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Zhi-Hang Chen,1,&ast; Qian Zhou,2,&ast; Ze-Bin Chen,1,&ast; Wen-Xuan Xie,1 Zi-Min Song,1 Shui-Rong Lin,1 Wei Wang,3 Shun-Li Shen,1 Ming Kuang1 1Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Division of Interventional Ultrasound, Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shun-Li Shen; Ming Kuang, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86 20-87755766, Email shenshli@mail.sysu.edu.cn; kuangm@mail.sysu.edu.cnPurpose: Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients.Patients and Methods: This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences.Results: Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population.Conclusion: In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.Keywords: hepatocellular carcinoma, laparoscopic liver resection, generalized propensity score analysis, overlap weighting, clinical outcome

Pei-Jian Peng,1,* Hua Cheng,2,* Xue-Qing Ou,3 Lin-Juan Zeng,1 Xuan Wu,4 Yu-Meng Liu,5 Zhong Lin,1 Yan-Na Tang,1 Si-Yang Wang,3 Hong-Yu Zhang,1 Zhi-Bin Chen3 1Department of Medical Oncology, 2Department of Surgical Oncology, 3Department of Radiation Oncology, The Fifth Affiliated Hospital of Sun-Yat-Sen University, Zhu Hai, Guangdong Province, People's Republic of China; 4Department of Medical Oncology, Cancer Center, Sun-Yat-Sen University, Guangzhou, People's Republic of China; 5Department of Oncology, the People's Hospital of Zhongshan City, Zhongshan, Guangdong Province, People's Republic of China *These authors contributed equally to this work Purpose: This retrospective study evaluates the efficacy and safety of S-1 chemotherapy for recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy. Patients and methods: Thirty-nine patients with recurrent and metastatic nasopharyngeal carcinoma who failed previous platinum-based chemotherapy received oral S-1 chemotherapy (twice daily from day 1 to 14) every 3 weeks. The dose of S-1 was determined according to the body surface area (BSA): 40 mg twice a day for BSA

The objective of this study was to investigate the expressions of angiogenic factors and elucidate their angiogenic and prognostic roles in hepatocellular carcinoma (HCC) with background of hepatitis B virus (HBV). We evaluated microvessel density (MVD) of HCC, and investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and matrix metalloproteinases-9 (MMP-9) in 67 specimens of surgically resected HCC, which were all positive for hepatitis B surface antigen. We investigated the relationship between their expressions and clinicopathological factors or prognosis. The microvessel density (MVD) of tumor tissue and surrounding normal liver tissue was 93.1 +/- 43.8/mm2 and 30.4 +/- 14.8/mm2, respectively. The MVD of well-differentiated HCC was significantly less than that of poorly differentiated HCC. MVD was positively correlated with VEGF and Ang-2 expression (P = 0.0023 and 0.0265, respectively). There was less tumor recurrence in low Ang-2 and low MMP-9 group than high Ang-2 and/or high MMP-9 group (P = 0.002). In Cox regression model, portal vein thrombus and intrahepatic metastasis was the risk factors of tumor recurrence (P = 0.003 and 0.001, respectively). Our study showed that the expression of VEGF and Ang-2 were positively correlated with MVD. Ang-2 expression and/or MMP-9 expression might be a significant predictive factor for recurrence after resection in HCC patients with the background of HBV. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) and their alternatives (e.g., dechlorane plus (DPs) and decabromodiphenyl ethane (DBDPE)) are ubiquitous in various environmental media. However, limited data is available on these chemicals in edible fish species from the wide-open South China Sea (SCS). In the present study, ten legacy PBDEs and three substitutions (DBDPE and two DPs) were analyzed in 16 wild fish species sampled from the open SCS to investigate their spatial and species-specific variations. The results showed that the total concentrations of PBDEs, DBDPE, and DPs in fish samples were in the range of 1.69-47.6, not detected (nd) to 21.0, and nd to 3.80 ng/g lipid weight (lw), respectively. BDEs 47, 209 and 100 were the dominant target PBDE congeners, representing 49.2%, 17.2% and 9.93% of the total PBDE concentrations, respectively. Higher concentrations of PBDEs, DBDPE, and DPs were found in fish species from the Wanshan Archipelago compared to those from the Mischief Reef and the Yongxing Island, suggesting the significant influence of anthropogenic activities. Species-specific differences in levels of PBDEs were observed, with the order of bathydemersal > demersal > pelagic ≈ reef-associated > benthopelagic species. The average f anti value of all fish samples was 0.68, suggesting commercial DP products as a contamination source. The levels of PBDEs, DPs, and DBDPE in fish samples were relatively low compared with those from other locations around the globe. Finally, the health risks concerning the ingestion of BDEs 47, 99, 153 and 209 via fish consumption collected from the SCS are negligible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A full-fledged quantum network relies on the formation of entangled links between remote location with the help of quantum repeaters. The famous Duan-Lukin-Cirac-Zoller quantum repeater protocol is based on long distance single-photon interference, which not only requires high phase stability but also cannot generate maximally entangled state. Here, we propose a quantum repeater protocol using the idea of post-matching, which retains the same efficiency as the single-photon interference protocol, reduces the phase-stability requirement and can generate maximally entangled state in principle. We also outline an implementation of our scheme based on the Kerr nonlinear resonator. Numerical simulations show that our protocol has its superiority by comparing with existing protocols under a generic noise model and show the feasibility of building a large-scale quantum communication network with our scheme. We believe our work represents a crucial step towards the construction of a fully-connected quantum network., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Cervical cancer (CCa) patients with lymph node (LN) metastasis face poor prognoses and have limited treatment options. Aberrant N6-methyladenosine (m 6 A) modification of RNAs are known to promote tumor metastasis, but their role in CCa remains unclear. Our study reveals that HNRNPC, an alternative splicing (AS) factor and m 6 A reader, increases tumor-related variants through m 6 A-dependent manner, thereby promoting lymphatic metastasis in CCa. We found that HNRNPC overexpression correlates with lymphatic metastasis and poorer prognoses in CCa patients. Functionally, knocking down HNRNPC markedly inhibited the migration and invasion of several CCa cell lines, while supplementing HNRNPC restored the malignant phenotypes of these cells. Mechanistically, HNRNPC regulates exon skipping of FOXM1 by binding to its m6A-modified motif. Mutating the m 6 A site on FOXM1 weakened the interaction between HNRNPC and FOXM1 pre-RNA, leading to a reduction in the metastasis-related FOXM1-S variant. In conclusion, our findings demonstrate that m 6 A-dependent alternative splicing mediated by HNRNPC is essential for lymphatic metastasis in CCa, potentially providing novel clinical markers and therapeutic strategies for patients with advanced CCa., (© 2024. The Author(s).)

Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100 β , neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100 β ), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100 β , and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Red tides are a type of natural marine disaster caused by harmful algae characterized by a high toxicity, wide distribution, and long duration. Since the concentration of algal toxins in seawater increases with the occurrence of red tides, algal toxins detected in seawater could be used to predict the occurrence and evolution of red tides. Brevetoxin-A (BTX-A) is a secondary metabolite produced by the harmful algae Karenia brevis , whose detection in seawater could form the basis of an accurate warning system for incoming red tides. However, due to the inherent complexity of the seawater matrix and the extremely low levels of BTX-A in seawater, the use of instruments for its direct detection is difficult. Therefore, there is an urgent need to develop a sample pretreatment method for the efficient enrichment of BTX-A in seawater. In this study, a metal-organic backbone material (UiO-66) and its composite with silica microspheres (SiO 2 @UiO-66) were successfully synthesized using the solvothermal method. The prepared SiO 2 @UiO-66 exhibited good hydrophilicity, water stability, and large specific surface area. Furthermore, it also exhibited hydrogen bonding and electrostatic interactions with BTX-A, had a strong affinity for BTX-A, and was able to efficiently adsorb BTX-A in complex matrices. Therefore, SiO 2 @UiO-66 showed potential as a novel packing material for the extraction of BTX-A from solid phase extraction columns. Combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), a highly sensitive detection method for the determination of BTX-A in marine water was established. The established analytical method had a low detection limit (3.0 pg/mL), a wide linear range (10.0 -200.0 pg/mL), and a good linear relationship ( R =0.9992). Combined with the Fujian Province Red Tide Monitoring and Early Warning Information 2021 issued by the Fujian Provincial Oceanic and Fisheries Bureau, the analytical method established herein was successfully applied to analyze and monitor the content of BTX-A in actual seawater samples. This highlights the proposed system's potential for use as an early warning factor in the monitoring of red tides, representing a simple and fast pretreatment methodology for the detection of BTX-A in seawater.

Introduction: Comparative studies on surgical treatments with time-to-event endpoints have provided substantial evidence for clinical practice, but the accurate use of survival data analysis and the control of confounding bias remain big challenges., Methods: This was a survey of surgical studies with survival outcomes published in four general medical journals and five general surgical journals in 2021. The two most concerned statistical issues were evaluated, including confounding control by propensity score analysis (PSA) or multivariable analysis and testing of proportional hazards (PH) assumption in Cox model., Results: A total of 74 studies were included, comprising 63 observational studies and 11 randomized controlled trials. Among the observational studies, the proportion of studies utilizing PSA in surgical oncology and non-oncology studies was similar (40.9 % versus 36.8 %, P = 0.762). However, the former reported a significantly lower proportion of PH assumption assessments compared to the latter (13.6 % versus 42.1 %, P = 0.020). Twenty-five observational studies (25/63) used PSA methods, but two-thirds of them (17/25) showed unclear balance of baseline data after PSA. And the proportion of PH assumption testing after PSA was slightly lower than that before PSA, but the difference was not statistically significant (24.0 % versus 28.0 %, P = 0.317). Comprehensive suggestions were given on confounding control in survival analysis and alternative resolutions for non-compliance with PH assumption., Conclusion: This study highlights suboptimal reporting of PH assumption evaluation in observational surgical studies both before and after PSA. Efforts and consensus are needed with respect to the underlying assumptions of statistical methods., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Institutional support is crucial for the successful career advancement of all faculty but in particular those who are women. Evolving from the past, in which gender disparities were prevalent in many institutions, recent decades have witnessed significant progress in supporting the career advancement of women faculty in science and academic medicine. However, continued advancement is necessary as previously unrecognized needs and new opportunities for improvement emerge. To identify the needs, opportunities, and potential challenges encountered by women faculty, the Women's Leadership Committee of the Arteriosclerosis, Thrombosis, and Vascular Biology Council developed an initiative termed GROWTH (Generating Resources and Opportunities for Women in Technology and Health). The committee designed a survey questionnaire and interviewed 19 leaders with roles and responsibilities in faculty development from a total of 12 institutions across various regions of the United States. The results were compiled, analyzed, and discussed. Based on our interviews and analyses, we present the current status of these representative institutions in supporting faculty development, highlighting efforts specific to women faculty. Through the experiences, insights, and vision of these leaders, we identified success stories, challenges, and future priorities. Our article provides a primer and a snapshot of institutional efforts to support the advancement of women faculty. Importantly, this article can serve as a reference and resource for academic entities seeking ideas to gauge their commitment level to women faculty and to implement new initiatives. Additionally, this article can provide guidance and strategies for women faculty as they seek support and resources from their current or prospective institutions when pursuing new career opportunities., Competing Interests: None.

