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Abstract Objective To investigate the clinical efficacy of transumbilical single-incision laparoscopic surgery in the treatment of complicated appendicitis in overweight/obese adolescents. Methods A retrospective analysis was conducted on the clinical data of 226 adolescent patients with complicated appendicitis who were admitted to our hospital from January 2014 to June 2022. Among them, 102 cases underwent transumbilical single-incision laparoscopic appendectomy as the observation group, and another 124 cases underwent conventional three-port laparoscopic appendectomy as the control group. The surgical time, intraoperative blood loss, duration of incisional pain, postoperative flatus time, length of hospital stay, surgical site infection (SSI), satisfaction with cosmetic result, and occurrence of postoperative complications were compared between the two groups. Results Both groups completed the surgery smoothly, and there were no statistically significant differences in gender, age, BMI, duration of illness, white blood cell count, and preoperative CRP value between the two groups (P > 0.05). There were no statistically significant differences in surgical time and intraoperative blood loss between the two groups (P > 0.05). However, the observation group had shorter hospital stays, shorter duration of incisional pain, shorter postoperative time to flatus, and lower overall postoperative complication rates compared to the control group, with statistically significant differences (P

Abstract Kitaev chains in quantum dot-superconductor arrays are a promising platform for the realization of topological superconductivity. As recently demonstrated, even a two-site chain can host Majorana zero modes known as “poor man’s Majorana”. Harnessing the potential of these states for quantum information processing, however, requires increasing their robustness to external perturbations. Here, we form a two-site Kitaev chain using Yu-Shiba-Rusinov states in proximitized quantum dots. By deterministically tuning the hybridization between the quantum dots and the superconductor, we observe poor man’s Majorana states with a gap larger than 70 μeV. The sensitivity to charge fluctuations is also greatly reduced compared to Kitaev chains made with non-proximitized dots. The systematic control and improved energy scales of poor man’s Majorana states realized with Yu-Shiba-Rusinov states will benefit the realization of longer Kitaev chains, parity qubits, and the demonstration of non-Abelian physics.

Abstract Lymph node metastasis (LNM) is a common invasive feature of hepatocellular carcinoma (HCC) associated with poor clinical outcomes. Through microarray profiling and bioinformatic analyses, we identified the circ-0044539-miR-29a-3p-VEGFA axis as a potential key factor in the progression of HCC LNM. In HCC cells and nude mice, circ-0044539 downregulation or miR-29a-3p upregulation was associated with small tumor size, PI3K-AKT-mTOR pathway inactivation, and downregulation of the key LNM factors (HIF-1α and CXCR4). Furthermore, circ-0044539 was also responsible for exosomal miR-29a-3p secretion. Exosomal miR-29a-3p was then observed to migrate to the LNs and downregulate High-mobility group box transcription factor 1 (Hbp1) in Polymorphonuclear Myeloid-derived suppressor cells (PMN-MDSCs), inducing the formation of a microenvironment suitable for tumor colonization. Overall, circ-0044539 promotes HCC cell LNM abilities and induces an immune-suppressive environment in LNs through exosomes, highlighting its potential as a target for HCC LNM and HCC immunotherapy.

Abstract Background Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. Methods We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. Results Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. Conclusion Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

Abstract Purpose To compare the effects of a single-port-plus-one robotic laparoscopic-modified Lich–Gregoir direct nipple approach and traditional laparoscopic Cohen in treating pediatric primary obstructive megaureter. Materials and methods The clinical data of 24 children with primary obstructive megaureter from January 2021 to November 2021 were analyzed retrospectively. Among them, 12 children (8 boys and 4 girls, the average age were 17.17 ± 6.31 months) treated with the laparoscopic Cohen method were defined as group C. The remaining 12 children (7 boys and 5 girls, the average age was 17.33 ± 6.99 months) underwent single-port-plus-one robotic laparoscopic-modified Lich–Gregoir direct nipple ureteral extravesical reimplantation were defined as group L. The parameters of pre-operation, intraoperative and postoperative were compared. Results There were no differences in the patient characteristics and average follow-up time between the two groups (P > 0.05).The obstruction resolution rate was 100% in both groups. The total operation time in group L is slightly longer than that in group C(P 0.05). The postoperative parameters included blood loss, gross haematuria time, indwelling catheterization time and hospitalization time in group L is shorter than group C(P 0.05). Conclusion Single-port-plus-one robot-assisted laparoscopic-modified Lich–Gregoir direct nipple approach and traditional laparoscopic Cohen are both dependable techniques for ureteral reimplantation in the treatment of pediatric primary obstructive megaureter. Since Lich–Gregoir can preserve the physiological direction of the ureter and direct nipple reimplantation enhances the effect of anti-refluxing, this technique is favorable for being promoted and applied in robot surgery.

Abstract Objective To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. Methods The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients’ characteristics as well as their perioperative and follow-up data were collected and evaluated. Results There was no significant difference in the data regarding patients’ characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P

ObjectiveThe purpose of this study is to compare the intraoperative and postoperative outcomes of a trans-umbilical single-site plus one robot-assisted surgery and a trans-umbilical single-site laparoscopic surgery in the treatment of choledochal cysts.MethodsWe retrospectively analyzed clinical data from 49 children diagnosed with choledochal cysts who were admitted to our hospital between June 2020 and December 2023. Among these patients, 24 underwent a trans-umbilical single-site plus one Da Vinci robot-assisted surgery (the robot group) and 25 underwent a trans-umbilical single-site laparoscopic-assisted surgery (the laparoscopic group). We compared differences in intraoperative and postoperative outcomes between the two groups.ResultsThere was no significant difference between the two groups of patients in terms of gender, age, weight, clinical symptoms, maximum cyst diameter, type, postoperative complications, and facial expression, leg movement, activity, crying, and comfortability (FLACC) scoring (p > 0.05). Compared with the patients in the laparoscopic group, those in the robot group had less intraoperative bleeding [10 (8–12) vs. 15 (11.5–18) ml, p

