytic activities but its application is still limited by its poor colloidal stability and low affinity to substrates. Here, we design a highly stable Pt@carbon dot (Pt@CD) hybrid nanozyme with enhanced peroxidase (POD)-like activity (specific activity of 1877 U mg-1). The Pt@CDs catalyze the decomposition of hydrogen peroxide (H2O2) to produce singlet oxygen and hydroxyl radicals and exhibit high affinity to H2O2 and high specificity to 3,3',5,5'-tetramethyl-benzidine. We reveal that both the hydroxyl and carbonyl groups of CDs could coordinate with Pt2+ and then regulate the charge state of the Pt nanozyme, facilitating the formation of Pt@CDs and improving the POD-like activity of Pt@CDs. Colorimetric detection assays based on Pt@CDs for H2O2, dopamine, and glucose with a satisfactory detection performance are achieved. Moreover, the Pt@CDs show a H2O2-involving antibacterial effect by destroying the cell membrane. Our findings provide new opportunities for designing hybrid nanozymes with desirable stability and catalytic performance by using CDs as nucleating templates and stabilizers.

Ultrasensitive Plasmon-Enhanced Infrared Spectroelectrochemistry.

IR spectroelectrochemistry (EC-IR) is a cutting-edge operando method for exploring electrochemical reaction mechanisms. However, detection of interfacial molecules is challenged by the limited sensitivity of existing EC-IR platforms due to the lack of high-enhancement substrates. Here, we propose an innovative plasmon-enhanced infrared spectroelectrochemistry (EC-PEIRS) platform to overcome this sensitivity limitation. Plasmonic antennae with ultrahigh IR signal enhancement are electrically connected via monolayer graphene while preserving optical path integrity, serving as both the electrode and IR substrate. The [Fe(CN)6 ]3- /[Fe(CN)6 ]4- redox reaction and electrochemical CO2 reduction reaction (CO2 RR) are investigated on the EC-PEIRS platform with a remarkable signal enhancement. Notably, the enhanced IR signals enable a reconstruction of the electrochemical curve of the redox reactions and unveil the CO2 RR mechanism. This study presents a promising technique for boosting the in-depth understanding of interfacial events across diverse applications.

Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition: in vitro and in vivo study.

AIM: To provide the direct evidence for the crucial role of trimethylamine N-oxide (TMAO) in vascular permeability and endothelial cell dysfunction under diabetic condition. METHODS: The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells (HRMEC) under high glucose conditions was tested by a cell counting kit, wound healing, a transwell and a tube formation assay. The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction (RT-PCR). The expression of the cell junction was measured by Western blotting (WB) and immunofluorescence staining. In addition, two groups of rat models, diabetic and non-diabetic, were fed with normal or 0.1% TMAO for 16wk, and their plasma levels of TMAO, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested. The vascular permeability of rat retinas was measured using FITC-Dextran, and the expression of zonula occludens (ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining. RESULTS: TMAO administration significantly increased the cell proliferation, migration, and tube formation of primary HRMEC either in normal or high-glucose conditions. RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation, while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment. Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage, which were even higher in TMAO-feeding diabetic rats. Furthermore, TMAO administration increased the rat plasma levels of VEGF, IL-6 and TNF-α while decreasing the retinal expression levels of ZO-1 and claudin-5. CONCLUSION: TMAO enhances the proliferation, migration, and tube formation of HRMEC, as well as destroys their vascular integrity and tight connection. It also regulates the expression of VEGF, IL-6, and TNF-α.

A New Surgical Assistance Aid for Mesiodens Extraction Based on the Ideal Approach.

BACKGROUND: To date, the classification of mesiodens has been based on the location, crown orientation, and morphology; however, there is no assistance aid focusing on choosing surgical approach. PURPOSE: This study aimed to introduce and evaluate a new surgical assistance aid for mesiodens extraction based on surgical approach. STUDY DESIGN, SETTING, SAMPLE: For the retrospective trial part of this study, case data from mesiodens patients who had surgery at the Affiliated Stomatological Hospital was collected, and a new surgical assistance aid was developed. A prospective randomized controlled trial was conducted on mesiodens patients who were seen in our department (patients with one mesiodens were included). PREDICTOR VARIABLE: The predictor variable was surgical approach either with or without the surgical assistance aid. Subjects were randomized to one of the two study groups. For subjects assigned to the group using the surgical assistance guide, the approach was selected according to the aid detailed in this study. For subjects assigned to the group without the surgical assistant aid, 2 residents chose an approach based on their judgment and review of relevant imaging and physical examination. MAIN OUTCOME VARIABLES: The preoperative evaluation time, operative time, and complications associated with surgery were recorded separately for the two groups. COVARIATES: The age and sex were also recorded. ANALYSES: Variables were analyzed using the independent t-test and χ2 test. The level of statistical significance is P < .05. RESULTS: In the retrospective trial part, a new surgical assistance aid for mesiodens extraction was developed based on the ideal surgical approach. In the prospective randomized controlled trial, the experimental group (n = 50) was statistically significant in preoperative evaluation time (4.51 ± 0.34 mins vs 5.43 ± 0.34 mins) and operative time (31.87 ± 5.57 mins vs 36.32 ± 5.28 mins) compared to the control group (n = 50) (P < .001). There was no significant intergroup difference in complications associated with surgery (P > .05). CONCLUSION AND RELEVANCE: The new surgical assistance aid developed in this study guides surgeons to ease the selection of surgical approaches and shorten the operative time.