The large-scale deployment of quantum secret sharing (QSS) in quantum networks is currently challenging due to the requirements for the generation and distribution of multipartite entanglement states. Here we present an efficient source-independent QSS protocol utilizing entangled photon pairs in quantum networks. Through the post-matching method, which means the measurement events in the same basis are matched, the key rate is almost independent of the number of participants. In addition, the unconditional security of our QSS against internal and external eavesdroppers can be proved by introducing an equivalent virtual protocol. Our protocol has great performance and technical advantages in future quantum networks.

Objective: Resection of high-grade glioma with sodium fluorescein can improve the resection rate of the glioma and improve survival. However, it is unclear whether the yellow fluorescence boundary of the high-grade glioma is consistent with the actual boundary of the tumor. This study explores the yellow fluorescence boundary and the actual tumor boundary in high-grade glioma surgery., Methods: This is a retrospective analysis of 10 patients with high-grade gliomas who underwent tumor visualization with sodium fluorescein. After staining of the tumor, random selections of both developed and non-developed yellow fluorescent border tissue at the fluorescence chromogenic boundary were made, followed by pathological examination. Claudin-5, an important component of the tight connections between vascular endothelial cells, was assessed by immunohistochemistry and qRT-PCR in the tumor and surrounding tissues in order to determine the tumor cell content of the tissue, blood-brain barrier damage, and vascular proliferation. The yellow fluorescence boundary was compared with the actual tumor boundary and the results analyzed., Results: Tumor cells were still detected outside the yellow fluorescence boundary during high-grade glioma surgery ( P  <  0.05). Claudin-5 expression was higher in high-grade gliomas than in adjacent normal tissues ( P  < 0.05), while disconnected Claudin-5 expression was associated with intraoperative yellow fluorescence imaging ( r  = 0.67)., Conclusions: There is a difference between the yellow fluorescence boundary and the actual boundary of the tumor in high-grade glioma, and there are glioma cell infiltrations in the brain tissue of the undeveloped yellow fluorescent border. To ensure patient recovery and function, it is recommended that tumor resection be expanded based on yellow fluorescence visualization. Claudin-5 is overall up-regulated in high-grade gliomas, but some Claudin-5 expression is disconnected. This Claudin-5 expression pattern may be related to the development of yellow fluorescence.

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti 3 C 2 T x ) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti 3 C 2 T x ) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser 473 ) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN' enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury., (© 2024. The Author(s).)

Diabetes mellitus (DM) is a metabolic disease that heightens the risks of many vascular complications, including peripheral arterial disease (PAD). Various types of cells, including but not limited to endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages (MΦs), play crucial roles in the pathogenesis of DM-PAD. Long non-coding RNAs (lncRNAs) are epigenetic regulators that play important roles in cellular function, and their dysregulation in DM can contribute to PAD. This review focuses on the developing field of lncRNAs and their emerging roles in linking DM and PAD. We review the studies investigating the role of lncRNAs in crucial cellular processes contributing to DM-PAD, including those in ECs, VSMCs, and MΦ. By examining the intricate molecular landscape governed by lncRNAs in these relevant cell types, we hope to shed light on the roles of lncRNAs in EC dysfunction, inflammatory responses, and vascular remodeling contributing to DM-PAD. Additionally, we provide an overview of the research approach and methodologies, from identifying disease-relevant lncRNAs to characterizing their molecular and cellular functions in the context of DM-PAD. We also discuss the potential of leveraging lncRNAs in the diagnosis and therapeutics for DM-PAD. Collectively, this review provides a summary of lncRNA-regulated cell functions contributing to DM-PAD and highlights the translational potential of leveraging lncRNA biology to tackle this increasingly prevalent and complex disease., (© 2024. The Author(s).)

Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.

Quantum conference key agreement (QCKA) enables the unconditional secure distribution of conference keys among multiple participants. Due to challenges in high-fidelity preparation and long-distance distribution of multi-photon entanglement, entanglement-based QCKA is facing severe limitations in both key rate and scalability. Here, we propose a source-independent QCKA scheme utilizing the post-matching method, feasible within the entangled photon pair distribution network. We introduce an equivalent distributing virtual multi-photon entanglement protocol for providing unconditional security proof even in the case of coherent attacks. For the symmetry star network, compared with the previous n-photon entanglement protocol, the conference key rate is improved from O(η n ) to O(η 2 ), where η is the transmittance from the entanglement source to one participant. Simulation results show that the performance of our protocol has multiple orders of magnitude advantages in the intercity distance. We anticipate that our approach will demonstrate its potential in the implementation of quantum networks.