Background: Heart failure with preserved ejection fraction (HFpEF) presents a serious risk to human health. The increased prevalence of sarcopenia in the HFpEF population has a negative impact on patient prognosis. Uric acid (UA) is the byproduct of purine metabolism and is harmful to the cardiovascular system. This study aims to establish the potential relationship between sarcopenia and serum UA in HFpEF patients. Methods: Data were obtained from 180 individuals (aged ≥60 years) with HFpEF admitted to the Geriatric Department of Jiangsu Province Hospital between January 2021 and December 2022. The UA values were grouped into 4 quartiles (Q1-Q4). Logistic generalized linear models and restricted cubic spline (RCS) regression were used to analyze the relationship between sarcopenia and UA. Subgroups based on gender were utilised for further analysis. Results: After adjusting for covariates, odds ratios (ORs) and 95 % confidence intervals (CIs) for sarcopenia prevalence in the 2nd, 3rd, and 4th quartiles were 2.56 (0.57–12.65), 4.94 (1.10–24.49), and 6.95 (1.30–44.25), respectively, unlike the 1st quartile (P for trend = 0.022). The RCS plot demonstrated a positive linear relationship between serum UA levels and sarcopenia (P for non-linearity = 0.190). A sex-based subgroup analysis revealed a statistically significant relationship between UA and sarcopenia in males (P

Abstract Three‐dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D‐RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D‐RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D‐RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor‐dependent and vendor‐independent software platforms were used to analyze the 3D‐RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D‐RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D‐RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D‐RV values should be stratified by sex, age, race, and vendor.

BackgroundImproving health care in cities with a diverse, international population is crucial for ensuring health equity, particularly for foreigners facing challenges due to cultural and language barriers. This situation is especially relevant in China, a major destination for expatriates and travelers, where optimizing health care services and incorporating international standards in the public sector are vital. Achieving this involves understanding the operational details, cultural and linguistic nuances, and advancing medical digitalization. A strategic approach focusing on cultural competence and awareness of health care systems is essential for effectively navigating health care for foreigners and expatriates in China. ObjectiveThe aim of this study was to perform an in-depth analysis of the subjective and objective experiences of local and international patients in public hospitals in China to provide a basis for enhancing the medical experience of all patients. MethodsA structured questionnaire was provided to patients at an international outpatient service of a top-tier university hospital in China. Qualitative analysis of the survey responses was performed to methodically categorize and analyze medical treatment, focusing on patient demand and satisfaction across four main category elements (“high demand, high satisfaction”; “high demand, low satisfaction”; “low demand, high satisfaction”; and “low demand, low satisfaction”), enabling a detailed cross-sectional analysis to identify areas for improvement. ResultsElements falling under “high demand, high satisfaction” for both Chinese and international patients were primarily in the realms of medical quality and treatment processes. In contrast, elements identified as “high demand, low satisfaction” were significantly different between the two patient groups. ConclusionsThe findings highlight the importance of systematic, objective research in advancing the quality of international health care services within China’s leading academic medical centers. Key to this improvement is rigorous quality control involving both patients and providers. This study highlights the necessity of certifying such centers and emphasizes the role of digital platforms in disseminating information about medical services. This strategy is expected to cater to diverse patient needs, enhancing the overall patient experience. Furthermore, by developing comprehensive diagnosis and treatment services and highlighting the superior quality and costs associated with international health care, these efforts aim to foster a sense of belonging among international patients and increase the attractiveness of China’s medical services for this demographic.

Summary: Epilepsy is a brain disorder affecting up to 1 in 26 individuals. Despite its clinical importance, the molecular mechanisms of epileptogenesis are still far from clarified. Our previous study showed that disruption of Clock in excitatory neurons alters cortical circuits and leads to generation of focal epilepsy. In this study, a GAD-Cre;Clockflox/flox mouse line with conditional Clock gene knockout in inhibitory neurons was established. We observed that seizure latency was prolonged, the severity and mortality of pilocarpine-induced seizure were significantly reduced, and memory was improved in GAD-Cre;Clockflox/flox mice. We hypothesize that mice with CLOCK knockout in inhibitory neurons have increased threshold for seizure, opposite from mice with CLOCK knockout in excitatory neurons. Further investigation showed Clock knockout in inhibitory neurons upregulated the basal protein level of ARC, a synaptic plasticity-associated immediate-early gene product, likely through the BDNF-ERK pathway. Altered basal levels of ARC may play an important role in epileptogenesis after Clock deletion in inhibitory neurons. Although sEPSCs and intrinsic properties of layer 5 pyramidal neurons in the somatosensory cortex exhibit no changes, the spine density increased in apical dendrite of pyramidal neurons in CLOCK knockout group. Our results suggest an underlying mechanism by which the circadian protein CLOCK in inhibitory neurons participates in neuronal activity and regulates the predisposition to epilepsy.

ObjectiveTo compare the efficacy of robot-assisted single-port-plus-one pyeloplasty (RSPY) and laparoscopic single-port pyeloplasty (LSPY) in the treatment of children with ureteropelvic junction obstruction (UPJO).MethodsThe clinical data of 47 children who underwent surgery for UPJO at the Department of the Pediatric Surgery of the Fujian Provincial Hospital from October 2020 to September 2022 were analyzed retrospectively. Of these 47 children, 27 received RSPY while 20 underwent LSPY. The baseline data, operation time, intraoperative anastomosis time, intraoperative blood loss, postoperative hospital stay, complications, total cost, preoperative and postoperative renal parenchymal thickness (PT), anteroposterior renal pelvis diameter (APD), and differential renal function (DRF) of the two groups were compared to evaluate the clinical efficacy of the two surgical methods.ResultsThe results showed that both surgical techniques were successful and no patient transitioned to open surgery. There was no significant difference between the two groups in baseline data, intraoperative blood loss, complications, APD, and PT 6 months after surgery. There was also no significant difference in APD, PT, and DRF 12 months after surgery (all P > 0.05). Compared with the LSPY group, the RSPY group had shorter operation time [(153.04 ± 14.44) vs. (189.90 ± 32.59) min, t = −5.24, P

Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.

Abstract Semiconductor nanowires coupled to superconductors can host Andreev bound states with distinct spin and parity, including a spin-zero state with an even number of electrons and a spin-1/2 state with odd-parity. Considering the difference in spin of the even and odd states, spin-filtered measurements can reveal the underlying ground state. To directly measure the spin of single-electron excitations, we probe an Andreev bound state using a spin-polarized quantum dot that acts as a bipolar spin filter, in combination with a non-polarized tunnel junction in a three-terminal circuit. We observe a spin-polarized excitation spectrum of the Andreev bound state, which can be fully spin-polarized, despite strong spin-orbit interaction in the InSb nanowires. Decoupling the hybrid from the normal lead causes a current blockade, by trapping the Andreev bound state in an excited state. Spin-polarized spectroscopy of hybrid nanowire devices, as demonstrated here, is proposed as an experimental tool to support the observation of topological superconductivity.