RNA m6A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression.

As the most common internal modification of mRNA, N6-methyladenosine (m6A) and its regulators modulate gene expression and play critical roles in various biological and pathological processes including tumorigenesis. It was reported previously that m6A methyltransferase (writer), methyltransferase-like 3 (METTL3) adds m6A in primary microRNAs (pri-miRNAs) and facilitates its processing into precursor miRNAs (pre-miRNAs). However, it is unknown whether m6A modification also plays a role in the maturation process of pre-miRNAs and (if so) whether such a function contributes to tumorigenesis. Here, we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia (AML) patients, especially in relapsed patients, and plays an oncogenic role in AML. Moreover, YTHDF2 promotes expression of miR-126-3p (also known as miR-126, as it is the main product of precursor miR-126 (pre-miR-126)), a miRNA that was reported as an oncomiRNA in AML, through facilitating the processing of pre-miR-126 into mature miR-126. Mechanistically, YTHDF2 recognizes m6A modification in pre-miR-126 and recruits AGO2, a regulator of pre-miRNA processing, to promote the maturation of pre-miR-126. YTHDF2 positively and negatively correlates with miR-126 and miR-126's downstream target genes, respectively, in AML patients, and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis, indicating that miR-126 is a functionally important target of YTHDF2 in AML. Overall, our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the therapeutic potential of targeting this axis for AML treatment, but also suggest that m6A plays a role in pre-miRNA processing that contributes to tumorigenesis.

Herb pairs containing Curcumae Rhizoma (Ezhu): A review of bio-active constituents, compatibility effects and t-copula function analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: An herbal pair is a classic form of clinical dispensing in Traditional Chinese Medicine (TCM), often used in prescriptions to enhance the effect or reduce potential side effects. It is the smallest component unit of Chinese medicine prescription and an essential bridge between Chinese medicine and prescription. Curcumae Rhizoma (called Ezhu in Chinese) is a representative TCM herb that promotes blood circulation and removes blood stasis. It has been used in Chinese medicine for thousands of years. Ezhu is generally used in clinical applications as a part of a "drug pair" to treat heartburn, stomach pain, tumour, amenorrhea and abdominal pain caused by blood stasis, qi stagnation and injury. AIMS OF THE REVIEW: This review aims to summarize the latest and comprehensive situation of the biological activity and clinical application of drug pairs containing Ezhu, find the law of Ezhu compatibility application, and discuss the rationalization of Ezhu drug compatibility. For Ezhu, herb pairs to provide a theoretical basis for clinical research in TCM and serve as a research foundation for developing new drugs. MATERIALS AND METHODS: Using a self-built prescription database and Apriori algorithm for association rule mining. A systematic search for studies on herb pairs containing Ezhu was carried out by using the internet databases of PubMed, CNKI, Baidu Scholar, Google Scholar and Web of Science, as well as other relevant textbooks, reviews and documents (e.g. Chinese Pharmacopoeia, 2020 edition, Chinese herbal classic books and PhD and MSc theses, etc.). Among them with keywords including "Curcumae Rhizoma", "Ezhu", "herb pairs", "clinical application", etc. and their combinations. Moreover, the t-copula function was used to analyse the dose-coupling effect of five drug pairs, including Ezhu. RESULTS: The preliminary statistical analysis retrieved Ezhu prescriptions from self-built prescription database and internet databases. The results showed that the compatibility frequency of Ezhu with the other five Chinese medicines was high. Most of these selected herbal combinations are used to treat internal diseases. In this paper, the progress of the ethnopharmacology of Ezhu was reviewed, emphasizing the changes in bioactive components and compatibility of Chinese traditional medicine combinations such as Ezhu and Astragalus Curcuma (Sparganium stoloniferum Buch. -Ham; called Sanleng in Chinese), Ezhu and Astragali Radix (Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Astragalus membranaceus (Fisch.) Bge.; called Huangqi in Chinese). Some other varieties, such as Ezhu and Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.; called Chuanxiong in Chinese), Trionycis Carapax (Trionyx sinensis Wiegmann; called Biejia in Chinese), and Coptidis Rhizoma (Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, Coptis teeta Wall.; called Huanglian in Chinese), are also recorded in ancient books but rarely researched. The dose of Ezhu is strongly correlated with the amount of Sanleng, Huangqi, Biejia, Chuanxiong and Huanglian, respectively. Furthermore, there was a positive correlation between them. CONCLUSIONS: The bioactive components and compatibility effects of Ezhu herb pairs were studied in detail using data mining and t-copula function analysis. Ezhu and Astragalus Curcuma (Sanleng) mainly treat gynecological disorders by activating blood circulation and relieving congestion. Ezhu and Astragali Radix (Huangqi) drug pair and Ezhu and Trionycis Carapax (Biejia) drug pair are all commonly used in the clinical treatment of tumors, the former is mainly used clinically for the treatment of digestive tract-related inflammation and tumors, liver cancer and gynecological tumors, and the latter is commonly used for the treatment of malignant tumors, such as liver cancer and mammary cancer.