Objectives: To observe the effect of electroacupuncture (EA) stimulation of "Zusanli"(ST36) and"Xuehai"(SP10) on the angiogenesis of the local injured skin tissue in mice with psoriasis, so as to explore its mechanisms underlying improvement of psoriasis-induced skin lesions., Methods: A total of 24 female BALB/c mice aged 6-8 weeks were randomly divided into control, model and EA groups, with 8 mice in each group. The psoriasis-like skin lesion model was established by application of 5% imiquimod (IMQ) cream to the mice's back skin, 62.5 mg/d, for 7 days after local depilation, and the mice of the control group received local application of an equal amount of petroleum jelly once a day for 7 days. EA stimulation (2 Hz/100 Hz) was applied to ST36 and SP10 for 30 min, once daily for 7 consecutive days. Photos of the topical injured skin at the back were taken every day, and the severity of psoriasis lesions (psoriasis area and severity index ［PASI］) was scaled. Following H.E. staining, the morphological changes in the injured skin tissue were observed with epidermal thickness analyzed, and the Masson staining was used to observe the proportion of collagen fibers in the injured skin tissues. Immunohistochemical method was used to detect the expression of microvascular markers CD31 and vascular endothelial growth factor (VEGF) and the microvascular density (MVD) was calculated. Western blot was used to detect the expression levels of CD31, VEGF proteins and mitogen activated protein kinases (MAPK) signaling pathway related proteins p38, phosphorylated p38 (p-p38), extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK) and p-JNK in the injured skin tissue., Results: Compared with the control group, the mice in the model group showed an evident increase in the erythema score, scales score, skin thickening score and PASI score, epidermal thickness, proportion of the collagen fibers, MVD value of CD31 and VEGF, and expression levels of CD31 and VEGF proteins, and p-p38/p38, p-ERK/ERK and p-JNK/JNK ratios in the injured skin tissue ( P <0.001, P <0.01). In contrast to the model group, the EA group had a significant decrease in the levels of all the indexes mentioned above ( P <0.05, P <0.01, P <0.001)., Conclusions: EA intervention can improve the psoriasis-like skin lesions induced by IMQ in mice, which may be related with its functions in down-regulating the expression of angiogenic related factors CD31 and VEGF proteins and MAPK signaling pathway related proteins in the topical injured skin tissue.

The pancreas is a vital organ for maintaining metabolic balance within the body, in part due to its production of metabolic hormones such as insulin and glucagon, as well as digestive enzymes. The pancreas is also a highly vascularized organ, a feature facilitated by the intricate network of pancreatic capillaries. This extensive capillary network is made up of highly fenestrated endothelial cells (ECs) important for pancreas development and function. Accordingly, the dysfunction of ECs can contribute to that of the pancreas in diseases like diabetes and cancer. Thus, researching the function of pancreatic ECs (pECs) is important not only for understanding pancreas biology but also for developing its pathologies. Mouse models are valuable tools to study metabolic and cardiovascular diseases. However, there has not been an established protocol with sufficient details described for the isolation of mouse pECs due to the relatively small population of ECs and the abundant digestive enzymes potentially released from the acinar tissue that can lead to cell damage and, thus, low yield. To address these challenges, we devised a protocol to enrich and recover mouse pECs, combining gentle physical and chemical dissociation and antibody-mediated selection. The protocol presented here provides a robust method to extract intact and viable ECs from the whole mouse pancreas. This protocol is suitable for multiple downstream assays and may be applied to various mouse models.

Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia . This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species., Competing Interests: Competing interests statement:The authors declare no competing interest.

Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Fish are vital in river ecosystems; however, traditional investigations of fish usually cause ecological damage. Extracting DNA from aquatic environments and identifying DNA sequences offer an alternative, noninvasive approach for detecting fish species. In this study, the effects of environmental DNA (eDNA), coupled with PCR and next-generation sequencing, and electrofishing for identifying fish community composition and diversity were compared. In three subtropical rivers of southern China, fish specimens and eDNA in water were collected along the longitudinal (upstream-downstream) gradient of the rivers. Both fish population parameters, including species abundance and biomass, and eDNA OTU richness grouped 38 sampling sites into eight spatial zones with significant differences in local fish community composition. Compared with order-/family-level grouping, genus-/species-level grouping could more accurately reveal the differences between upstream zones I-III, midstream zones IV-V, and downstream zones VI-VIII. From the headwaters to the estuary, two environmental gradients significantly influenced the longitudinal distribution of the fish species, including the first gradient composed of habitat and physical water parameters and the second gradient composed of chemical water parameters. The high regression coefficient of alpha diversity between eDNA and electrofishing methods as well as the accurate identification of dominant, alien, and biomarker species in each spatial zone indicated that eDNA could characterize fish community attributes at a level similar to that of traditional approaches. Overall, our results demonstrated that eDNA metabarcoding can be used as an effective tool for revealing fish composition and diversity, which is important for using the eDNA technique in aquatic field monitoring., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The trees of the Dongzhai Harbor mangrove forest suffer from antibiotic contamination from surrounding aquaculture areas. Despite this being one of the largest mangrove forests in China, few studies have focused on the antibiotic pollution status in these aquaculture areas. In the present study, the occurrence, distribution, and risk assessment of 37 antibiotics in surface water and sediment samples from aquaculture areas around Dongzhai Harbor mangrove forests were analyzed. The concentration of total antibiotics (∑antibiotics) ranged from 78.4 ng/L to 225.6 ng/L in surface water (except S14-A2) and from 19.5 ng/g dry weight (dw) to 229 ng/g dw in sediment. In the sediment, the concentrations of ∑antibiotics were relatively low (19.5-52.3 ng/g dw) at 75 % of the sampling sites, while they were high (95.7-229.0 ng/g dw) at a few sampling sites (S13-A1, S13D, S8D). The correlation analysis results showed that the K d values of the 9 antibiotics were significantly positively correlated with molecular weight (MW), K ow , and LogK ow . Risk assessment revealed that sulfamethoxazole (SMX) in surface water and SMX, enoxacin (ENX), ciprofloxacin (CFX), enrofloxacin (EFX), ofloxacin (OFX), and norfloxacin (NFX) in sediment had medium/high risk quotients (RQs) at 62.5 % and 25-100 %, respectively, of the sampling sites. The antibiotic mixture in surface water (0.06-3.36) and sediment (0.43-309) posed a high risk at 37.5 % and 66.7 %, respectively, of the sampling sites. SMX was selected as an indicator of antibiotic pollution in surface water to assist regulatory authorities in monitoring and managing antibiotic pollution in the aquaculture zone of Dongzhai Harbor. Overall, the results of the present study provide a comprehensive and detailed analysis of the characteristics of antibiotics in the aquaculture environment around the Dongzhai Harbor mangrove system and provide a theoretical basis for the source control of antibiotics in mangrove systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atherosclerosis, a chronic inflammatory disease, is the primary cause of myocardial infarction and ischemic stroke. Recent studies have demonstrated that dysregulation of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) contributes to plaque development, making YAP/TAZ potential therapeutic targets. However, systemic modulation of YAP/TAZ expression or activities risks serious off-target effects, limiting clinical applicability. To address the challenge, this study develops monocyte membrane-coated nanoparticles (MoNP) as a targeted delivery system for activated and inflamed endothelium lining the plaque surface. The MoNP system is used to deliver verteporfin (VP), aimed at inhibiting YAP/TAZ specifically within arterial regions prone to atherosclerosis. The results reveal that MoNP significantly enhance payload delivery to inflamed endothelial cells (EC) while avoiding phagocytic cells. When administered in mice, MoNP predominantly accumulate in intima of the atheroprone artery. MoNP-mediated delivery of VP substantially reduces YAP/TAZ expression, thereby suppressing inflammatory gene expression and macrophage infiltration in cultured EC and mouse arteries exposed to atherogenic stimuli. Importantly, this targeted VP nanodrug effectively decreases plaque development in mice without causing noticeable histopathological changes in major organs. Collectively, these findings demonstrate a lesion-targeted and pathway-specific biomimetic nanodrug, potentially leading to safer and more effective treatments for atherosclerosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kuei-Chun Wang reports financial support was provided by National Institutes of Health and American Heart Association., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Extracellular vesicles (EVs) are considered to be a new generation of bioinspired nanoscale drug delivery systems due to their low immunogenicity, natural functionality, and excellent biocompatibility. However, limitations such as low uptake efficiency, insufficient production, and inhomogeneous performance undermine their potential. To address these issues, numerous researchers have put forward various methods and applications for enhancing EV uptake in recent decades. In this review, we introduce various methods for the cellular uptake of EVs and summarize recent advances on the methods and mechanisms for enhancing EV uptake. In addition, we provide further understanding regarding enhancing EV uptake and put forward prospects and challenges for the development of EV-based therapy in the future., (© 2024. Huazhong University of Science and Technology.)

Objectives: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images., Methods: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed., Results: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001)., Conclusions: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis., (© 2024. The Author(s).)

Flow patterns exert significant effects on vascular endothelial cells (ECs) to lead to the focal nature of atherosclerosis. Using a step flow chamber to investigate the effects of disturbed shear (DS) and pulsatile shear (PS) on ECs in the same flow channel, we conducted single-cell RNA sequencing analyses to explore the distinct transcriptomic profiles regulated by DS vs. PS. Integrated analysis identified eight cell clusters and demonstrated that DS induces EC transition from atheroprotective to proatherogenic phenotypes. Using an automated cell type annotation algorithm (SingleR), we showed that DS promoted endothelial-to-mesenchymal transition (EndMT) by inducing the transcriptional phenotypes for inflammation, hypoxia responses, transforming growth factor-beta (TGF-β) signaling, glycolysis, and fatty acid synthesis. Enolase 1 (ENO1), a key gene in glycolysis, was one of the top-ranked genes in the DS-induced EndMT cluster. Pseudotime trajectory analysis revealed that the kinetic expression of ENO1 was significantly associated with EndMT and that ENO1 silencing repressed the DS- and TGF-β-induced EC inflammation and EndMT. Consistent with these findings, ENO1 was highly expressed in ECs at the inner curvature of the mouse aortic arch (which is exposed to DS) and atherosclerotic lesions, suggesting its proatherogenic role in vivo. In summary, we present a comprehensive single-cell atlas of ECs in response to different flow patterns within the same flow channel. Among the DS-regulated genes, ENO1 plays an important role in DS-induced EC inflammation and EndMT. These results provide insights into how hemodynamic forces regulate vascular endothelium in health and disease., Competing Interests: Competing interests statement:The authors declare no competing interest.