Currently, the decision boundary of the multi-class anomaly detection algorithm based on deep learning does not sufficiently capture the positive class region, posing a risk of abnormal sample features falling into the domain of normal sample features and potentially leading to misleading outcomes in practical applications. In response to the above problems, this paper proposes a new method called multi-class hypersphere anomaly detection (MMHAD) based on the edge outlier exposure set and margin. The method aims to utilize convolutional neural networks for joint training of all normal object classes, identifying a shared set of outlier exposures, learning compact identification features, and setting appropriate edge parameters to guide the model in mapping outliers outside the hypersphere. This approach enables more comprehensive detection of various types of exceptions. The experiments demonstrate that the algorithm is superior to the most advanced baseline method, with an improvement of 26.0%, 8.2%, and 20.1% on CIFAR-10 and 14.8%, 12.0%, and 20.1% on FMNIST in the cases of (2/8), (5/5), and (9,1), respectively. Furthermore, we investigate the challenging (2/18) case on CIFAR-100, where our method achieves approximately 17.4% AUROC gain. Lastly, for a recycling waste dataset with the (4/1) case, our MMHAD yields a notable 22% enhancement in performance. Experimental results show the effectiveness of the proposed model in multi-classification anomaly detection.

Abstract Background The metastasis of breast cancer (BC) is a complex multi-step pathological process, strictly dependent on the intrinsic characteristics of BC cells and promoted by a predisposing microenvironment. Although immunotherapy has made important progress in metastasis BC, the heterogeneity of PD-L1 in tumor associated macrophages (TAMs) in BC and the underlying mechanisms in the metastasis development of BC are still not completely elucidated. Small extracellular vesicles (sEVs) represent essential interaction mediators between BC cells and TAMs. It is worth noting to explore the underlying mechanisms typical of sEVs and their role in the metastasis development of BC. Methods The structure of sEVs was identified by TEM, while the particle size and amounts of sEVs were detected by BCA and NTA analysis. The specific PD-L1 + CD163 + TAM subpopulation in metastasis BC was identified by scRNA-seq data of GEO datasets and verified by IHC and IF. The function of TAMs and sEVs in metastasis BC was explored by RT-qPCR, WB, IF, flow cytometry and in vivo experiment. The expression profiles of plasma sEVs-miRNA in relation to BC metastasis was analyzed using next-generation sequencing. Further detailed mechanisms of sEVs in the metastasis development of BC were explored by bioinformatics analysis, RT-qPCR, WB and luciferase reporter assay. Results In this study, we identified that the immunosuppressive molecule PD-L1 was more abundant in TAMs than in BC cells, and a specific PD-L1 + CD163 + TAM subpopulation was found to be associated with metastasis BC. Additionally, we found that BC cells-derived sEVs can upregulate the PD-L1 expression and induce the M2 polarization, enhancing the metastasis development both in vitro and in vivo. Also, Clinical data showed that sEV-miR-106b-5p and sEV-miR-18a-5p was in relation to BC metastasis development and poor prognosis of BC patients. Further mechanistic experiments revealed that BC-derived sEV-miR-106b-5p and sEV-miR-18a-5p could synergistically promoted the PD-L1 expression in M2 TAMs by modulating the PTEN/AKT and PIAS3/STAT3 pathways, resulting in the enhancement of the BC cells invasion and metastasis. Conclusions Our study demonstrated that BC-derived sEVs can induce metastasis in BC through miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs. Therefore, the inhibition of these specific interactions of signaling pathways would represent a promising target for future therapeutic strategies for treatment of BC.

Abstract Purpose Most Hepatocellular carcinoma (HCC) patients are in advanced or metastatic stage at the time of diagnosis. Prognosis for advanced HCC patients is dismal. This study was based on our previous microarray results, and aimed to explore the promising diagnostic and prognostic markers for advanced HCC by focusing on the important function of KLF2. Methods The Cancer Genome Atlas (TCGA), Cancer Genome Consortium database (ICGC), and the Gene Expression Comprehensive Database (GEO) provided the raw data of this study research. The cBioPortal platform, CeDR Atlas platform, and the Human Protein Atlas (HPA) website were applied to analyze the mutational landscape and single-cell sequencing data of KLF2. Basing on the results of single-cell sequencing analyses, we further explored the molecular mechanism of KLF2 regulation in the fibrosis and immune infiltration of HCC. Results Decreased KLF2 expression was discovered to be mainly regulated by hypermethylation, and indicated a poor prognosis of HCC. Single-cell level expression analyses revealed KLF2 was highly expressed in immune cells and fibroblasts. The function enrichment analysis of KLF2 targets indicated the crucial association between KLF2 and tumor matrix. 33-genes related with cancer associated fibroblasts (CAFs) were collected to identify the significant association of KLF2 with fibrosis. And SPP1 was validated as a promising prognostic and diagnostic marker for advanced HCC patients. CXCR6 CD8+ T cells were noted as a predominant proportion in the immune microenvironment, and T cell receptor CD3D was discovered to be a potential therapeutic biomarker for HCC immunotherapy. Conclusion This study identified that KLF2 is an important factor promoting HCC progression by affecting the fibrosis and immune infiltration, highlighting its great potential as a novel prognostic biomarker for advanced HCC.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

Summary: Fibroblast growth factor 9 (FGF9) is a member of the fibroblast growth factor family, which is widely expressed in the central nervous system (CNS). It has been reported that deletion of FGF9 leads to defects in cerebellum development, including Purkinje cell defect. However, it is not clear how FGF9 regulating cerebellar development remains to be determined. Our results showed that in addition to disrupt Bergmann fiber scaffold formation and granule neuron migration, deletion of neuronal FGF9 led to ataxia defects. It affected development and function of Purkinje cells, and also changed the action potential threshold and excitation frequency. Mechanistically, depletion of FGF9 significantly changed neurotransmitter contents in Purkinje cells and led to preferential increase in inflammation, even downregulation in ERK signaling. Together, the data demonstrate that neuronal FGF9 is required for the development and function of Purkinje cells in the cerebellum. Insufficient FGF9 during cerebellum development will cause ataxia defects.

