Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis.

Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.

Depression score mediate the association between a body shape index and infertility in overweight and obesity females, NHANES 2013-2018.

BACKGROUND: Overweight and obese females demonstrate a significantly increased risk of anovulatory infertility. This study aims to investigate whether depression score could mediate the association between a body shape index (ABSI) and infertility, especially in overweight and obese population. METHODS: We included 5431 adult female Americans from the National Health and Nutrition Examination Survey (NHANES, 2013-2018) database. ABSI manifested the body shape using waist circumference, weight, and height. Infertility or fertility status was defined by interviewing female participants aged ≥ 18 through the reproductive health questionnaires. Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) with total scores between 0 and 27. To investigate the association of infertility with ABSI and other individual components, survey-weighted multivariable logistic regression was performed. Mediation analysis of PHQ-9 score was conducted to disentangle the pathways that link ABSI to infertility among the NHANES participants. RESULTS: 596 (10.97%) females were categorized with having infertility among 5431 participants. Participants with infertility showed higher ABSI and PHQ-9 score, appearing greater population proportion with depression symptoms. In the multivariable logistic regression model, ABSI (adjusted odds ratio = 0.14, 95% CI: 0.04 to 0.50) and PHQ-9 (adjusted odds ratio = 1.04, 95% CI: 1.01 to 1.07) were positively associated with infertility. PHQ-9 score was estimated to mediate 0.2% (P = 0.03) of the link between ABSI and infertility in all individuals, but to mediate 13.5% (P < 0.01) of the ABSI-infertility association in overweight and obese adult females. CONCLUSION: The association between ABSI and infertility seems to be mediated by depression symptoms scored by PHQ-9, especially in those adult females with overweigh and obesity. Future studies should be implemented to further explore this mediator in ABSI-infertility link.

SPAG6 c.900 T>C affects boar semen quality and blood-testis barrier function by creating a new splice acceptor site.

Sperm associated antigen 6 (SPAG6) acts as a scaffolding protein in the center of the flagellar axoneme and has an impact on the maturation of the motility of mammalian sperm flagella and the maintenance of sperm structure. In our previous research, SPAG6 c.900 T>C in exon 7 and exon 7 skipped transcript was identified by analyzing RNA-seq data of testicular tissues from 60 day (sexually immature) and 180 day (sexually mature) Large White boars. Herein, we found porcine SPAG6 c.900 T>C to be associated with semen quality traits in Duroc, Large White and Landrace pigs. SPAG6 c.900 C can generate a new splice acceptor site, inhibit the occurrence of SPAG6 exon 7 skipping to a certain extent, thereby promote the growth of Sertoli cells and maintain the normal blood-testis barrier function. This study provides new insights into the molecular regulation of spermatogenesis and a new genetic marker for the improvement of semen quality in pigs.

Nonsynonymous SNPs within C7H15orf39 and NOS2 are associated with boar semen quality.

Spermatogenesis is the developmental process that produces spermatozoa. The aim of this study was to investigate the single nucleotide polymorphisms (SNPs) within C7H15orf39 and NOS2 genes and to determine the correlations between two SNPs and semen quality in Duroc boars (n = 604). The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method was used for genotyping the selected two nonsynonymous SNPs. The significant correlation was observed between two SNPs (rs80969873: g.58385473 G > A within C7H15orf39; rs325865291: g.44175445 G > A within NOS2) and semen traits in Duroc boars. This study indicates the SNPs in C7H15orf39 and NOS2 may be the potential molecular marker for improving the semen quality traits in Duroc boars.

Twenty years of ocean observations with China Argo.