E-commerce, a type of trading that occurs at a high frequency on the internet, requires guaranteeing the integrity, authentication, and nonrepudiation of messages through long distance. As current e-commerce schemes are vulnerable to computational attacks, quantum cryptography, ensuring information-theoretic security against adversary's repudiation and forgery, provides a solution to this problem. However, quantum solutions generally have much lower performance compared to classical ones. Besides, when considering imperfect devices, the performance of quantum schemes exhibits a notable decline. Here, we demonstrate the whole e-commerce process of involving the signing of a contract and payment among three parties by proposing a quantum e-commerce scheme, which shows resistance of attacks from imperfect devices. Results show that with a maximum attenuation of 25 dB among participants, our scheme can achieve a signature rate of 0.82 times per second for an agreement size of approximately 0.428 megabit. This proposed scheme presents a promising solution for providing information-theoretic security for e-commerce.

Peripheral arterial disease (PAD) represents a global health concern with a rising prevalence attributed to factors such as obesity, diabetes, aging, and smoking. Among patients with PAD, chronic limb-threatening ischemia (CLTI) is the most severe manifestation, associated with substantial morbidity and mortality. While revascularization remains the primary therapy for CLTI, not all patients are candidates for such interventions, highlighting the need for alternative approaches. Impaired angiogenesis, the growth of new blood vessels, is a central feature of PAD, and despite decades of research, effective clinical treatments remain elusive. Epigenetics, the study of heritable changes in gene expression, has gained prominence in understanding PAD pathogenesis. Here, we explore the role of epigenetic regulation in angiogenesis within the context of PAD, with a focus on long non-coding RNAs and fibroblast-endothelial cell transdifferentiation. Additionally, we discuss the interplay between metabolic control and epigenetic regulation, providing insights into potential novel therapeutic avenues for improving PAD treatments. This review aims to offer a concise update on the application of epigenetics in angiogenesis and PAD research, inspiring further investigations in this promising field., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Objective: Gastric cancer (GC) ranks fifth in incidence and fourth for mortality worldwide. The response to immune checkpoint blockade (ICB) therapy in GC is heterogeneous due to tumour-intrinsic and acquired immunotherapy resistance. We developed an immunophenotype-based subtyping of human GC based on immune cells infiltration to develop a novel treatment option., Design: A algorithm was developed to reclassify GC into immune inflamed, excluded and desert subtypes. Bioinformatics, human and mouse GC cell lines, syngeneic murine gastric tumour model, and CTLA4 blockade were used to investigate the immunotherapeutic effects by restricting receptor tyrosine kinase (RTK) signalling in immune desert (ICB-resistant) type GC., Results: Our algorithm restratified subtypes of human GC in public databases and showed that immune desert-type and excluded-type tumours are ICB-resistant compared with immune-inflamed GC. Moreover, epithelial-mesenchymal transition (EMT) signalling was highly enriched in immune desert-type GC, and syngeneic murine tumours exhibiting mesenchymal-like, compared with epithelial-like, properties are T cell-excluded and resistant to CTLA4 blockade. Our analysis further identified a panel of RTKs as potential druggable targets in the immune desert-type GC. Dovitinib, an inhibitor of multiple RTKs, strikingly repressed EMT programming in mesenchymal-like immune desert syngeneic GC models. Dovitinib activated the tumour-intrinsic SNAI1/2-IFN-γ signalling axis and impeded the EMT programme, converting immune desert-type tumours to immune inflamed-type tumours, sensitising these mesenchymal-like 'cold' tumours to CTLA4 blockade., Conclusion: Our findings identified potential druggable targets relevant to patient groups, especially for refractory immune desert-type/ 'cold' GC. Dovitinib, an RTK inhibitor, sensitised desert-type immune-cold GC to CTLA4 blockade by restricting EMT and recruiting T cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

An efficient palladium-catalyzed enantioselective direct N -alkylation of indoles using a novel type of axially chiral styrene-phosphine ligand SJTU-PHOS-1 was developed. This reaction demonstrated good functional group compatibility and a wide range scope of substrates in mild conditions. Moreover, the DFT calculations expounded the coordination mode of the metal catalyst and the axially chiral styrene-phosphine ligand in the enantioselectivity control.

Some organic dyes and photosensitizers with strong visible absorption can behave as photo-responsive oxidase mimics. However, the relationship between the photo-oxidase activity and molecular structure remains unclear to date. In this work, a new type of photosensitizer with the characteristics of molecular rotors, namely DPPy, served as the molecular scaffold for further investigation. To adjust the photocatalytic oxidation ability, DAPy and CBPy were designed and synthesized based on the enhancement and diminishment of the intramolecular charge transfer (ICT) process, respectively. Kinetic studies revealed that DAPy and CBPy both exhibited highly efficient photo-activated oxidase-like activity with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate, which were in good accordance with their molecular engineering to promote either type I or type II reactive oxygen species (ROS) generation. Impressively a colorimetric method based on the visible light induced oxidase-like activity of molecular rotors was developed to determine the environmental temperature for the first time. Both DAPy and CBPy showed distinct sensitivities toward temperature as compared with several molecular rotors based on the typical fluorimetric detection. This work provides a new strategy for the application of molecular rotors to overcome the non-emissive challenge in temperature sensing., (© 2023 Wiley-VCH GmbH.)