The blue-crowned laughingthrush Pterorhinus courtoisi (Ménégaux, 1923) is listed as a critically endangered species on the International Union for Conservation of Nature Red List. This species occupies an extremely small known breeding range in China. In this study, we obtain the complete mitochondrial genome of the blue-crowned laughingthrush by using Illumina NovaSeq sequencing. The total length of the genome is 17,875 bp, containing 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 control regions, with a slight A-T preference (52.84%) in base composition.

ABSTRACTIntroduction Objective structured clinical examination (OSCE) results could be affected by low homogeneity of examiners, non-retrospectiveness of test results, and examiner-cohort effect. In China, many students participate in medical qualification examinations, and this issue is particularly significant. This study aimed to develop a video recording, video-based rating method and compare the reliability of video and on-site ratings to enhance the quality assurance of OSCEs.Methods The subjects of this study were clinical students one year after graduation participating in the clinical skills portion of the National Medical Licensing Examination. The participants were from four cities in Jiangsu province. Participants were randomly allocated to on-site and video rating groups to evaluate the rating methods consistency. We verified the reliability of recording equipment and evaluability of video recording. Moreover, we compared the consistency and equivalence of the two rating methods and analyzed the impact of video recording on scores.Results The reliability of recording equipment and evaluability of video recording were high. Evaluation consistency between experts and examiners was acceptable, and there was no difference in evaluation results (P = 0.61). There was good consistency between video and on-site rating; however, a difference between the two rating methods was detected. The scores of video-based rating group students were lower than those of all students (P

Abstract Purpose To investigate the mechanism underlying the modulation of M1 macrophage polarization by exosomes released from hyperthermia-treated triple-negative breast cancer (TNBC) cells. Materials and methods In this study, the effects of hyperthermia on TNBC cells were examined using cell counting kit-8, apoptosis, and cell cycle assays. Transmission electron microscopy was used to identify the structure of exosomes, while bicinchoninic acid and nanoparticle tracking analysis were used to detect particle size and amounts of exosomes released after hyperthermia. The polarization of macrophages incubated with exosomes derived by hyperthermia-pretreated TNBC cells were assessed by RT-qPCR and flow cytometry analysis. Next, RNA sequencing was performed to determine the targeting molecules changed in hyperthermia-treated TNBC cells in vitro. Finally, the mechanism underlying the modulation of macrophage polarization by exosomes derived from hyperthermia-treated TNBC cells was examined by using RT-qPCR, immunofluorescence and flow cytometry analysis. Results Hyperthermia markedly reduced cell viability in TNBC cells and promoted the secretion of TNBC cell-derived exosomes. The hub genes of hyperthermia-treated TNBC cells were significantly correlated with macrophage infiltration. Additionally, hyperthermia-treated TNBC cell-derived exosomes promoted M1 macrophage polarization. Furthermore, the expression levels of heat shock proteins, including HSPA1A, HSPA1B, HSPA6, and HSPB8, were significantly upregulated upon hyperthermia treatment, with HSPB8 exhibiting the highest upregulation. Moreover, hyperthermia can induce M1 macrophage polarization by promoting exosome-mediated HSPB8 transfer. Conclusion This study demonstrated a novel mechanism that hyperthermia can induce M1 polarization of macrophages via exosome-mediated HSPB8 transfer. These results will help with future development of an optimized hyperthermia treatment regime for clinical application, especially for combination treatment with immunotherapy.

Agar, as a seaweed polysaccharide mainly extracted from Gracilariopsis lemaneiformis, has been commercially applied in multiple fields. To investigate factors indicating the agar accumulation in G. lemaneiformis, the agar content, soluble polysaccharides content, and expression level of 11 genes involved in the agar biosynthesis were analysed under 4 treatments, namely salinity, temperature, and nitrogen and phosphorus concentrations. The salinity exerted the greatest impact on the agar content. Both high (40‰) and low (10‰, 20‰) salinity promoted agar accumulation in G. lemaneiformis by 4.06%, 2.59%, and 3.00%, respectively. The content of agar as a colloidal polysaccharide was more stable than the soluble polysaccharide content under the treatments. No significant correlation was noted between the two polysaccharides, and between the change in the agar content and the relative growth rate of the algae. The expression of all 11 genes was affected by the 4 treatments. Furthermore, in the cultivar 981 with high agar content (21.30 ± 0.95%) compared to that (16.23 ± 1.59%) of the wild diploid, the transcriptional level of 9 genes related to agar biosynthesis was upregulated. Comprehensive analysis of the correlation between agar accumulation and transcriptional level of genes related to agar biosynthesis in different cultivation conditions and different species of G. lemaneiformis, the change in the relative expression level of glucose-6-phosphate isomerase II (gpiII), mannose-6-phosphate isomerase (mpi), mannose-1-phosphate guanylyltransferase (mpg), and galactosyltransferase II (gatII) genes was highly correlated with the relative agar accumulation. This study lays a basis for selecting high-yield agar strains, as well as for targeted breeding, by using gene editing tools in the future.

The hydrogenation of carbon dioxide (CO2) to produce light olefins is one of the most promising ways to utilize CO2 in power plant flue gas. However, the low concentration of CO2 (~10%) and the existence of water steam in the flue gas pose great challenges for the catalyst design. To address these problems, we introduced a Mg promoter and hydrophobic component into the Fe-based catalyst to improve the CO2 adsorption capacity and weaken the negative effects of water. The yield of light olefins on an optimized multifunctional Fe-based catalyst increased by 37% in low-concentration CO2 hydrogenation with water steam. A variety of characterizations proved that the Mg promoter played critical roles in regulating the adsorption capacity of CO2, increasing the surface electron density of Fe species, and promoting the formation of iron carbide active sites. The hydrophobic component mainly contributed to constraining the oxidation of iron carbides via water steam. It benefited from the rational design of the catalyst, showing how our multifunctional Fe-based catalyst has great potential for practical application in CO2 utilization.