RNA Modifications in Cancer Metabolism and Tumor Microenvironment.

RNA modifications have recently been recognized as essential posttranscriptional regulators of gene expression in eukaryotes. Investigations over the past decade have revealed that RNA chemical modifications have profound effects on tumor initiation, progression, refractory, and recurrence. Tumor cells are notorious for their robust plasticity in response to the stressful microenvironment and undergo metabolic adaptations to sustain rapid cell proliferation, which is termed as metabolic reprogramming. Meanwhile, cancer-associated metabolic reprogramming leads to substantial alterations of intracellular and extracellular metabolites, which further reshapes the tumor microenvironment (TME). Moreover, cancer cells compete with tumor-infiltrating immune cells for the limited nutrients to maintain their proliferation and function in the TME. In this chapter, we review recent interesting findings on the engagement of epitranscriptomic pathways, especially the ones associated with N6-methyladenosine (m6A), in the regulation of cancer metabolism and the surrounding microenvironment. We also discuss the promising therapeutic approaches targeting RNA modifications for anti-tumor therapy.

Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice.

Cyclosporine (CsA) is an immunosuppressive agent that often causes acute kidney injury (AKI) in children. The specific mechanisms underlying CsA-induced AKI are currently unknown. This study used an integrated network analysis of microRNA (miRNA) and mRNA expression profiles, biochemical and pathological analyses to further investigate these potential mechanisms of CsA-induced AKI. Small RNA sequence analysis identified 25 differentially expressed miRNAs, RNA sequencing analysis identified 4,109 differentially expressed mRNAs. We obtained a total of 4,367 target genes from the 25 differentially expressed miRNAs based on three algorithms, including the Mirdb, Mirtarbase, and TargetScan. 971 target genes overlapped between the 4,367 target genes and 4,109 differentially expressed mRNAs were identified for further bioinformatics analysis. Finally, 30 hub genes and two main modules were recognized. Functional enrichment analysis of 30 hub genes indicated that inflammation and epithelial-mesenchymal transition (EMT) related genes were mainly concentrated together. Pathway analysis revealed that the PI3K-Akt signaling pathway plays an integral role in CsA-induced AKI. Network analysis identified 3 important miRNAs, mmu-miR-17b-5p, mmu-miR-19b-3p, and mmu-mir-423-5p that may further promote the development of inflammatory responses and EMT by mediating a complex network of factors. Our research provides a clearer understanding the molecular mechanism of this specific drug-induced AKI by CsA use, which is useful for discovering potential targets for gene therapies, and drug development in CsA-induced AKI.

Changes in mental health among Chinese university students before and during campus lockdowns due to the COVID-19 pandemic: a three-wave longitudinal study.

The campus lockdown due to the COVID-19 pandemic has adversely affected mental health among university students. However, the heterogeneity in responses to campus lockdown is still poorly known. We collected three-wave prospective data on university students' mental health in Shanghai, China, in 2022: (i) in February before the pandemic; (ii) in April at the initial COVID-19 campus lockdown; and (iii) in May amidst the citywide lockdown. Overall, 205 university students completed sociodemographic questionnaires, the General Health Questionnaire-12 items (GHQ-12), and the Depression, Anxiety and Stress Scale-21 items (DASS-21). Generalized estimating equations were used to examine the longitudinal changes in mental health and symptoms of depression, anxiety, and stress. Latent class mixed models (LCMM) were constructed to identify distinct trajectories. Multinomial regression models were used to identify factors associated with status variation patterns. Mean GHQ-12 scores were 8.49, 9.66, and 11.26 at pre-pandemic and lockdown T1 and T2, respectively (p < 0.001). Mean scores for depression, anxiety, and stress were (5.96, 10.36, and 8.06, p < 0.001), (7.13, 6.67, and 7.16, p = 0.243), and (9.83, 7.28, and 11.43, p < 0.001), respectively. Changing trends of numbers of participants with clinical symptoms were consistent with those of mean scores. LCMM fitted three distinct trajectory classes, respectively, for GHQ-12, depression and anxiety symptoms, and four classes for stress symptoms. Participants with fair or poor peer relationships were more likely to belong to vulnerable trajectories concerning depression, anxiety, and stress symptoms. This study proves heterogeneity in mental health of university students in response to pandemic campus lockdown and highlights the necessity for identifying vulnerable groups to provide targeted support in future pandemics.

