Proton is Essential or Not: A Fresh Look on Pseudocapacitive Energy Storage of PANI Composites.

Protonation has been considered essential for the pseudocapacitive energy storage of polyaniline (PANI) for years, as proton doping in PANI chains not only activates electron transport pathways, but also promotes the proceeding of redox reactions. Rarely has the ability for PANI of storing energy without protonation been investigated, and it remains uncertain whether PANI has pseudocapacitive charge storage properties in an alkaline electrolyte. Here, this work first demonstrates the pseudocapacitive energy storage for PANI without protonation using a PANI/graphene composite as a model material in an alkaline electrolyte. Using in situ Raman spectroscopy coupled with electrochemical quartz crystal microbalance (EQCM) measurements, this work determines the formation of -N= group over potential on a PANI chain and demonstrates the direct contribution of OH- in the nonprotonation type of oxidation reactions. This work finds that the PANI/graphene composite in an alkaline electrolyte has excellent cycling stability with a wider operation voltage of 1 V as well as a slightly higher specific capacitance than that in an acidic electrolyte. The findings provide a new perspective on pseudocapacitive energy storage of PANI-based composites, which will influence the selection of electrolytes for PANI materials and expand their application in energy storage fields.

Computational design and engineering of self-assembling multivalent microproteins with therapeutic potential against SARS-CoV-2.

Multivalent drugs targeting homo-oligomeric viral surface proteins, such as the SARS-CoV-2 trimeric spike (S) protein, have the potential to elicit more potent and broad-spectrum therapeutic responses than monovalent drugs by synergistically engaging multiple binding sites on viral targets. However, rational design and engineering of nanoscale multivalent protein drugs are still lacking. Here, we developed a computational approach to engineer self-assembling trivalent microproteins that simultaneously bind to the three receptor binding domains (RBDs) of the S protein. This approach involves four steps: structure-guided linker design, molecular simulation evaluation of self-assembly, experimental validation of self-assembly state, and functional testing. Using this approach, we first designed trivalent constructs of the microprotein miniACE2 (MP) with different trimerization scaffolds and linkers, and found that one of the constructs (MP-5ff) showed high trimerization efficiency, good conformational homogeneity, and strong antiviral neutralizing activity. With its trimerization unit (5ff), we then engineered a trivalent nanobody (Tr67) that exhibited potent and broad neutralizing activity against the dominant Omicron variants, including XBB.1 and XBB.1.5. Cryo-EM complex structure confirmed that Tr67 stably binds to all three RBDs of the Omicron S protein in a synergistic form, locking them in the "3-RBD-up" conformation that could block human receptor (ACE2) binding and potentially facilitate immune clearance. Therefore, our approach provides an effective strategy for engineering potent protein drugs against SARS-CoV-2 and other deadly coronaviruses.

A Survey on the Current Status of Adult External Ventricular Drainage Care: Exploring Content Framework and the Need for Group Standards.

Background: External ventricular drainage (EVD), a widely used clinical procedure, faces slow translation of knowledge into practice due to practical barriers. The scarcity of high-quality data in the past EVD management and neurocritical care research compounds the challenge. Objective: This study aims to investigate the current status of adult external ventricular drainage care among neurosurgical nurses, delineate nursing priorities and challenges, and explore the necessity for establishing standardized guidelines for external ventricular drainage care. Methods: We conducted a systematic literature search to identify existing clinical guidelines, systematic reviews, evidence summaries, and expert consensus on adult external ventricular drainage care. We developed an electronic questionnaire titled "Survey on the Current Status of Adult External Ventricular Drainage Care" based on our search results. We distributed it to certified registered neurosurgical nurses working in the top 20 neurosurgery hospitals, per the 2022 Fudan Hospital Ranking published by the Institute of Hospital Management at Fudan University. Results: Effective control of drainage speed and total volume is a crucial aspect of nursing care. Existing guidelines primarily emphasize infection prevention in the context of complication care. However, it was observed that nursing staff exhibited limited knowledge concerning the total volume (58.7%) and rate of cerebrospinal fluid drainage (50.8%), as well as the management of complications (56.7%). Factors influencing the extent of nursing knowledge related to external ventricular drainage care include levels of education (P = .022), professional titles (P = .004), department assignments (P < .001), and the completion of relevant training (P = .01). Conclusions: Establishing standardized guidelines for external ventricular drainage care is imperative to bridge the gap between existing evidence and clinical practice.

ncRNA-mediated overexpression of ubiquitin-specific proteinase 13 contributes to the progression of prostate cancer via modulating AR signaling, DNA damage repair and immune infiltration.

