A novel splice-altering TNC variant (c.5247A > T, p.Gly1749Gly) in an Chinese family with autosomal dominant non-syndromic hearing loss.

BACKGROUND: This study aims to analyze the pathogenic gene in a Chinese family with non-syndromic hearing loss and identify a novel mutation site in the TNC gene. METHODS: A five-generation Chinese family from Anhui Province, presenting with autosomal dominant non-syndromic hearing loss, was recruited for this study. By analyzing the family history, conducting clinical examinations, and performing genetic analysis, we have thoroughly investigated potential pathogenic factors in this family. The peripheral blood samples were obtained from 20 family members, and the pathogenic genes were identified through whole exome sequencing. Subsequently, the mutation of gene locus was confirmed using Sanger sequencing. The conservation of TNC mutation sites was assessed using Clustal Omega software. We utilized functional prediction software including dbscSNV_AdaBoost, dbscSNV_RandomForest, NNSplice, NetGene2, and Mutation Taster to accurately predict the pathogenicity of these mutations. Furthermore, exon deletions were validated through RT-PCR analysis. RESULTS: The family exhibited autosomal dominant, progressive, post-lingual, non-syndromic hearing loss. A novel synonymous variant (c.5247A > T, p.Gly1749Gly) in TNC was identified in affected members. This variant is situated at the exon-intron junction boundary towards the end of exon 18. Notably, glycine residue at position 1749 is highly conserved across various species. Bioinformatics analysis indicates that this synonymous mutation leads to the disruption of the 5' end donor splicing site in the 18th intron of the TNC gene. Meanwhile, verification experiments have demonstrated that this synonymous mutation disrupts the splicing process of exon 18, leading to complete exon 18 skipping and direct splicing between exons 17 and 19. CONCLUSION: This novel splice-altering variant (c.5247A > T, p.Gly1749Gly) in exon 18 of the TNC gene disrupts normal gene splicing and causes hearing loss among HBD families.

Placenta-derived mesenchymal stem cells promote diabetic wound healing via exosomal protein interaction networks.

There is a lack of effective treatment options for diabetic refractory wounds, which presents a critical clinical issue that needs to be addressed urgently. Our research has demonstrated that human placenta-derived mesenchymal stem cells (plaMSCs) facilitate the migration and proliferation of HaCat cells, thereby enhancing diabetic wound healing primarily via the exosomes derived from plaMSCs (plaMSCs-Ex). Using label-free proteomics, plaMSCs and their exosomes were analysed for proteome taxonomic content in order to explore the underlying effective components mechanism of plaMSCs-Ex in diabetic wound healing. Differentially expressed proteins enriched in plaMSCs-Ex were identified and underwent bioinformatics analysis including GO annotation, KEGG pathway enrichment, gene set enrichment analysis (GSEA) and protein-protein interaction analysis (PPI). Results showed that the proteins enriched in plaMSCs-Ex are significantly involved in extracellular matrix organisation, epithelium morphogenesis, cell growth, adhesion, proliferation and angiogenesis. PPI analysis filtered 2 wound healing-related clusters characterised by hub proteins such as POSTN, FN1, SPARC, TIMP1, SERPINE1, LRP1 and multiple collagens. In brief, the exosomal proteins derived from plaMSCs reveal diverse functions of regeneration and tissue remodelling based on proteomics analysis and potentially play a role in diabetic wound healing.

Comparison of aqueous and non-aqueous capillary electrophoresis for the determination of four benzalkonium chloride homologues in compound chemical disinfectants.