Bacterial Etiology and Antimicrobial Resistance Pattern of Pediatric Bloodstream Infections in Beijing, 2015-2019.

Purpose: Bloodstream infections (BSIs) was an essential cause of morbidity and mortality in children. Empiric broad-spectrum treatment of BSIs may be costly and unable to effectively eliminate the correct pathogenic microbes, resulting in downstream antimicrobial resistance. The purpose was to provide evidence for diagnosis and treatment of bloodstream infections in pediatrics, by revealing the pathogen distribution and antibiotic resistance pattern of BSIs. Methods: In this 5-year study, a total of 2544 pathogenic bacteria stains, isolated from 2368 patients with BSI, were retrospectively analyzed, to define the species distribution and the antimicrobial resistance pattern in Beijing. Results: The most frequently isolated pathogenic bacteria were K. pneumoniae (12.1%), S. aureus (11.5%), E. coli (11.2%), and E. faecium (11.2%). Hematological malignancies were the most common disease among patients with underlying conditions. Methicillin resistance was detected in 30.0% of S. aureus and 81.7% of coagulase-negative Staphylococcus (CoNS), respectively. The detection rates of carbapenem-resistant-E. coli (CRECO) and carbapenem-resistant-K. pneumoniae (CRKPN) were 10.8% and 50.8%, respectively. In terms of 122 isolates of S. pneumonia, 5 isolates (4.1%) were penicillin-resistant Streptococcus pneumoniae (PRSP); meanwhile, 50 isolates (41.0%) were penicillin-intermediate Streptococcus pneumoniae (PISP). Among the non-fermentative gram-negative bacilli isolates, 22.8% and 26.9% of the P. aeruginosa, were resistant to imipenem and meropenem. Furthermore, the resistance rates of A. baumannii to imipenem and meropenem both were 54.5%. Conclusion: In the study, we demonstrated the characteristics of bloodstream infections and antimicrobial susceptibility pattern of pediatrics in Beijing. Gram positive bacteria were the main pathogens of BSIs. CoNS strains presented even higher resistance to multiple antibiotics, including methicillin, than S. aureus. K. pneumoniae and E. coli represent the most common isolated gram-negative bacteria and exhibited high resistance to a variety of antimicrobial agents. Therefore, it was of critical importance to implement appropriate antimicrobial medication according to pathogen distribution and drug susceptibility test.

Application of digital guide plate with drill-hole sharing technique in the mandible reconstruction.

Background/purpose: With the development of computer-assisted surgery, digital guide plate was widely used in vascularized bone flap grafts for mandibular reconstruction. The purpose of this study was to design and manufacture a digital guide plate with drill-hole sharing for mandibular reconstruction and assess for surgical accuracy. Materials and methods: 17 patients that required mandibular reconstruction using fibula free flap or iliac crest free flap were included in the study. The computed tomography (CT) data of the patient's mandible and pelvis or fibula were acquired preoperatively. A surgical simulation was then performed using computer-aided surgical simulation (CASS) technology based on above date, which allowed the design of two cutting guide and a repositioning guide for mandibular reconstruction. After surgery, the accuracy of reconstruction was evaluated by superimposing the postoperative image onto the preoperative image of mandible, recording the linear and angular deviation of landmarks, measuring the differences between the planned and actual outcomes. Results: The osteotomy and repositioning of fibula or iliac crest segments were successfully performed as planned using surgical guides. The digital guide plate with drill-hole sharing showed excellent accuracy, When the iliac crest or the fibula free flap were used for mandibular reconstruction, the largest mean differences between the preoperative and postoperative were 1.11 mm and 2.8° or 1.3 mm and 3.87°. Conclusion: The digital guide plate with drill-hole sharing designed preoperatively provides a reliable method of for the mandibular reconstruction. This can assist surgeons in accurately performing osteotomy and repositioning fibula or iliac crest segments during the mandibular reconstruction.