The international Argo program, a global observational array of nearly 4 000 autonomous profiling floats initiated in the late 1990s, which measures the water temperature and salinity of the upper 2 000 m of the global ocean, has revolutionized oceanography. It has been recognized one of the most successful ocean observation systems in the world. Today, the proposed decade action "OneArgo" for building an integrated global, full-depth, and multidisciplinary ocean observing array for beyond 2020 has been endorsed. In the past two decades since 2002, with more than 500 Argo deployments and 80 operational floats currently, China has become an important partner of the Argo program. Two DACs have been established to process the data reported from all Chinese floats and deliver these data to the GDACs in real time, adhering to the unified quality control procedures proposed by the Argo Data Management Team. Several Argo products have been developed and released, allowing accurate estimations of global ocean warming, sea level change and the hydrological cycle, at interannual to decadal scales. In addition, Deep and BGC-Argo floats have been deployed, and time series observations from these floats have proven to be extremely useful, particularly in the analysis of synoptic-scale to decadal-scale dynamics. The future aim of China Argo is to build and maintain a regional Argo fleet comprising approximately 400 floats in the northwestern Pacific, South China Sea, and Indian Ocean, accounting for 9% of the global fleet, in addition to maintaining 300 Deep Argo floats in the global ocean (25% of the global Deep Argo fleet). A regional BGC-Argo array in the western Pacific also needs to be established and maintained.

AR regulates porcine immature Sertoli cell growth via binding to RNF4 and miR-124a.

Sertoli cells are the only somatic cells in the seminiferous epithelium which directly contact with germ cells. Sertoli cells exhibit polarized alignment at the basal membrane of seminiferous tubules to maintain the microenvironment for growth and development of germ cells, and therefore play a crucial role in spermatogenesis. Androgens exert their action through androgen receptor (AR) and AR signalling in the testis is essential for maintenance of spermatogonial numbers, blood-testis barrier integrity, completion of meiosis, adhesion of spermatids and spermiation. In the present study, we demonstrated that AR gene could promote the proliferation of immature porcine Sertoli cells (ST cells) and the cell cycle procession, and accelerate the transition from G1 phase into S phase in ST cells. Meanwhile, miR-124a could affect the proliferation and cell cycle procession of ST cells by targeting 3'-UTR of AR gene. Furthermore, AR bound to the RNF4 via AR DNA-binding domain (DBD) and we verified that RNF4 was necessary for AR to regulate the growth of ST cells. Above all, this study suggests that AR regulates ST cell growth via binding to RNF4 and miR-124a, which may help us to further understand the function of AR in spermatogenesis.

[Inhibitory effect of Ningmitai Capsules on the proliferation and biofilm formation of Staphylococcus sp. and Escherichia coli].

OBJECTIVE: To evaluate the inhibitory effect of Ningmitai Capsules (NMTC) on the proliferation and in vitro biofilm formation of Staphylococcus sp. and Escherichia coli (E. coli). METHODS: Using the gradient dilution method, we determined the minimum inhibitory concentration (MIC) of NMTC against Staphylococcus epidermidis (S. epidermids) 1457, Staphylococcus aureus (S. aureus) NCTC8325-4/ Newman/ MU50 and E. coli ATCC25922/ CF073, and observed the effects of different concentrations of NMTC on their biofilm formation in vitro under the electron microscope. RESULTS: NMTC significantly suppressed the proliferation of S. epidermidis 1457, S. aureus NCTC8325-4/ Newman/ MU50 and E. coli ATCC25922/CF073 at an MIC of 20 mg/ml as well as their biofilm formation in vitro. CONCLUSIONS: Ningmitai Capsules can inhibit the proliferation and in vitro biofilm formation of S. epidermids and E. coli, and has a comprehensive antibacterial effect.

Circum-Antarctic bottom water formation mediated by tides and topographic waves.

The downslope plumes of dense shelf water (DSW) are critical for the formation of Antarctic Bottom Water (AABW), and thus to the exchange of heat and carbon between surface and abyssal ocean. Previous studies have shown that tides and overflow-forced topographic Rossby waves (TRWs) may have strong impact on the downslope transport of DSW, but it remains unclear how the combined action of these two processes influence the descent processes of DSW, and of the resulting AABW properties. Here, with a synthesis of historical in situ observations and a set of numerical model experiments, we show that tides and TRWs play comparable roles in AABW formation: they both act to accelerate DSW descent to the abyss, leading to the formation of colder and denser AABW. Yet, tides have little impact on AABW formation unless the continental slope is steep enough to suppress TRW generation. We further characterize the dynamical regimes of dense overflows around the entire Antarctic continent based on the relative importance of TRWs versus tides. These findings highlight the pervasive role of high-frequency processes, which are not well represented in the present climate models, in the formation of AABW, and thus in the global overturning circulation.