A new method was established for the simultaneous analysis of four homologous benzalkonium chlorides (dodecyldimethylbenzyl ammonium chloride, tetradecyldimethylbenzyl ammonium chloride, hexadecyldimethylbenzyl ammonium chloride, and octadecyldimethylbenzyl ammonium chloride) in compound chemical disinfectants using non-aqueous capillary electrophoresis (CE) based on a micellar electrokinetic chromatography mode with direct ultraviolet detection. The separation was performed on an uncoated fused quartz capillary with a total length of 60.2 cm and a diameter of 25 µm. The separation buffer consisted of a mixture of methanol/acetonitrile (60:40, v/v) containing 70 mmol/L sodium acetate, 60 mmol/L trifluoroacetic acid and 20 mmol/L sodium dodecyl sulfate. The sample buffer was a methanol solution containing only 2 mmol/L trifluoroacetic acid. The separation voltage was set at 8 kV with a working current of approximately 2.3 µA. The detection wavelength was 214 nm. Under optimal conditions, the limit of detection and limit of quantification for these four benzalkonium chlorides (BACs) were 1.0 mg/L and 5.0 mg/L, respectively. Good linearities were observed in the concentration ranges from 5.0 to 100.0 mg/L, with correlation coefficients above 0.999 for all compounds. The recoveries of these four BACs ranged from 92.5 % to 109.1 % with relative standard deviations below 4.7 %. With the new method, all four BACs could be analyzed in a single injection. In contrast, the aqueous CE method in the National Standard GB/T 26369-2020 only allowed for the simultaneous analysis of the first three homologous. The new method demonstrated the improved peak shape compared to the aqueous CE method and then was successfully applied to the analysis of 19 commercially available samples, such as object table disinfectants, hand sanitizers, and disinfectant wipes, which claimed to contain quaternary ammonium compound. The results obtained using the new method were compared with those of the aqueous CE of the National Standard Method, and no statistically significant differences were observed. The new method is simple in pre-treatment and provides accurate results, making it highly suitable for routine analysis.

Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen.

INTRODUCTION: Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC-A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. METHODS: Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC-A measurements in 2014-2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC-A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. RESULTS: Eighty patients were included. LCGM models identified two distinct trajectories of SCC-A: low-stable (40%; n = 32) and high-decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23-10.53], p = 0.019), progression-free survival (HR [95% CI]: 11.33 [3.19-40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high-decline arm. CONCLUSION: PC patients' SCC-A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC-A might assist tumor monitoring after systemic therapies.

Quantitative trait loci mapping provides insights into the genetic regulation of dendritic cell numbers in mouse tissues.

To explore the influence of genetics on homeostatic regulation of dendritic cell (DC) numbers, we present a screen of DCs and their progenitors in lymphoid and non-lymphoid tissues in Collaborative Cross (CC) and Diversity Outbred (DO) mice. We report 30 and 71 loci with logarithm of the odds (LOD) scores >8.18 and ranging from 6.67 to 8.19, respectively. The analysis reveals the highly polygenic and pleiotropic architecture of this complex trait, including many of the previously identified genetic regulators of DC development and maturation. Two SNPs in genes potentially underlying variation in DC homeostasis, a splice variant in Gramd4 (rs235532740) and a missense variant in Orai3 (rs216659754), are confirmed by gene editing using CRISPR-Cas9. Gramd4 is a central regulator of DC homeostasis that impacts the entire DC lineage, and Orai3 regulates cDC2 numbers in tissues. Overall, the data reveal a large number of candidate genes regulating DC homeostasis in vivo.

Surface Molecular Engineering for Fully Textured Perovskite/Silicon Tandem Solar Cells.

Developing large-scale monolithic perovskite/silicon tandem devices based on industrial Czochralski silicon wafers will likely have to adopt double-side textured architecture, given their optical benefits and low manufacturing costs. However, the surface engineering strategies that are widely used in solution-processed perovskites to regulate the interface properties are not directly applicable to micrometric textures. Here, we devise a surface passivation strategy by dynamic spray coating (DSC) fluorinated thiophenethylammonium ligands, combining the advantages of providing conformal coverage and suppressing phase conversion on textured surfaces. From the viewpoint of molecular engineering, theoretical calculation and experimental results demonstrate that introducing trifluoromethyl group provide more effective surface passivation through strong interaction and energy alignment by forming a dipole layer. Consequently, the DSC treatment of this bifunctional molecule enables the tandem cells based on industrial silicon wafers to achieve a certified stabilized power conversion efficiency of 30.89%. In addition, encapsulated devices display excellent operational stability by retaining over 97% of their initial performance after 600 h continuous illumination.