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of prostate cancer, and the molecular mechanism driving mCRPC progression has not yet been fully elucidated. Immunotherapies such as chimeric antigen receptor, T-cell therapy and immune checkpoint blockade have exerted promising antitumor effects in hematological and solid tumor malignancies; however, no encouraging responses have been observed against mCRPC. The deubiquitinase USP13 functions as a tumor suppressor in many human cancers, as it sustains the protein stability of PTEN and TP53; however, its role in prostate cancer (PCa) and involvement in DNA damage and AR signaling remain unclear. In the current study, we explored the prognostic value of USP13 in PCa based on the TCGA database, and we analyzed the expression of USP13 in PCa tissues and adjacent normal tissues based on TCGA and our cohort. The results suggested that USP13 is overexpressed in PCa tumors and has the potential to be an independent biomarker for the overall survival of PCa patients. Additionally, enrichment analysis indicated that USP13 may participate in the AR pathway and PI3k/Wnt signaling, which are closely related to PCa progression. We also observed a significant correlation between the expression of USP13 and AR-related genes, DDR genes and mismatch repair genes based on the TCGA_PRAD dataset, which further supported the critical role of USP13 in AR activation and the DNA damage response of PCa. USP13 was also found to be enriched in protein neddylation, and expression of USP13 was significantly associated with infiltration of immune cells and expression of immunomodulators. Taken together, our study revealed a key role of USP13 in contributing to PCa progression by participating in multiple oncogenic signaling pathways, the DNA damage response and the immunosuppressive tumor microenvironment. Targeting USP13 may inhibit tumor growth and provide additional benefits in cooperation with DDR inhibitors and immunotherapy.

The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-ß superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. METHODS: The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin ßE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin ßE expression level and patient's clinicopathological indices was evaluated. RESULTS: In the normal renal tissue, inhibin ßE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin ßE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin ßE in the tumor tissue and tumor grade. Patients with a lower inhibin ßE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. CONCLUSIONS: INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

SNHG12 promotes carcinogenesis of human renal cell cancer via functioning as a competing endogenous RNA and sponging miR-30a-3p.

Small nucleolar RNA host gene 12 (SNHG12) has been indicated in the tumorigenesis of various human cancers, including clear cell renal cell carcinoma (ccRCC). However, the underlying mechanisms of SNHG12 driving progression of ccRCC remain incompletely understood. In the present study, we discovered that SNHG12 is up-regulated in ccRCC and that overexpression of SNHG12 predicted poor clinical outcome of ccRCC patients. SNHG12 knockdown notably inhibited proliferation and migration of RCC cells. Furthermore, we discovered that miR-30a-3p, a putative ccRCC inhibitor, was competitively sponged by SNHG12. Via the crosstalk network, SNHG12 was capable of up-regulating multiple target genes of miR-30a-3p, namely, RUNX2, WNT2 and IGF-1R, which have been identified to facilitate tumorigenesis of ccRCC. Taken together, our present study suggested a novel ceRNA network, in which SNHG12 could promote the malignancy of ccRCC although competitively binding with miR-30a-3p and consequently release the expression of its downstream cancer-related genes.

A theoretical study on the excited-state deactivation paths for the A-5FU dimer.