An androgen receptor-based signature to predict prognosis and identification of ORC1 as a therapeutical target for prostate adenocarcinoma.

Background: Aberrant activation of androgen receptor (AR) signaling plays a crucial role in the progression of prostate adenocarcinoma (PRAD) and contributes significantly to the development of enzalutamide resistance. In this study, we aimed to identify a novel AR-driven signature that can predict prognosis and endows potentially reveal novel therapeutic targets for PRAD. Methods: The Seurat package was used to preprocess the single-cell RNA sequencing (scRNA-seq). Differentially expressed genes were visualized using limma and pheamap packages. LASSO and multi-variate Cox regression models were established using glmnet package. The package "Consensus Cluster Plus" was utilized to perform the consensus clustering analysis. The biological roles of origin recognition complex subunit 1 (ORC1) in PRAD were determined by gain- and loss-of-function studies in vitro and in vivo. Result: We characterized the scRNA-seq data from GSE99795 and identified 10 AR-associated genes (ARGs). The ARGs model was trained and validated in internal and external cohorts. The ARGs were identified as an independent hazard factor in PRAD and correlated with clinical risk characteristics. In addition, the ARGs were found to be correlated with somatic tumor mutation burden (TMB) levels. Two groups that have distinct prognostic and molecular features were identified through consensus clustering analysis. ORC1 was identified as a critical target among these ARGs, and it ORC1 promoted proliferation and stem-like properties of PRAD cells. Chromatin immunoprecipitation (ChIP)-qPCR assay confirmed that AR could directly bind the promoter of ORC1. Activated AR/ORC1 axis contributed to enzalutamide resistance, and targeting ORC1 rendered PRAD cells more susceptible to enzalutamide. Conclusions: This study defines an AR-driven signature that AR activates ORC1 expressions to promote PRAD progression and enzalutamide resistance, which may provide novel targets for PRAD treatment.

Atlantic origin of the increasing Asian westerly jet interannual variability.

The summer Eurasian westerly jet is reported to become weaker and wavier, thus promoting the frequent weather extremes. However, the primary driver of the changing jet stream remains in debate, mainly due to the regionality and seasonality of the Eurasian jet. Here we report a sharp increase, by approximately 140%, in the interannual variability of the summertime East Asian jet (EAJ) since the end of twentieth century. Such interdecadal change induces considerable changes in the large-scale circulation pattern across Eurasia, and consequently weather and climate extremes including heatwaves, droughts, and Asian monsoonal rainfall regime shifts. The trigger mainly emerges from preceding February North Atlantic seesaw called Scandinavian pattern (contributing to 81.1 ± 2.9% of the enhanced EAJ variability), which harnesses the "cross-seasonal-coupled oceanic-atmospheric bridge" to exert a delayed impact on EAJ and thus aids relevant predictions five months in advance. However, projections from state-of-the-art models with prescribed anthropogenic forcing exhibit no similar circulation changes. This sheds light on that, at the interannual timescale, a substantial portion of recently increasing variability in the East Asian sector of the Eurasian westerly jet arises from unforced natural variability.

Deep Learning Classification of Angle Closure based on Anterior Segment OCT.