PurposeTo introduce a new technique of single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple ureteral extravesical reimplantation and ascertain its validity in the treatment of pediatric primary obstructive megaureter.MethodsBetween January 2021 and November 2021, we retrospectively analyzed the clinical data of 12 children with primary obstructive megaureter who were admitted to the Department of Pediatric Surgery of Fujian Provincial Hospital. All 12 children were treated with single-port-plus-one robotic laparoscopic Lich-Gregoir direct nipple ureteral extravesical reimplantation. Five of them were female and seven were male, including nine cases were simple obstructive type, while the remaining three cases were obstructive with reflux type. The mean age of the children was 17.33 ± 6.99 (10–36) months and the mean follow-up time was 14.16 ± 1.75 (12–17) months. Changes in preoperative and first-year postoperative parameters were compared.ResultsThe mean operative time for all 12 children was 123.58 ± 10.85 (110–145) min, with a mean internal operative time of 101.42 ± 0.85 (90–120) min, a mean operative bleeding time of 2.42 ± 0.67 (2–4) ml, and a mean hematuria duration of 16.08 ± 1.44 (14–19) h. The mean indwelling catheterization time was 2.25 ± 0.45 (2–3) days and the mean hospitalization time was 3.83 ± 0.39 (3–4) days. At the postoperative first year, the ureteral diameter, calyceal diameter, and anterior–posterior renal pelvic diameter were found to be significantly smaller than at the preoperative period (18.83 ± 3.21 mm vs. 6.83 ± 1.27 mm, 13.99 ± 3.58 mm vs. 3.5 ± 2.90 mm, and 34.92 ± 4.25 mm vs. 10.08 ± 1.88 mm, P

Rolling bearing is one of the core components in rotating machinery, and its running status directly affects the operation of the whole equipment. Faults of rolling bearings in the actual working process are often multiple faults. To effectively separate fault sources, the blind source separation method is used for the compound fault diagnosis of rolling bearings. Because of the impact of the number of artificially limited decompositions and quadratic penalty factor on VMD in the decomposition process, and the slow convergence and low accuracy in the objective function of traditional FastICA operation, the VMD algorithm based on the energy loss coefficient and the information entropy is proposed, which adaptively determines the number of modal components and the quadratic penalty factor; The Tukey M estimation is selected as the objective convergence function of the FastICA algorithm to improve its robustness. First, VMD is used to decompose the signal; Secondly, the original signal and the decomposed IMF component are reconstructed, the covariance matrix and the singular value decomposition are constructed, the number of fault sources is estimated by the proximity dominance method, and the decomposed IMF components are filtered through correlation analysis and kurtosis index to build a multi-channel feature set; Finally, the constructed multi-channel feature set is input to the FastICA algorithm based on the Tukey M estimation for the separation of fault source signals to achieve composite fault diagnosis. The compound fault experiment shows that the proposed method in this paper can effectively realize the blind source separation of rolling bearing fault features to realize the compound fault diagnosis in different positions.

Background: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated. Methods: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. IHC staining was used to assess the expression of APM-related genes in clinical samples. Results: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were mined in the APMrs-high group. APM-related genes were further validated in our in-house samples. Conclusion: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients.

ObjectiveTo investigate the clinical effect of the da Vinci robotic-assisted laparoscopic pyeloureteroplasty (RALP) in treating pediatric ureteropelvic junction obstruction (UPJO).MethodsWe retrospectively analyzed clinical data from 32 children with UPJO who suffered from RALP in our hospital from October 2020 to February 2023, compared with those treated with common laparoscopy at the same time. After the establishment of the robotic arm, a mesenteric approach was performed after entering the abdominal cavity to focus on the lesion site. The dilated renal pelvis was then cut and the stenotic ureter was removed; the anastomosis and the incision were sutured by layer.ResultsA total of 62 children (44 boys and 20 girls) with a median age of 14 months (ranging from 3 to 38 months) were included. All 62 cases had hydronephrosis caused by unilateral UPJO, and the surgery was successfully completed without conversion to open. All intraoperative blood losses amounted to less than 10 ml. In the RALP group, the average operative duration was 131.28 min (ranging from 108 to 180 min). The average catheter time was 3.66 days (ranging from 2 to 7 days). The average hematuria time was 3.84 days (ranging from 2 to 6 days). The average postoperative hospital stay was 7.8 days (ranging from 6 to 12 days). The average hospitalization costs were 59,048.31 yuan (ranging from 50,484 to 69,977 yuan). The double-J tube was removed 1 month after surgery. Only one patient suffered from complications, developing a urinary tract infection 4 weeks after surgery, and was cured with the administration of oral cefaclor anti-inflammatory drugs for 3 days. All patients were followed up for 2–28 months, with a median follow-up time of 12 months. The thickness of the renal cortex was increased after surgery [(1.95 ± 0.24) vs. (4.82 ± 0.50)] cm, and the isotope renograms revealed a definite recovery of the split renal function [(28.32 ± 1.95) vs. (37.01 ± 2.71)]%.ConclusionThe robotic-assisted laparoscopic pyeloureteroplasty (RALP) in the treatment of children with upper ureteral obstruction has overall clinical efficiency. With technological advancements and an increased number of experienced surgeons, robotic surgery may become a new trend in surgery.

Abstract Background Glucose metabolism disorder is a common feature in cancer. Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non‐coding RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism‐related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer. Methods 1222 RNA‐seq were extracted from the TCGA database, and 74 glucose metabolism‐related genes were loaded from the GSEA website. Then, 7 glucose metabolism‐related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that high‐risk patients predict a poor clinical outcome with high reliability (P=2.838×10‐6). Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle‐related pathways were significantly enriched in a high‐risk group. Results Our results showed that glucose metabolism‐related lncRNAs can affect breast cancer progression. 7 glucose metabolism‐related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high‐risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis. Conclusion 7 glucose metabolism‐related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple‐negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets

Abstract Background Antiretroviral therapy (ART) is currently the most effective way to treat people living with human immunodeficiency virus (PLHs) and reduce HIV transmission. While there are many factors that reduce adherence to ART, PLHs’ knowledge about ART may determine the level of adherence. It is necessary to design and assess an instrument scale that measures the knowledge of antiretroviral therapy among PLHs. Method A cross-sectional study was conducted among PLHs in Honghe Hani and Yi Autonomous Prefecture, China. Both exploratory and confirmatory factor analyses were used to examine the latent factors of antiretroviral therapy knowledge scale. Internal consistency was assessed separately for the scale and its dimensions by estimating Cronbach’s alphas, split-half reliability and Spearman’s correlation coefficient. ANOVAs were used to compare the scores of different dimensions with sociodemographic characteristics. Results Four factors were extracted according to factor loadings. They had high internal consistency reliability (Cronbach’s alpha: 0.70–0.95) and good construct validity (standardized factor loading range: 0.46–0.86) in the scale. Goodness of fit indices indicated that a four-factor solution fit the data at an accepted level (χ2/degree ratio = 1.980, RMSEA = 0.069, GFI = 0.909, CFI = 0.957, NFI = 0.917, TLI = 0.944). ANOVAs indicated that the score was higher among PLHs who were Han, had spouses/partners, were non-famers or migrant workers, initiated ART, and had a high school or above education. Conclusion The psychometric assessment indicated that this ART knowledge scale had accepted internal consistency and discriminant construct validity. It can be used to assess the knowledge of antiretroviral therapy for PLHs.