The photostability of DNA plays a key role in the normal function of organisms. A-5FU is a base pair derivative of the A-T dimer where the methyl group is replaced by a F atom. Here, accurate static TDDFT calculations and non-adiabatic dynamic simulations are used to systematically investigate the excited-state decay paths of the A-5FU dimer related to the proton transfer and the out-of-plane twisting deformation motion of A and 5FU in the 1ππ* and 1nπ* states. CC2 is used to check the accuracy of the current TDDFT calculations. Our results show that the deformation of the C[double bond, length as m-dash]C or C[double bond, length as m-dash]N double bond in A and 5FU provides an efficient pathway for the depopulation of the lowest excited states, which can compete with the excited-state proton transfer paths in the dimer. This finding indicates that monomer-like decay paths could be important for the photostability of weakly hydrogen-bonded DNA base pairs and provide a new insight into the excited-state decay paths in base pairs and their analogues.

Exploring microRNA target genes and identifying hub genes in bladder cancer based on bioinformatic analysis.

BACKGROUND: Bladder cancer (BC) is the second most frequent malignancy of the urinary system. The aim of this study was to identify key microRNAs (miRNAs) and hub genes associated with BC as well as analyse their targeted relationships. METHODS: According to the microRNA dataset GSE112264 and gene microarray dataset GSE52519, differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using the R limma software package. The FunRich software database was used to predict the miRNA-targeted genes. The overlapping common genes (OCGs) between miRNA-targeted genes and DEGs were screened to construct the PPI network. Then, gene ontology (GO) analysis was performed through the "cluster Profiler" and "org.Hs.eg.db" R packages. The differential expression analysis and hierarchical clustering of these hub genes were analysed through the GEPIA and UCSC Cancer Genomics Browser databases, respectively. KEGG pathway enrichment analyses of hub genes were performed through gene set enrichment analysis (GSEA). RESULTS: A total of 12 DEMs and 10 hub genes were identified. Differential expression analysis of the hub genes using the GEPIA database was consistent with the results for the UCSC Cancer Genomics Browser database. The results indicated that these hub genes were oncogenes, but VCL, TPM2, and TPM1 were tumour suppressor genes. The GSEA also showed that hub genes were most enriched in those pathways that were closely associated with tumour proliferation and apoptosis. CONCLUSIONS: In this study, we built a miRNA-mRNA regulatory targeted network, which explores an understanding of the pathogenesis of cancer development and provides key evidence for novel targeted treatments for BC.

No association between three polymorphisms (rs1800629, rs361525 and rs1799724) in the tumor necrosis factor-α gene and susceptibility to prostate cancer: a comprehensive meta-analysis.

BACKGROUND: Inflammation is one of the factors associated with prostate cancer. The cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in inflammation. Several studies have focused on the association between TNF-α polymorphisms and prostate cancer development. Our meta-analysis aimed to estimate the association between TNF-α rs1800629 (- 308 G/A), rs361525 (- 238 G/A) and rs1799724 polymorphisms and prostate cancer risk. METHODS: Eligible studies were identified from electronic databases (PubMed, Embase, Wanfang and CNKI) using keywords: TNF-α, polymorphism, prostate cancer, until Nov 15, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the association from a quantitative point-of-view. Publication bias and sensitivity analysis were also applied to evaluate the power of current study. All statistical analyses were done with Stata 11.0 software. RESULTS: Twenty-two different articles were included (22 studies about rs1800629; 8 studies for rs361525 and 5 studies related to rs1799724). Overall, no significant association was found between rs1800629 and rs1799724 polymorphisms and the risk of prostate cancer in the whole (such as: OR = 1.03, 95% CI = 0.92-1.16, P = 0.580 in the allele for rs1800629; OR = 0.95, 95% CI = 0.84-1.07, P = 0.381 in the allele for rs1799724). The rs361525 polymorphism also had no association with prostate cancer in the cases (OR = 0.93, 95% CI = 0.66-1.32, P = 0.684 in the allele) and ethnicity subgroup. The stratified subgroup of genotype method, however, revealed that the rs361525 variant significantly decreased the risk of prostate cancer in the Others (OR = 0.65, 95% CI = 0.47-0.89, P = 0.008, A-allele vs G-allele) and PCR-RFLP (OR = 2.68, 95% CI = 1.00-7.20, P = 0.050, AG vs GG or AA+AG vs GG) methods. CONCLUSIONS: In summary, the findings of the current meta-analysis indicate that the TNF-α rs1800629, rs361525 and rs1799724 polymorphisms are not correlated with prostate cancer development, although there were some pooled positive results. Further well-designed studies are necessary to form more precise conclusions.