PURPOSE: To assess the performance and generalizability of a convolutional neural network (CNN) model for objective and high-throughput identification of primary angle-closure disease (PACD) as well as PACD stage differentiation on anterior segment swept-source OCT (AS-OCT). DESIGN: Cross-sectional. PARTICIPANTS: Patients from 3 different eye centers across China and Singapore were recruited for this study. Eight hundred forty-one eyes from the 2 Chinese centers were divided into 170 control eyes, 488 PACS, and 183 PAC + PACG eyes. An additional 300 eyes were recruited from Singapore National Eye Center as a testing data set, divided into 100 control eyes, 100 PACS, and 100 PAC + PACG eyes. METHODS: Each participant underwent standardized ophthalmic examination and was classified by the presiding physician as either control, primary angle-closure suspect (PACS), primary angle closure (PAC), or primary angle-closure glaucoma (PACG). Deep Learning model was used to train 3 different CNN classifiers: classifier 1 aimed to separate control versus PACS versus PAC + PACG; classifier 2 aimed to separate control versus PACD; and classifier 3 aimed to separate PACS versus PAC + PACG. All classifiers were evaluated on independent validation sets from the same region, China and further tested using data from a different country, Singapore. MAIN OUTCOME MEASURES: Area under receiver operator characteristic curve (AUC), precision, and recall. RESULTS: Classifier 1 achieved an AUC of 0.96 on validation set from the same region, but dropped to an AUC of 0.84 on test set from a different country. Classifier 2 achieved the most generalizable performance with an AUC of 0.96 on validation set and AUC of 0.95 on test set. Classifier 3 showed the poorest performance, with an AUC of 0.83 and 0.64 on test and validation data sets, respectively. CONCLUSIONS: Convolutional neural network classifiers can effectively distinguish PACD from controls on AS-OCT with good generalizability across different patient cohorts. However, their performance is moderate when trying to distinguish PACS versus PAC + PACG. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Multi-Dataset Comparison of Vision Transformers and Convolutional Neural Networks for Detecting Glaucomatous Optic Neuropathy from Fundus Photographs.

Glaucomatous optic neuropathy (GON) can be diagnosed and monitored using fundus photography, a widely available and low-cost approach already adopted for automated screening of ophthalmic diseases such as diabetic retinopathy. Despite this, the lack of validated early screening approaches remains a major obstacle in the prevention of glaucoma-related blindness. Deep learning models have gained significant interest as potential solutions, as these models offer objective and high-throughput methods for processing image-based medical data. While convolutional neural networks (CNN) have been widely utilized for these purposes, more recent advances in the application of Transformer architectures have led to new models, including Vision Transformer (ViT,) that have shown promise in many domains of image analysis. However, previous comparisons of these two architectures have not sufficiently compared models side-by-side with more than a single dataset, making it unclear which model is more generalizable or performs better in different clinical contexts. Our purpose is to investigate comparable ViT and CNN models tasked with GON detection from fundus photos and highlight their respective strengths and weaknesses. We train CNN and ViT models on six unrelated, publicly available databases and compare their performance using well-established statistics including AUC, sensitivity, and specificity. Our results indicate that ViT models often show superior performance when compared with a similarly trained CNN model, particularly when non-glaucomatous images are over-represented in a given dataset. We discuss the clinical implications of these findings and suggest that ViT can further the development of accurate and scalable GON detection for this leading cause of irreversible blindness worldwide.

Middle east warming in spring enhances summer rainfall over Pakistan.

The edge of a monsoon region is usually highly sensitive to climate change. Pakistan, which is located on the northern edge of the Indian monsoon, is highly vulnerable to heavy rainfall and has witnessed several debilitating floods exacerbated by global warming in recent years. However, the mechanisms for the frequent Pakistan floods are yet not fully understood. Here, we show that the Middle East is undergoing an increase in land heating during spring, which is responsible for 46% of the intensified rainfall over Pakistan and northwestern India during 1979-2022. This springtime land warming causes a decline in sea level pressure (SLP), which strengthens the meridional SLP gradient between the Middle East and the southern Arabian Sea and drives the changes of low-level jet (LLJ) subsequently. The impact persists into summer and results in a northward shift of the monsoonal LLJ, accompanied by strong positive vorticity in the atmosphere and enhanced moisture supply to Pakistan. Consequently, the transition region between the summer monsoon in South Asia and the desert climate in West Asia is shifted northwestward, posing significantly enhanced risk of floods over Pakistan and northwestern India.

ISG15 suppresses ovulation and female fertility by ISGylating ADAMTS1.