Future search algorithm imitates the person living life. If one person finds that his life is not good, he will try to change his living life, and he will imitate a more successful person. To overcome insufficient performances of the basic Future search algorithm, this paper proposed an improved Future search algorithm based on the sine cosine algorithm (FSASCA). The proposed algorithm uses sine cosine algorithm to loop-progressive find the best solution. The searching method of the sine cosine algorithm can make the feasible solution to be re-positioned around another feasible solutions, which can make the proposed algorithm have a strong exploitation ability. Four coefficient factors are added in the basic FSA, and new update methods are introduced in the searching phase. To verify the searching and optimization performances of the proposed algorithm in this paper, this paper also gives data calculation results, Wilcoxon rank sum test, iteration figures, box plot figures, and searching path figures. Experimental results showed that FSASCA has a better iteration speed, the convergence precision, the solving accuracy, the strong competitive, and the high balance.

Abstract Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is a molecular and functional imaging modality with better restaging accuracy over conventional imaging for detecting prostate cancer in men suspected of lymph node (LN) progression after definitive therapy. However, the availability of PSMA PET/CT is limited in both low-resource settings and for repeating imaging surveillance. In contrast, CT is widely available, cost-effective, and routinely performed as part of patient follow-up or radiotherapy workflow. Compared with the molecular activities, the morphological and texture changes of subclinical LNs in CT are subtle, making manual detection of positive LNs infeasible. Instead, we harness the power of artificial intelligence for automated LN detection on CT. We examined 68Ga-PSMA-11 PET/CT images from 88 patients (including 739 PSMA PET/CT-positive pelvic LNs) who experienced a biochemical recurrence after radical prostatectomy and presented for salvage radiotherapy with prostate-specific antigen

The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose- and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.

Purpose To investigate the mechanism through which hyperthermia promotes exosome secretion and drug sensitivity in adriamycin-resistant breast cancer. Materials and Methods We first evaluated the effect of hyperthermia on adriamycin-resistant breast cancer viability and used transmission electron microscopy, nanoparticle tracking analysis, and a bicinchoninic acid kit to validate the effect of hyperthermia on exosome secretion. The effective targeting molecules and pathways changed by hyperthermia were explored by RNA microarray and verified in vitro. The adriamycin-resistant MCF-7/ADR cells co-incubated with the exosomes produced by MCF-7/ADR cells after hyperthermia were assessed. The uptake of exosomes by MCF-7/ADR cells after hyperthermia treatment was evaluated by confocal microscopy. Finally, the mechanism through which hyperthermia promotes exosome secretion by hyperthermia was determined. Results Hyperthermia significantly suppressed the growth of adriamycin-resistant breast cancer cells and increased drug sensitivity by upregulating FOS and CREB5, genes related to longer overall survival in breast cancer patients. Moreover, hyperthermia promoted exosome secretion through Rab7b, a small GTPase that controls endosome transport. The upregulated FOS and CREB5 antioncogenes can be transferred to MCF-7/ADR cells by hyperthermia-treated MCF-7/ADR cell-secreted exosomes. Conclusions Our results demonstrated a novel function of hyperthermia in promoting exosome secretion in adriamycin-resistant breast cancer cells and revealed the effects of hyperthermia on tumor cell biology. These hyperthermia-triggered exosomes can carry antitumor genes to the residual tumor and tumor microenvironment, which may be more beneficial to the effects of hyperthermia. These results represent an exploration of the relationship between therapeutic strategies and exosome biology.

Abstract Background More initial clinical node‐positive breast cancer patients achieve axillary pathological complete response (ax‐pCR) after neoadjuvant systemic therapy (NST). Restaging axillary status and performing de‐escalated surgical procedures to replace routine axillary lymph nodes dissection (ALND) is urgently needed. Targeted axillary lymph node biopsy (TLNB) is a novel de‐escalated surgical strategy marking metastatic axillary nodes before NST and targeted dissection and biopsy intraoperatively to tailor individual axillary management. Methods This study provided a systematic review and meta‐analysis to evaluate the feasibility and diagnosis accuracy of TLNB. Prospective and retrospective clinical trials on TLNB were searched from Pubmed, Embase, and Cochrane. Identification rate (IFR), false‐negative rate (FNR), negative predictive value (NPV), and rate of ax‐pCR were the outcomes of this meta‐analysis. Results One thousand nine hundred and twenty patients attempted TLNB, with an overall IFR of 93.5% (95% confidence interval [CI] 90.1%–96.2%). IFR of three nodal marking methods, namely iodine seeds, clips, and carbon dye, was 95.6% (95% CI 91.2%–98.7%), 91.7% (95% CI 87.3%–95.4%), and 97.1% (95% CI 89.1%–100.0%), respectively. Of them, 847 patients received ALND, with an overall FNR of 5.5% (95% CI 3.3%–8.0%), and NPV ranged from 90.1% to 96.1%. Regression analysis showed that the overlap of targeted and sentinel biopsied nodes might associate with IFRs and FNRs. Conclusion TLNB is a novel, less invasive surgical approach to distinguish initial node‐positive breast cancer that achieves negative axillary conversion after NST. It yields an excellent IFR with a low FNR and a high NPV. A combination of preoperative imaging, intraoperative TLNB with SLNB, and postoperative nodal radiotherapy might affect the future treatment paradigm of primary breast cancer with nodal metastases.