Superantigen staphylococcal enterotoxin C1 inhibits the growth of bladder cancer.

Superantigens can induce cell-mediated cytotoxicity preferentially against MHC II-positive target cells with large amounts of inflammatory cytokines releasing. In this study, superantigen staphylococcal enterotoxin C (SEC) 1 was investigated to evaluate its potential in bladder cancer immunotherapy in vitro and in vivo. Our results revealed that SEC1 could stimulate the proliferation of human peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, accompanied with the release of interleukin-2, interferon-γ, and tumor necrosis factor-α, and increased the population of CD4+ T cells and CD8+ T cells. PBMCs stimulated by SEC1 could initiate significant cytotoxicity towards human bladder cancer cells in vitro. The results of in vivo antitumor experiment indicated that SEC1 could decrease the rate of tumor formation and prolong the survival time of tumor-bearing mice. Our study demonstrated that SEC1 inhibited the growth of bladder cancer. And it is also suggested that SEC1 may become a candidate for bladder cancer immunotherapy.

Significant association among the Fas -670 A/G (rs1800682) polymorphism and esophageal cancer, hepatocellular carcinoma, and prostate cancer susceptibility: a meta-analysis.

The Fas gene plays a key role in regulation of apoptotic cell death, and corruption of this signaling pathway has been shown to participate in immune escape and tumorgenesis. Single-nucleotide polymorphism in the promoter of Fas gene at position -670 A/G may affect its expression and play an important role in the pathology of many kinds of cancer. The association between Fas -670 A/G polymorphism and cancer risk is still controversial and ambiguous. Therefore, we conducted a meta-analysis of the currently literature to clarify this relationship. We conducted a search in the PubMed, EMbase, CNKI, and WanFang databases, covering all papers published by May 5, 2014. Overall, 59 case-control studies with 17,035 cases and 23,155 controls were retrieved based on the search criteria for cancer susceptibility related to -670 A/G polymorphism in Fas gene. Odds ratios (OR) and 95% confidence intervals (CI) revealed association strengths. Although no significant relationship was detected between Fas -670 A/G polymorphism and whole cancer risk, in the ethnicity subgroup, significant associations were found in three types of cancer: prostate cancer (OR = 1.06, 95% CI = 1.01-1.11 for A-allele vs. G-allele); hepatocellular carcinoma (OR = 0.89, 95% CI = 0.80-0.99 for AG vs. GG); esophageal cancer (OR = 0.95, 95% CI = 0.92-0.99 for AA + AG vs. GG). Moreover, lower cancer risk was found in smokers carried A-allele, when compared to smokers carried the GG genotype. The Fas -670 A/G polymorphism may be associated with esophageal cancer, hepatocellular carcinoma, and prostate cancer susceptibility from our meta-analysis. Studies with larger samples and gene-environment interactions are warranted to understand the role of Fas -670 A/G polymorphism for cancer risk.

Analysis of combined detection of N-terminal pro-B-type natriuretic peptide and left ventricular ejection fraction in heart function in patients with acute CO poisoning.

OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used in the evaluation on heart function in many heart diseases. However, little is known in patients with acute carbon monoxide poisoning (ACOP). Left ventricular ejection fraction (LVEF) can be applied as a preliminary test method to measure the left ventricular function. In the present study, we investigate the clinical significance of NT-proBNP combined with LVEF on heart function in 68 patients with ACOP. METHODS: A total of 68 ACOP patients hospitalized were divided into 3 groups: the mild, the moderate, and the severe group. During the same period, 30 healthy volunteers were chosen to represent the control group. The serum NT-proBNP was immediately measured and LVEF was monitored by an echocardiogram within 24 hours after admission. All data were analyzed and compared for the groups investigated. RESULTS: N-terminal pro-B-type natriuretic peptide showed a significant increase and LVEF a considerable decrease in all 3 clinic groups (P < .01) when compared with the control group. Levels of NT-proBNP are increased and levels of LVEF are decreased when the clinic group changed from mild, moderate, to severe. N-terminal pro-B-type natriuretic peptide is negatively correlated with LVEF (r = -0.955, P = .045). Combined detection of NT-proBNP and LVEF in the diagnosis of heart function was found to be more sensitive compared with the single index after ACOP (χ(2) = 14.636, P < .05). CONCLUSION: There are an increased level of NT-proBNP and a decrease of LVEF, which represents a clear sign of heart malfunction by ACOP. Combined NT-proBNP and LVEF detection technique has a significant advantage in the diagnosis of patients with myocardial contraction function damage after ACOP.