Bioremediation of sediment organic pollution has been intensely investigated, but the degradation of complex organic compounds, pesticide residues, and polychlorinated biphenyls (PCBs) remains poorly studied. In this study, sediments were collected from Zhanjiang Mangrove Reserve and inoculated in an inorganic salt medium using only biphenyl (BP) and PCBs as the carbon sources to obtain a PCB-degrading strain. A gram-negative bacterium that metabolized PCBs was isolated and identified as Klebsiella Lw3 by 16S rDNA phylogenetic analysis. Genomic sequencing showed that this bacterium possessed genes related to BP/PCB degradation, and its GC content was 58.2%; we identified 3326 cellular pathways. Gas chromatography-mass spectrometry was employed to test the PCB degrading ability; the results showed that the strain had a good degradation effect on PCB3 at concentrations of 5, 10, 20, 40, and 60 mg/L and that the final degradation rate was higher than 97% after 96 h. Interestingly, this strain showed good biodegradability of PCBs despite having no classical PCB degradation pathway, providing a new direction for Klebsiella research with practical significance for in situ bioremediation of PCB contamination. Overall, this study provides valuable insights into the genetic structure of PCB-degrading strains as well as eco-friendly and low-cost PCB degradation and lays a foundation for the discovery of new degradation pathways.

Objective: To investigate the application of combined gastroscopy and laparoscopy (dual scope) in the treatment of early gastric cancer. Methods: In this descriptive case series study, we retrospectively collected data on 15 patients with cT1b stage gastric cancer who had undergone combined laparoscopic and endoscopic surgery in the 900th Hospital of the People's Liberation Army of China from May 2020 to October 2022. The study cohort comprised nine men and six women of median age 59 (range: 47-76) years and median body mass index 20.9 (range: 18.3-26.2) kg/m 2 . Seven of the lesions were located on the lesser curvature of the gastric antrum and eight in the gastric angle. All lesions were biopsied for pathological examination and evaluated by endoscopic ultrasonography, followed by endoscopic submucosal dissection (ESD) and laparoscopic regional lymph node dissection. Studied variables included surgical and pathological features, postoperative factors, and outcomes. Results: In this group of patients, the median (range) operative time for ESD was 45 (30-82) minutes, the duration of laparoscopic lymph node dissection (45.1±8.6) minutes, and the median (range) intraoperative blood loss during lymph node dissection 30 (10-80) mL. Of the 13 patients with negative postoperative horizontal margins, four were stage SM1 and had no lymph node metastases (Stage SM1) and nine were Stage SM2, of which had one positive regional lymph node and two received additional standard distal gastrectomy with D2 lymphadenectomy concurrently because of positive ESD specimens (lymph node negative). No lymph node metastases were found in the surgical specimens of these patients. The remaining two patients had positive vertical margins; both had undergone concurrent standard distal gastrectomy with D2 lymphadenectomy. One of them was found to be lymph node positive (No. 3, one node). Four patients had impaired gastric emptying after dual-scope treatment, all of whom recovered well with symptomatic management; one patient with a suspected lymphatic leak was also managed conservatively. There were no cases of postoperative bleeding, abdominal infection, or incisional infection. At a median follow-up of 14 (6-26) months, no tumor recurrence or metastasis had been identified in any of the patients. Three patients had a grade B nutrition score 3 to 6 months after surgery, all of whom had undergone major gastrectomy, and two patients who had undergone dual-scope surgery reported an increase in acid reflux and belching after surgery compared with the preoperative period. Conclusion: A combined technique is safe and feasible for the treatment of early gastric cancer and is worthy of further exploration.

Objectives: To investigate the association of single nucleotide polymorphisms (SNPs) of myeloid differentiation factor 88 ( MyD88 ) and Toll-like receptor adaptor molecule 1 ( TICAM1 ) and their interactions with community-acquired pneumonia (CAP) in children., Methods: Improved multiple ligase detection reaction assay was used for detecting the polymorphisms of nine tagging SNPs of the MyD88 and TICAM1 genes in 375 children with CAP who attended the Department of Pediatrics of the Second Affiliated Hospital of Yan'an University Medical School from August 2015 to September 2017 and 306 healthy children who underwent physical examination. A logistic regression analysis was used to evaluate the association between the distribution of genotypes and their interactions with CAP in children., Results: The polymorphism of the TICAM1 gene at rs11466711T/C locus was closely associated with the susceptibility to CAP in children ( P <0.05). The AA genotype of rs35747610G/A locus significantly reduced risk of sepsis in children with CAP ( P <0.05). The AA genotype of rs6510826G/A locus was significantly associated with the increase in C-reactive protein level in children with CAP ( P <0.05). The GG genotype of the MyD88 gene at rs7744A/G locus significantly increased the risk of respiratory failure and circulatory failure ( P <0.05). The multiplicative interactions between MyD88 gene rs7744A/G and TICAM1 gene rs11466711T/C, rs2292151G/A, rs35299700C/T, and rs35747610G/A loci were significantly associated with the susceptibility to CAP, the severity of CAP, and the risk of sepsis in children ( P <0.05)., Conclusions: The gene polymorphisms of MyD88 and TICAM1 and their interactions are closely associated with CAP in children, with a synergistic effect on the development and progression of CAP in children.