Abstract Recurrence, metastasis, and drug resistance are still big challenges in breast cancer therapy. Internal and external stresses have been proven to substantially facilitate breast cancer progression through molecular and systemic mechanisms. For example, endoplasmic reticulum stress (ERS) results in activation of the unfolded protein response (UPR), which are considered an important cellular stress response. More and more reports indicate its key role in protein homeostasis and other diverse functions involved in the process of breast cancer progression. Therefore, therapies targeting the activation of ERS and its downstream signaling pathways are potentially helpful and novel tools to counteract and fight breast cancer. However, recent advances in our understanding of ERS are focused on characterizing and modulating ERS between healthy and disease states, and so little attention has been paid to studying the role and clinical application of targeting ERS in a certain cancer. In this review, we summarize the function and main mechanisms of ERS in different molecular types of breast cancer, and focus on the development of agents targeting ERS to provide new treatment strategies for breast cancer. Video Abstract

Soil organic carbon (SOC) constitutes a critical component of carbon reservoirs within terrestrial ecosystems. The ramifications of urban land use transitions on SOC dynamics, particularly in rapidly urbanizing regions such as Shanghai, remain insufficiently elucidated. This investigation synergizes a predictive land use change model (Logistic-CA-Markov) with an ecosystem service quantification framework (InVEST), aiming to delineate the interplay between SOC variability and Land Use and Land Cover Change (LUCC) under natural development and ecological protection scenarios. Empirical observations from 2010 to 2020 reveal a contraction in Shanghai’s agricultural land of 34,912.76 hectares, juxtaposed with an expansion of urban built-up areas of 36,048.24 hectares. Projections for 2030 under an ecological protection scenario indicate a moderated urban sprawl, reducing built-up area expansion by 13,518 hectares relative to the natural development scenario. Notably, the net carbon sequestration capacity of Shanghai is anticipated to diminish by approximately 0.418 million tons between 2020 and 2030. This trend is observed under both considered scenarios, forecasting a cumulative reduction in SOC stocks exceeding 1 million tons by 2030. The natural development pathway portends a more pronounced and accelerated depletion of SOC reserves. Although ecological conservation measures show the potential to decelerate this loss, they appear insufficient to reverse the ongoing decline in SOC stocks. This study advocates for strategic urban planning interventions focused on constraining the growth of building densities and augmenting the preservation and management of eco-lands. Such measures are imperative for bolstering Shanghai’s carbon sequestration capacity.

Since the discovery of classical chiral oxazoline ferrocene ligands in 1995, they have become pivotal in transition metal-catalyzed asymmetric transformations. Over the past decade, a notable evolution has been observed with the emergence of siloxane-substituted oxazoline ferrocenes, demonstrating significant potential as chiral ligands and catalysts. These compounds have consistently delivered exceptional results in diverse and mechanistically distinct transformations, surpassing the capabilities of classical oxazoline ferrocene ligands. This review meticulously delineates the research progress on siloxane-substituted oxazoline ferrocene compounds. It encompasses the synthesis of crucial precursors and desired products, highlights their achievements in asymmetric catalysis reactions, and delves into the exploration of the derivatization of these compounds, emphasizing the introduction of ionophilic groups and their impact on the recovery of transition metal catalysts. In addition to presenting the current state of knowledge, this review propels future research directions by identifying potential topics for further investigation concerning the siloxane-tagged derivatives. These derivatives are poised to be promising candidates for the next generation of highly efficient ligands and catalysts.

The average daily weight gain (ADG) is considered a crucial indicator for assessing growth rates in the swine industry. Therefore, investigating the gastrointestinal microbiota and serum metabolites influencing the ADG in pigs is pivotal for swine breed selection. This study involved the inclusion of 350 purebred Yorkshire pigs (age: 90 ± 2 days; body weight: 41.20 ± 4.60 kg). Concurrently, serum and fecal samples were collected during initial measurements of blood and serum indices. The pigs were categorized based on their ADG, with 27 male pigs divided into high-ADG (HADG) and low-ADG (LADG) groups based on their phenotype values. There were 12 pigs in LADG and 15 pigs in HADG. Feces and serum samples were collected on the 90th day. Microbiome and non-targeted metabolomics analyses were conducted using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Pearson correlation, with Benjamini–Hochberg (BH) adjustment, was employed to assess the associations between these variables. The abundance of Lactobacillus and Prevotella in LADG was significantly higher than in HADG, while Erysipelothrix, Streptomyces, Dubosiella, Parolsenella, and Adlercreutzia in LADG were significantly lower than in HADG. The concentration of glutamine, etiocholanolone glucuronide, and retinoyl beta-glucuronide in LADG was significantly higher than in HADG, while arachidonic acid, allocholic acid, oleic acid, phenylalanine, and methyltestosterone in LADG were significantly lower than in HADG. The Lactobacillus–Streptomyces networks (Lactobacillus, Streptomyces, methyltestosterone, phenylalanine, oleic acid, arachidonic acid, glutamine, 3-ketosphingosine, L-octanoylcarnitine, camylofin, 4-guanidinobutyrate 3-methylcyclopentadecanone) were identified as the most influential at regulating swine weight gain. These findings suggest that the gastrointestinal tract regulates the daily weight gain of pigs through the network of Lactobacillus and Streptomyces. However, this study was limited to fecal and serum samples from growing and fattening boars. A comprehensive consideration of factors affecting the daily weight gain in pig production, including gender, parity, season, and breed, is warranted.

As one of the most critical economic traits, the litter performance of sows is influenced by their parity. Some studies have indicated a connection between the gut microbiota and the litter performance of animals. In this study, we examined litter performance in 1363 records of different parities of Large White sows. We observed a marked decline in TNB (Total Number Born) and NBH (Number of Healthy Born) We observed a marked decline in TNB (Total Number Born) and NBH (Number of Healthy Born) among sows with parity 7 or higher. To gain a deeper understanding of the potential role of gut microbiota in this phenomenon, we conducted 16S rRNA amplicon sequencing of fecal DNA from 263 Large White sows at different parities and compared the changes in their gut microbiota with increasing parity. The results revealed that in comparison to sows with a parity from one to six, sows with a parity of seven or higher exhibited decreased alpha diversity in their gut microbiota. There was an increased proportion of pathogenic bacteria (such as Enterobacteriaceae, Streptococcus, and Escherichia–Shigella) and a reduced proportion of SCFA-producing families (such as Ruminococcaceae), indicating signs of inflammatory aging. The decline in sow function may be one of the primary reasons for the reduction in their litter performance.