[Impact of insertion timing of iodophor cotton ball on the control of infection complications after transrectal ultrasound guided prostate biopsy].

OBJECTIVE: To explore the impact of insertion timing of iodophor cotton ball on the control of infection complications after transrectal ultrasound (TRUS) guided prostate biopsy. METHODS: A total of 197 patients undergoing TRUS-guided prostate biopsy from March 2012 to January 2013 were randomly divided into post-discharge, pre-discharge and pre-discharge plus post-discharge groups. A prospective study was made on the symptoms of infections, signs and relevant laboratory examinations in all three groups. RESULTS: Infections occurred in 6/66 patients in the post-discharge group and 2 patients in the other two groups. The prevalence rates were 7.58%, 3.08% and 3.03% respectively. Statistically significant difference existed in the prevalence rate between pre-discharge and post-discharge groups (P < 0.05). Yet no statistically significant difference existed between pre-discharge and pre-discharge plus post-discharge groups (P > 0.05). CONCLUSION: During the TRUS guided prostate biopsy, inserting an iodophor cotton ball before placing an ultrasonic probe to the rectum can control the infection and reduce its prevalence rate.

[Value of magnetic resonance imaging for early diagnosis of prostatic carcinoma in central zone].

OBJECTIVE: To explore the magnetic resonance imaging (MRI) manifestations of early prostatic carcinoma (PCa) in central zone (CZ) . METHODS: A total of 284 cases of PCa were scanned by MRI while 24 cases of carcinoma in 28 PCa focus were in central zone. Their T1WI, T2WI, DWI and ADC value characteristics were analyzed respectively and the completeness of annular low signal between central and peripheral zones were observed. At the same time, 45 cases of PCa were located in peripheral zone (PZ) . Twenty cases of benign prostatic hyperplasia (BPH) were comparatively analyzed. All cases received a histological diagnosis. RESULTS: Most cases of early PCa in CZ demonstrated ill-defined margin, amorphous shape and equal signal intensity on T1WI, low signal intensity on T2WI and high signal intensity on DWI. The mean ADC value for PCa focus was (0.867 ± 0.074)×10(-3) mm(2)/s and PCa foci were enhanced slightly. In these cases, most annular low signals between CZ and PZ were destroyed. The difference of ADC values between PCa in CZ and PZ groups ((0.914 ± 0.066) ×10(-3) mm(2)/s ) had no statistic significance (P > 0.05) , but the ADC values between PCa and BPH in CZ groups ((1.517 ± 0.315) ×10(-3) mm(2)/s ) had statistically significant difference (P < 0.05). CONCLUSION: Some reliable diagnostic characteristics on MRI may be used for an early diagnosis of PCa in CZ.

Senolytic combination of dasatinib and quercetin attenuates renal damage in diabetic kidney disease.