The linear constraint of secret key rate capacity is overcome by the twin-field quantum key distribution (QKD). However, the complex phase-locking and phase-tracking technique requirements throttle the real-life applications of the twin-field protocol. The asynchronous measurement-device-independent (AMDI) QKD, also called the mode-pairing QKD, protocol can relax the technical requirements and keep the similar performance of the twin-field protocol. Here, we propose an AMDI-QKD protocol with a nonclassical light source by changing the phase-randomized weak coherent state to a phase-randomized coherent-state superposition in the signal state time window. Simulation results show that our proposed hybrid source protocol significantly enhances the key rate of the AMDI-QKD protocol, while exhibiting robustness to imperfect modulation of nonclassical light sources.

Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy. However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ&#95;0002538 was markedly downregulated in patients with diabetic peripheral neuropathy. Further in vitro experiments showed that overexpression of circ&#95;0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ&#95;0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ&#95;0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ&#95;0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ&#95;0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy., Competing Interests: None

The central dogma of gene expression involves DNA transcription to RNA and RNA translation into protein. As key intermediaries and modifiers, RNAs undergo various forms of modifications such as methylation, pseudouridylation, deamination, and hydroxylation. These modifications, termed epitranscriptional regulations, lead to functional changes in RNAs. Recent studies have demonstrated crucial roles for RNA modifications in gene translation, DNA damage response, and cell fate regulation. Epitranscriptional modifications play an essential role in development, mechanosensing, atherogenesis, and regeneration in the cardiovascular (CV) system, and their elucidation is critically important to understanding the molecular mechanisms underlying CV physiology and pathophysiology. This review aims at providing biomedical engineers with an overview of the epitranscriptome landscape, related key concepts, recent findings in epitranscriptional regulations, and tools for epitranscriptome analysis. The potential applications of this important field in biomedical engineering research are discussed.

(1) Background: Hypertension is a complex, multifactorial disease that is caused by genetic and environmental factors. Apart from genetic predisposition, the mechanisms involved in this disease have yet to be fully understood. We previously reported that LEENE (lncRNA enhancing endothelial nitric oxide expression, transcribed from LINC00520 in the human genome) regulates endothelial cell (EC) function by promoting the expression of endothelial nitric oxide synthase (eNOS) and vascular growth factor receptor 2 (VEGFR2). Mice with genetic deletion of the LEENE/LINC00520 homologous region exhibited impaired angiogenesis and tissue regeneration in a diabetic hindlimb ischemia model. However, the role of LEENE in blood pressure regulation is unknown. (2) Methods: We subjected mice with genetic ablation of leene and wild-type littermates to Angiotensin II (AngII) and monitored their blood pressure and examined their hearts and kidneys. We used RNA-sequencing to identify potential leene -regulated molecular pathways in ECs that contributed to the observed phenotype. We further performed in vitro experiments with murine and human ECs and ex vivo experiments with murine aortic rings to validate the select mechanism. (3) Results: We identified an exacerbated hypertensive phenotype of leene -KO mice in the AngII model, evidenced by higher systolic and diastolic blood pressure. At the organ level, we observed aggravated hypertrophy and fibrosis in the heart and kidney. Moreover, the overexpression of human LEENE RNA, in part, restored the signaling pathways impaired by leene deletion in murine ECs. Additionally, Axitinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR suppresses LEENE in human ECs. (4) Conclusions: Our study suggests LEENE as a potential regulator in blood pressure control, possibly through its function in ECs., Competing Interests: J.W.R. received industry-sponsored research grant from Pfizer on an unrelated work. S.Z. is a founder and board member of Genemo Inc, San Diego, CA, USA.

Neural networks have achieved impressive breakthroughs in both industry and academia. How to effectively develop neural networks on quantum computing devices is a challenging open problem. Here, we propose a new quantum neural network model for quantum neural computing using (classically controlled) single-qubit operations and measurements on real-world quantum systems with naturally occurring environment-induced decoherence, which greatly reduces the difficulties of physical implementations. Our model circumvents the problem that the state-space size grows exponentially with the number of neurons, thereby greatly reducing memory requirements and allowing for fast optimization with traditional optimization algorithms. We benchmark our model for handwritten digit recognition and other nonlinear classification tasks. The results show that our model has an amazing nonlinear classification ability and robustness to noise. Furthermore, our model allows quantum computing to be applied in a wider context and inspires the earlier development of a quantum neural computer than standard quantum computers., (Copyright © 2023 Min-Gang Zhou et al.)

Background: IgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter., Case Presentation: An 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy., Conclusion: IgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients., (© 2023. The Author(s).)

As the nexus where rivers and oceans meet, estuaries are vulnerable to microplastic (MP) pollution derived from rivers. However, few studies have focused on the pollution status of MPs in small estuarine areas. Here, the abundance and characteristics of MPs in surface water and sediment samples from a small estuary, the Wanquan River estuary, were studied. The average abundance of MPs was 6573 ± 2659 n/m 3 in surface water and 1065 ± 696 n/kg dw in sediment samples from the Wanquan River estuary. Most of the MPs in water samples and sediments were red (92.9 % and 88.1 %) fragments (87.4 % and 95.5 %) with sizes <1.0 mm (90.8 % and 92.4 %) made up of antifouling paint particles (APPs) (83.5 % and 89.8 %), respectively. A significant positive correlation (p < 0.01) was found between the concentration of Cu 2+ and the abundance of APPs in sediment samples from the Wanquan River estuary. The APPs in the sediments can act as a continuous source of toxic chemicals (e.g., Cu 2+ ) to marine environments. The results of this study expand our knowledge about MP pollution in small estuaries, and the ecological risk of APPs in the Wanquan River estuary to aquatic organisms should not be ignored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)