Abstract Background Retinitis pigmentosa is a rod-cone degenerative disease that induces irreversible vision loss. This study probed the protective capacity of mesenchymal stem cell-derived small EVs (MSC-EVs) on the retinas of rd10 mice and the underlying mechanism. Methods MSC-EVs were injected into the vitreous of rd10 mice at postnatal day 14 and P21; morphology and function were examined at P28. The mechanism of action was explored by using co-culture of photoreceptor cell line 661 W and microglia cell line BV2. Results Treatment with MSC-EVs increased the survival of photoreceptors and preserved their structure. Visual function, as reflected by optomotor and electroretinogram responses, was significantly enhanced in MSC-EVs-treated rd10 mice. Mechanistically, staining for Iba1, GFAP, F4/80, CD68 and CD206 showed that MSC-EVs suppressed the activation of microglial, Müller glial and macrophages. Furthermore, western blotting showed that the treatment inhibited the NF-κB pathway. RNA-seq and qPCR showed that MSC-EVs upregulated anti-inflammatory cytokines while downregulating pro-inflammatory cytokines. MSC-EVs application in vitro decreased the number of TUNEL-positive 661 W cells co-cultured with LPS-stimulated BV2, with similar impact on the cytokine expression as in vivo study. Genetic screening predicted miR-146a to be the downstream target of MSC-EVs, which was detected in MSC-EVs and upregulated in co-cultured 661 W cells and BV2 cells after MSC-EVs treatment. Upregulation of miR-146a by using its mimic decreased the expression of the transcription factor Nr4a3, and its downregulation inhibition promoted Nr4a3 expression in both 661 W and BV2 cells. Nr4a3 was further identified as the target gene of miR-146a by dual-luciferase assay. Furthermore, overexpressing miR-146a significantly decreased the expression of LPS-induced pro-inflammatory cytokines in BV2 cells. Conclusions MSC-EVs delays retinal degeneration in rd10 mice mainly by its anti-inflammatory effect via the miR-146a-Nr4a3axis. Hence, MSC-EVs may be used in the treatment of neurodegenerative diseases.

Abstract Background Bama miniature pigs aged between six (6 M) and twelve months (12 M) are usually used in human medical research as laboratory pigs. However, the difference in serum metabolic profiles from 6 to 12 M-old pigs remains unclear. This study aimed to identify the metabolic and physiological profiles present in the blood to further explain changes in Bama miniature pig growth. We collected blood samples from 6 M-, eight-month- (8 M-), ten-month- (10 M-), and 12 M-old healthy Guangxi Bama miniature pigs. A total of 20 blood physiological indices (BPIs) were measured: seven for white blood cells, eight for red blood cells, and five for platelet indices. Liquid chromatography and mass spectrometry-based non-targeted metabolomic approaches were used to analyze the difference in metabolites. The associations between the differences were calculated using Spearman correlations with Benjamini–Hochberg adjustment. The 100 most abundant differential metabolites were selected for analysis of their metabolic profiles. Results There were no significant differences in BPIs at different ages, but the mid cell ratio and red blood cell number increased with age. Seven BPIs in Bama miniature pigs were closer to human BPIs than to mouse BPIs. A total of 14 and 25 significant differential metabolites were identified in 6 M vs. 12 M and 8 M vs. 12 M, respectively. In total, 9 and 18 amino acids and their derivatives showed significantly lower concentrations in 6 M- and 8 M-old pigs than in 12 M-old pigs. They were identified as the core significantly different metabolites between the age groups 6 M vs. 12 M and 8 M vs. 12 M. Half of the enriched pathways were the amino acids metabolism pathways. The concentration of six amino acids (dl-tryptophan, phenylacetylglycine, muramic acid, N-acetylornithine, l(−)-pipecolinic acid, and creatine) and their derivatives increased with age. A total of 61 of the top 100 most abundant metabolites were annotated. The metabolic profiles contained 14 amino acids and derivatives, six bile acids and derivatives, 19 fatty acids and derivatives, and 22 others. The concentrations of fatty acids and derivatives were found to be inversely proportional to those of amino acids and derivatives. Conclusion These findings suggest high levels of MID cell ratio, red blood count, and amino acids in 12 M-old pigs as indicators for improved body function over time in Bama miniature pigs, similar to those in human development. This makes the pig a more suitable medical model organism than the mouse. The results of this study are limited to the characteristics of blood metabolism in the inbred Bama miniature pigs, and the effects of impacting factors such as breed, age, sex, health status and nutritional level should be considered when studying other pig populations.

Abstract Universities are increasingly using learning communities (LCs) to promote the academic and social integration of entering students, especially within STEM majors. Examining the causal effect of LCs on student networks is necessary to understand the nature and scope of their impact. This study combines a regression discontinuity design with social network analysis to estimate the effect of a simple LC design on the size, strength, structure, and composition of friendship networks among students within the same biological sciences freshman cohort. Results of the quasi-experimental analysis indicate that LC participants acquired one additional friend in the major and increased their share of friends in the LC by 54 percentage-points. Exponential random-graph models that test mediation and alternative friendship mechanisms provide support for the theoretical argument that the LC promoted friendship development by structuring opportunities for interaction through block-registration into courses. Thus, this study shows that even simple LCs can shape the development of friendships through relatively low-cost administrative means. The increased access to resources and support facilitated by the LC is likely beneficial for participating students. However, there is a potential downside when eligibility for participation is determined using academic metrics that separate the student population into distinct classroom environments.

Vibrio vulnificus can cause disease in aquatic animals and humans, therefore, rapid and simple field detection of pathogenic V. vulnificus is important for early disease prevention. In this study, a novel recombinase-aided amplification (RAA) combined test strip with double T-lines (RAA-TS-DTL) was developed for the rapid detection of V. vulnificus in aquatic products. Pathogenic V. vulnificus was detected using the virulence vvhA gene and the housekeeping gene gyrB gene as the dual target of the test strip. The RAA-TS-DTL method showed 100% specificity for V. vulnificus, and no cross-reaction was observed with Vibrio spp. or other bacteria (n = 14). Furthermore, sensitive detection of V. vulnificus in oysters was achieved. The LODs of the gyrB and vvhA genes were 6 CFU/mL and 23 CFU/mL, respectively, which was about five times higher than that of the commercial test strip. The method was validated with spiked samples (n = 60) of fish, shrimp and oyster. The consistency between RAA-TS-DTL and the traditional culture method was 97.9%. In addition, the entire process of detection, including preparation of the sample, could be completed within 50 min. Our results indicated that the developed RAA-TS-DTL was a reliable and useful tool for rapid screening or on-site detection of pathogenic V. vulnificus in aquatic products and aquaculture water.