BACKGROUND: ISGylation is a post-translational protein modification that regulates many life activities, including immunomodulation, antiviral responses, and embryo implantation. The exact contribution of ISGylation to folliculogenesis remains largely undefined. RESULTS: Here, Isg15 knockout in mice causes hyperfertility along with sensitive ovarian responses to gonadotropin, such as increases in cumulus expansion and ovulation rate. Moreover, ISG15 represses the expression of ovulation-related genes in an ISGylation-dependent manner. Mechanistically, ISG15 binds to ADAMTS1 via the ISG15-conjugating system (UBA7, UBE2L6, and HERC6), ISGylating ADAMTS1 at the binding sites Lys309, Lys593, Lys597, and Lys602, resulting in ADAMTS1 degradation via a 20S proteasome-dependent pathway. CONCLUSION: Taken together, the present study demonstrates that covalent ISG15 conjugation produces a novel regulatory axis of ISG15-ADAMTS1 that enhances the degradation of ADAMTS1, thereby compromising ovulation and female fertility.

A new ensemble-based targeted observational method and its application in the TPOS 2020.

Ensemble Kalman filter-based targeted observation is one of the best methods for determining the optimal observational array for oceanic buoy deployment. This study proposes a new algorithm suitable for a 'cross-region and cross-variable' approach by introducing a projection operator into the optimization process. A targeted observational analysis was conducted for El Niño-Southern Oscillation (ENSO) events in the tropical western Pacific for the Tropical Pacific Observation System (TPOS) 2020. The prediction target was at the Niño 3.4 region and the first 10 optimal observational sites detected reduced initial uncertainties by 70%, with the best observational array located where the Rossby wave signal dominates. At the vertical level, the most significant contribution was derived from observations near the thermocline. This study provides insights into understanding ENSO-related variability and offers a practical approach to designing an optimal mooring array. It serves as a scientific guidance for designing a TPOS observation network.

A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication.

Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro, and had an IC50 of 18 µM for PLpro inhibition. Compound 1 also had low non-specific reactivity with thiols and reacted with glutathione 1-2 orders of magnitude slower than other commonly used electrophilic warheads. Finally, compound 1 had low toxicity in cells and mice and has a molecular weight of only 247 daltons and consequently has great potential for further optimization. Collectively, these results demonstrate that compound 1 is a promising lead fragment for future PLpro drug discovery campaigns.

BCL2-associated athanogene 6 exon24 contributes to testosterone synthesis and male fertility in mammals.

OBJECTIVES: BCL2-associated athanogene 6 (BAG6) plays critical roles in spermatogenesis by maintaining testicular cell survival. Our previous data showed porcine BAG6 exon24-skipped transcript is highly expressed in immature testes compared with mature testes. The objective of this study is to reveal the functional significance of BAG6 exon24 in mammalian spermatogenesis. MATERIALS AND METHODS: CRISPR/Cas9 system was used to generate Bag6 exon24 knockout mice. Testes and cauda epididymal sperm were collected from mice. TMT proteomics analysis was used to discover the protein differences induced by Bag6 exon24 deletion. Testosterone enanthate was injected into mice to generate a high-testosterone mice model. H&E staining, qRT-PCR, western blotting, vector/siRNA transfection, immunofluorescence, immunoprecipitation, transmission electron microscopy, TUNEL and ELISA were performed to investigate the phenotypes and molecular basis. RESULTS: Bag6 exon24 knockout mice show sub-fertility along with partially impaired blood-testis barrier, increased apoptotic testicular cell rate and abnormal sperm morphology. Endoplasmic reticulum stress occurs in Bag6 exon24-deficient testes and sterol regulatory element-binding transcription factor 2 is activated; as a result, cytochrome P450 family 51 subfamily A member 1 expression is up-regulated, which causes a high serum testosterone level. Additionally, serine/arginine-rich splicing factor 1 down-regulates BAG6 exon24-skipped transcripts in porcine Sertoli cells by binding to 35-51 nt on BAG6 exon24 via its N-terminal RNA-recognition domain. CONCLUSIONS: Our findings reveal the critical roles of BAG6 exon24 in testosterone biosynthesis and male fertility, which provides new insights into the regulation of spermatogenesis and pathogenesis of subfertility in mammals.

CMTM5 inhibits the development of prostate cancer via the EGFR/PI3K/AKT signaling pathway.