BACKGROUND: Senolytic combination of dasatinib and quercetin (DQ) is the most studied senolytics drugs used to treat various age-related diseases. However, its protective activity against diabetic kidney disease (DKD) and underlying mechanisms are uncertain. PURPOSE: To investigate the functions and potential mechanisms of the senolytics DQ on DKD. METHODS: Diabetic db/db mice were administrated DQ or transfected with over-expressed PPARα or shPPARα vector. The positive control group was administered irbesartan. Renal function and fibrotic changes in kidney tissue were tested. Single-cell RNA-seq (scRNA-seq) was conducted to analyze the differential transcriptome between the diabetic and control mice. Molecular docking simulation was used to assess the combination of DQ and potential factors. Moreover, tubular epithelial cells under high-glucose (HG) conditions were incubated with DQ and transfected with or without over-expressed PPARα/siPPARα vector. RESULTS: DQ significantly improved renal function, histopathological and fibrotic changes, alleviated lipid deposition, and increased ATP levels in mice with DKD. DQ reduced multiple fatty acid oxidation (FAO) pathway-related proteins and up-regulated PPARα in db/db mice. Overexpression of PPARα upregulated the expression of PPARα-targeting downstream FAO pathway-related proteins, restored renal function, and inhibited renal fibrosis in vitro and in vivo. Moreover, molecular docking and dynamics simulation analyses indicated the nephroprotective effect of DQ via binding to PPARα. Knockdown of PPARα reversed the effect of DQ on the FAO pathway and impaired the protective effect of DQ during DKD. CONCLUSION: For the first time, DQ was found to exert a renal protective effect by binding to PPARα and attenuating renal damage through the promotion of FAO in DKD.

Immobile polyanionic backbone enables a 900-µm-thick electrode for compact energy storage with unprecedented areal capacitance.

Thickening of electrodes is crucial for maximizing the proportion of active components and thus improving the energy density of practical energy storage cells. Nevertheless, trade-offs between electrode thickness and electrochemical performance persist because of the considerably increased ion transport resistance of thick electrodes. Herein, we propose accelerating ion transport through thick and dense electrodes by establishing an immobile polyanionic backbone within the electrode pores; and as a proof of concept, gel polyacrylic electrolytes as such a backbone are in situ synthesized for supercapacitors. During charge and discharge, protons rapidly hop among RCOO- sites for oriented transport, fundamentally reducing the effects of electrode tortuosity and polarization resulting from concentration gradients. Consequently, nearly constant ion transport resistance per unit thickness is achieved, even in the case of a 900-µm-thick dense electrode, leading to unprecedented areal capacitances of 14.85 F cm-2 at 1 mA cm-2 and 4.26 F cm-2 at 100 mA cm-2. This study provides an efficient method for accelerating ion transport through thick and dense electrodes, indicating a significant solution for achieving high energy density in energy storage devices, including but not limited to supercapacitors.

Genotype and clinical phenotype characteristics of MAX germline mutation-associated pheochromocytoma/paraganglioma syndrome.

Objective: The aim of this study was to investigate the genotypic and clinical phenotypic characteristics of MAX germline mutation-associated pheochromocytoma (PCC) and paraganglioma (PGL). Methods: We retrospectively analyzed the family investigation data and clinical genetic characteristics of six individuals from three independent families with PCC carrying MAX germline mutations from December 2005 to March 2024. A literature review was then conducted of the six carriers and another 103 carriers from the other 84 families with MAX germline mutations reported previously. Results: There were 109 patients in 87 families with all five exons and 53 types of MAX germline mutations. p.R33* (c.97C>T; 21.1%), p.R75* (c.223C>T; 13.8%), and p.A67D (c.200C>A; 7.3%), which accounted for 42.2% of mutations detected, were the most common mutations. Moreover, 101 (92.7%) patients developed PCCs, including 59 bilateral PCCs and 42 unilateral PCCs, and 19 (18.8%) patients showed metastasis. The mean age at diagnosis was 32.8 ± 12.6 (13-80) years. The male-to-female ratio was 1.3:1. In 11 (10.9%) patients, the PCC was accompanied by chest or abdominal PGL, and one other patient had sole head and neck PGL. Nine (8.3%) patients also had functional pituitary adenomas, 11 (10.9%) developed other neuroendocrine tumors (NETs), and 7 (6.4%) presented with concomitant non-NET. Meanwhile, MAX-p.Q82Tfs*89 and p.E158A mutations are reported for the first time in this study. Conclusion: MAX germline mutations may cause new types of multiple endocrine neoplasia. A comprehensive baseline assessment of neural crest cell-derived diseases is recommended for all individuals with MAX germline mutations. The risk of bilateral and metastatic PCCs should also be considered.