The association between plasma trans-fatty acids level and migraine: A cross-sectional study from NHANES 1999-2000.

OBJECTIVES: Trans-fatty acid (TFA) has been linked to an increased risk of a variety of diseases, such as cardiovascular disease (CVD), diabetes, and cancer. However, the relationship between plasma TFAs and migraine is little known. The current study aimed to determine the association between plasma TFAs and migraine in a large cross-sectional study among U.S. adults. METHODS: The participants from the US National Health and Nutrition Examination Survey (NHANES) were included during the period 1999-2000. The plasma concentrations of four major TFAs, including palmitelaidic acid (C16:1n-7t), elaidic acid (C18:1n-9t), vaccenic acid (C18:1n-7t), and linolelaidic acid (C18:2n-6t, 9t) were measured by gas chromatography/mass spectrometry (GC/MS). The presence of migraine headache was determined by self-report questionnaire. Weighted multivariable logistic regressions and restricted cubic spline (RCS) regressions were explored to assess the relationship between plasma TFAs and migraine. Furthermore, stratified analysis and testing of interaction terms were used to evaluate the effect modification by sex, age, race/ethnicity, family income, and BMI. RESULTS: A total of 1534 participants were included. The overall weighted prevalence of severe headache or migraine was 21.2 %. After adjusting for all potential covariates, plasma levels of elaidic acid and linolelaidic acid were positively associated with migraine. The adjusted OR values were 1.18 (95 %CI: 1.08-1.29, p=0.014, per 10 units increase) and 1.24 (95 %CI: 1.07-1.44, p=0.024). Then the included participants were divided into 2-quantiles by plasma TFA levels. Compared with participants with lower plasma levels of elaidic acid and linolelaidic acid (Q1 groups), those in the Q2 group had a higher prevalence of migraine when adjusted for all covariates in Model 2. The adjusted OR values were 2.43 (95 %CI: 1.14-5.18, p=0.037) for elaidic acid, and 2.18 (95 %CI: 1.14-4.20, p=0.036) for linolelaidic acid. Results were robust when analyses were stratified by sex, age, race/ethnicity, family income, and BMI, and no effect modification on the association was found. CONCLUSIONS: Our results demonstrated a positive association between migraine prevalence and plasma levels of elaidic acid and linolelaidic acid in US adults. These results highlight the connection between circulating TFAs and migraine.

Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB.

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.

YAP in development and disease: Navigating the regulatory landscape from retina to brain.

The distinctive role of Yes-associated protein (YAP) in the nervous system has attracted widespread attention. This comprehensive review strategically uses the retina as a vantage point, embarking on an extensive exploration of YAP's multifaceted impact from the retina to the brain in development and pathology. Initially, we explore the crucial roles of YAP in embryonic and cerebral development. Our focus then shifts to retinal development, examining in detail YAP's regulatory influence on the development of retinal pigment epithelium (RPE) and retinal progenitor cells (RPCs), and its significant effects on the hierarchical structure and functionality of the retina. We also investigate the essential contributions of YAP in maintaining retinal homeostasis, highlighting its precise regulation of retinal cell proliferation and survival. In terms of retinal-related diseases, we explore the epigenetic connections and pathophysiological regulation of YAP in diabetic retinopathy (DR), glaucoma, and proliferative vitreoretinopathy (PVR). Lastly, we broaden our exploration from the retina to the brain, emphasizing the research paradigm of "retina: a window to the brain." Special focus is given to the emerging studies on YAP in brain disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), underlining its potential therapeutic value in neurodegenerative disorders and neuroinflammation.