Ultrastructure of lymphatic stomata in the tunica vaginalis of humans.

Lymphatic stomata are small openings of lymphatic capillaries on the surface of the mesothelium that lines the serous cavity and have the function of active absorption. They play an important role in physiological and pathological conditions. The cavity of the tunica vaginalis is a typical serous cavity of the testis, but the lymphatic stomata of the tunica vaginalis of humans have never been reported. Here, we studied their ultrastructure by scanning and transmission electron microscopy. The submesothelial connective tissue with foramina was investigated after the mesothelial cells were digested using NaOH solution. We found the lymphatic stomata in cuboidal mesothelial cell regions of the parietal layer of the tunica vaginalis of humans with a diameter of about 1-2 µm. Sometimes, closed lymphatic stomata could be observed. Our study is the first to report the existence of lymphatic stomata of the tunica vaginalis of humans. We found that the tunica vaginalis cavity is connected with the lymphatic system through the stomata, which might provide a morphological basis for the drainage of hydrocele and tumor metastasis of the tunica vaginalis of humans.

[Subsequent retroperitoneoscopy for patients with previous ipsilateral retroperitoneal surgery].

OBJECTIVE: To evaluate the feasibility and clinical results of subsequent retroperitoneoscopic surgery for patients with previous ipsilateral retroperitoneal surgery through frank incision. METHODS: A total of 10 patents were selected for subsequent laparoscopic surgery through retroperitoneal approach. Among them, there were recurrent renal cysts (n = 4) including a history of open surgery (n = 1) and retroperitoneal surgery (n = 3) and nonfunctional kidneys (n = 6) including open nephropyelopolasty (n = 3), retroperitoneoscopic nephropyelopolasty (n = 1) and retroperitoneoscopic ureterolithotomy (n = 2). The mean surgical duration was (12-85) 38.6 months. All patients underwent retroperitoneoscopy. Decortication was performed for renal cysts and nephrectomy for nonfunctional kidneys. RESULTS: All operations were successfully performed with a mean surgical duration of 97 (40-185) minutes and a mean volume of blood loss 125 (20-460) ml. Among 4 cases with intraoperative peritoneal rupture, one case had renal cyst on ventral side. After enlargement, the procedure was performed through peritoneal cavity. The mean postoperative hospital stay was 5.6 (3-9) days. Nine patients received a mean follow-up period of 21.5 (3-47) months. All symptoms were relieved without any occurrence of postoperative complications. CONCLUSION: For patients with previous ipsilateral retroperitoneal surgery, retroperitoneoscopy may be feasible for properly selected cases.

Cyclic Differentiable Architecture Search.

Differentiable ARchiTecture Search, i.e., DARTS, has drawn great attention in neural architecture search. It tries to find the optimal architecture in a shallow search network and then measures its performance in a deep evaluation network. The independent optimization of the search and evaluation networks, however, leaves a room for potential improvement by allowing interaction between the two networks. To address the problematic optimization issue, we propose new joint optimization objectives and a novel Cyclic Differentiable ARchiTecture Search framework, dubbed CDARTS. Considering the structure difference, CDARTS builds a cyclic feedback mechanism between the search and evaluation networks with introspective distillation. First, the search network generates an initial architecture for evaluation, and the weights of the evaluation network are optimized. Second, the architecture weights in the search network are further optimized by the label supervision in classification, as well as the regularization from the evaluation network through feature distillation. Repeating the above cycle results in a joint optimization of the search and evaluation networks and thus enables the evolution of the architecture to fit the final evaluation network. The experiments and analysis on CIFAR, ImageNet and NATS-Bench [95] demonstrate the effectiveness of the proposed approach over the state-of-the-art ones. Specifically, in the DARTS search space, we achieve 97.52% top-1 accuracy on CIFAR10 and 76.3% top-1 accuracy on ImageNet. In the chain-structured search space, we achieve 78.2% top-1 accuracy on ImageNet, which is 1.1% higher than EfficientNet-B0. Our code and models are publicly available at https://github.com/microsoft/Cream.