Associations between Geriatric Nutrition Risk Index, bone mineral density and body composition in type 2 diabetes patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM), a fast-growing issue in public health, is one of the most common chronic metabolic disorders in older individuals. Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities. In people with T2DM, the association between nutrition, sarcopenia, and osteoporosis has rarely been explored. AIM: To evaluate the connections among nutrition, bone mineral density (BMD) and body composition in patients with T2DM. METHODS: We enrolled 689 patients with T2DM for this cross-sectional study. All patients underwent dual energy X-ray absorptiometry (DXA) examination and were categorized according to baseline Geriatric Nutritional Risk Index (GNRI) values calculated from serum albumin levels and body weight. The GNRI was used to evaluate nutritional status, and DXA was used to investigate BMD and body composition. Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index. RESULTS: Of the total patients, 394 were men and 295 were women. Compared with patients in tertile 1, those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c, higher BMD at all bone sites, and higher appendicular skeletal muscle index (ASMI). These important trends persisted even when the patients were divided into younger and older subgroups. The GNRI was positively related to ASMI (men: r = 0.644, P < 0.001; women: r = 0.649, P < 0.001), total body fat (men: r = 0.453, P < 0.001; women: r = 0.557, P < 0.001), BMD at all bone sites, lumbar spine (L1-L4) BMD (men: r = 0.110, P = 0.029; women: r = 0.256, P < 0.001), FN-BMD (men: r = 0.293, P < 0.001; women: r = 0.273, P < 0.001), and hip BMD (men: r = 0.358, P < 0.001; women: r = 0.377, P < 0.001). After adjustment for other clinical parameters, the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck. Additionally, a low lean mass index and higher ß-collagen special sequence were associated with low BMD at all bone sites. Age was negatively correlated with ASMI, whereas weight was positively correlated with ASMI. CONCLUSION: Poor nutrition, as indicated by a low GNRI, was associated with low levels of ASMI and BMD at all bone sites in T2DM patients. Using the GNRI to evaluate nutritional status and using DXA to investigate body composition in patients with T2DM is of value in assessing bone health and physical performance.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Airborne antibiotic resistome and microbiome in pharmaceutical factories.

Antimicrobial resistance is considered to be one of the biggest public health problems, and airborne transmission is an important but under-appreciated pathway for the spread of antibiotic resistance genes (ARGs) in the environment. Previous research has shown pharmaceutical factories to be a major source of ARGs and antibiotic resistant bacteria (ARB) in the surrounding receiving water and soil environments. Pharmaceutical factories are hotspots of antibiotic resistance, but the atmospheric transmission and its environmental risk remain more concerns. Here, we conducted a metagenomic investigation into the airborne microbiome and resistome in three pharmaceutical factories in China. Soil (average: 38.45%) and wastewater (average: 28.53%) were major contributors of airborne resistome. ARGs (vanR/vanS, blaOXA, and CfxA) conferring resistance to critically important clinically used antibiotics were identified in the air samples. The wastewater treatment area had significantly higher relative abundances of ARGs (average: 0.64 copies/16S rRNA). Approximately 28.2% of the detected airborne ARGs were found to be associated with plasmids, and this increased to about 50% in the wastewater treatment area. We have compiled a list of high-risk airborne ARGs found in pharmaceutical factories. Moreover, A total of 1,043 viral operational taxonomic units were identified and linked to 47 family-group taxa. Different CRISPR-Cas immune systems have been identified in bacterial hosts in response to phage infection. Similarly, higher phage abundance (average: 2451.70 PPM) was found in the air of the wastewater treatment area. Our data provide insights into the antibiotic resistance gene profiles and microbiome (bacterial and non-bacterial) in pharmaceutical factories and reveal the potential role of horizontal transfer in the spread of airborne ARGs, with implications for human and animal health.

Surface Engineering of Perovskite Single Crystals by Atomic Layer Deposited Tin Oxide for Optical Communication.

Perovskite single crystals with excellent physical properties have broad prospects in the field of optoelectronics. However, the presence of dangling bonds, surface dislocations, and chemical impurities results in high surface defect density and sensitivity to humidity. Unfortunately, there are relatively few surface engineering strategies for single perovskite single crystals. We present a strategy utilizing atomic layer deposited SnOx to passivate surface defects in perovskite single crystals. The photodetector prepared based on the modified FAPbBr3 single crystals exhibits a low dark current of 1.89 × 10-9 A at a 5 V bias, close to 4 times lower with respect to the pristine device, a high detectivity of 2.3 × 1010 jones, and a fast response time of 27 µs. Moreover, the photodetectors feature long-term operational stability because the presence of a dense SnOx capping layer hinders the ingress of moisture and diffusion of ions. We further demonstrate the promise of our perovskite single crystal detectors for real-time subaqueous optical communication.

Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Breaking genetic shackles: The advance of base editing in genetic disorder treatment.

The rapid evolution of gene editing technology has markedly improved the outlook for treating genetic diseases. Base editing, recognized as an exceptionally precise genetic modification tool, is emerging as a focus in the realm of genetic disease therapy. We provide a comprehensive overview of the fundamental principles and delivery methods of cytosine base editors (CBE), adenine base editors (ABE), and RNA base editors, with a particular focus on their applications and recent research advances in the treatment of genetic diseases. We have also explored the potential challenges faced by base editing technology in treatment, including aspects such as targeting specificity, safety, and efficacy, and have enumerated a series of possible solutions to propel the clinical translation of base editing technology. In conclusion, this article not only underscores the present state of base editing technology but also envisions its tremendous potential in the future, providing a novel perspective on the treatment of genetic diseases. It underscores the vast potential of base editing technology in the realm of genetic medicine, providing support for the progression of gene medicine and the development of innovative approaches to genetic disease therapy.

Serotype distribution and antimicrobial resistance of pediatric Streptococcus pneumoniae isolated from inpatients and outpatients at Beijing Children's Hospital.

BACKGROUND: Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. METHODS: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). RESULTS: The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). CONCLUSIONS: Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.

Regional lymph node mapping in patients with penile cancer undergoing radical inguinal lymph node dissection - a retrospective cohort study.

BACKGROUND: Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. METHODS: A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student's t test and Kaplan-Meier survival analysis were used. RESULTS: ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. CONCLUSIONS: The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.

Surface Patterning of Metal Zinc Electrode with an In-Region Zincophilic Interface for High-Rate and Long-Cycle-Life Zinc Metal Anode.

The undesirable dendrite growth induced by non-planar zinc (Zn) deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially impede the practical application of rechargeable aqueous Zn metal batteries (ZMBs). Herein, we present a strategy for achieving a high-rate and long-cycle-life Zn metal anode by patterning Zn foil surfaces and endowing a Zn-Indium (Zn-In) interface in the microchannels. The accumulation of electrons in the microchannel and the zincophilicity of the Zn-In interface promote preferential heteroepitaxial Zn deposition in the microchannel region and enhance the tolerance of the electrode at high current densities. Meanwhile, electron aggregation accelerates the dissolution of non-(002) plane Zn atoms on the array surface, thereby directing the subsequent homoepitaxial Zn deposition on the array surface. Consequently, the planar dendrite-free Zn deposition and long-term cycling stability are achieved (5,050 h at 10.0 mA cm-2 and 27,000 cycles at 20.0 mA cm-2). Furthermore, a Zn/I2 full cell assembled by pairing with such an anode can maintain good stability for 3,500 cycles at 5.0 C, demonstrating the application potential of the as-prepared ZnIn anode for high-performance aqueous ZMBs.

A unified view on enzyme catalysis by cryo-EM study of a DNA topoisomerase.

The theories for substrate recognition in enzyme catalysis have evolved from lock-key to induced fit, then conformational selection, and conformational selection followed by induced fit. However, the prevalence and consensus of these theories require further examination. Here we use cryogenic electron microscopy and African swine fever virus type 2 topoisomerase (AsfvTop2) to demonstrate substrate binding theories in a joint and ordered manner: catalytic selection by the enzyme, conformational selection by the substrates, then induced fit. The apo-AsfvTop2 pre-exists in six conformers that comply with the two-gate mechanism directing DNA passage and release in the Top2 catalytic cycle. The structures of AsfvTop2-DNA-inhibitor complexes show that substantial induced-fit changes occur locally from the closed apo-conformer that however is too far-fetched for the open apo-conformer. Furthermore, the ATPase domain of AsfvTop2 in the MgAMP-PNP-bound crystal structures coexist in reduced and oxidized forms involving a disulfide bond, which can regulate the AsfvTop2 function.