Prostate cancer (PCa) endangers the life and health of older men. Most PCa cases develop into castration­resistant PCa (CRPC) within 2 years. At present, the molecular mechanisms of the occurrence and development of PCa and its transformation to CRPC remain unknown. The present study aimed to investigate the role of CKLF­like Marvel transmembrane domain containing family member 5 (CMTM5) in PCa and its molecular mechanism in vitro. PCa tissues and paired adjacent normal prostate tissues from 70 patients were collected to examine the expression levels of CMTM5 and EGFR via immunohistochemistry, reverse transcription­quantitative PCR and western blotting. Then, CMTM5­overexpressing DU145 cells were constructed, and CMTM5 expression in these transfected cells and vector control cells was examined via western blotting. Cell Counting Kit­8 and plate clone formation assays were used to evaluate the proliferation and colony number of CMTM5­overexpressing cells and vector control cells. Then, cell migration and invasion were assessed using wound healing assay, Transwell assay and immunofluorescence analysis with DAPI staining. The effect of CMTM5 on apoptosis and its underlying molecular mechanism were examined using western blotting and flow cytometry. The results demonstrated that CMTM5 expression in PCa tissues and cell lines was significantly downregulated, while EFGR expression was significantly upregulated. The proportion of high CMTM5 expression in PCa tissues was significantly lower compared with that in normal prostate tissues. By contrast, the proportion of high EGFR expression in PCa tissues was significantly increased compared with that in normal prostate tissues. Moreover, CMTM5 overexpression significantly inhibited cell proliferation, migration and invasion, and promoted cell apoptosis compared with vector control cells in vitro. Furthermore, the regulation of PCa by CMTM5 was associated with the downregulation of PI3K/AKT and its downstream Bcl­2 expression, as well as the upregulation of Bax expression. In conclusion, CMTM5 may be an effective tumor suppressor gene for PCa, especially for castration­resistant PCa, by downregulating EGFR and PI3K/AKT signaling pathway components.

Long-term outcomes of radiofrequency ablation vs. partial nephrectomy for cT1 renal cancer: A meta-analysis and systematic review.

Background: Partial nephrectomy (PN) is one of the most preferred nephron-sparing treatments for clinical T1 (cT1) renal cancer, while radiofrequency ablation (RFA) is usually used for patients who are poor surgical candidates. The long-term oncologic outcome of RFA vs. PN for cT1 renal cancer remains undetermined. This meta-analysis aims to compare the treatment efficacy and safety of RFA and PN for patients with cT1 renal cancer with long-term follow-up of at least 5 years. Method: This meta-analysis was performed following the PRISMA reporting guidelines. Literature studies that had data on the comparison of the efficacy or safety of RFA vs. PN in treating cT1 renal cancer were searched in databases including PubMed, Embase, Web of Science, and the Cochrane Library from 1 January2000 to 1 May 2022. Only long-term studies with a median or mean follow-up of at least 5 years were included. The following measures of effect were pooled: odds ratio (OR) for recurrence and major complications; hazard ratio (HR) for progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Additional analyses, including sensitivity analysis, subgroup analysis, and publication bias analysis, were also performed. Results: A total of seven studies with 1,635 patients were finally included. The treatment efficacy of RFA was not different with PN in terms of cancer recurrence (OR = 1.22, 95% CI, 0.45-3.28), PFS (HR = 1.26, 95% CI, 0.75-2.11), and CSS (HR = 1.27, 95% CI, 0.41-3.95) as well as major complications (OR = 1.31, 95% CI, 0.55-3.14) (P > 0.05 for all). RFA was a potential significant risk factor for OS (HR = 1.76, 95% CI, 1.32-2.34, P < 0.001). No significant heterogeneity and publication bias were observed. Conclusion: This is the first meta-analysis that focuses on the long-term oncological outcomes of cT1 renal cancer, and the results suggest that RFA has comparable therapeutic efficacy with PN. RFA is a nephron-sparing technique with favorable oncologic efficacy and safety and a good treatment alternative for cT1 renal cancer.

A self-immolative linker that releases thiols detects penicillin amidase and nitroreductase with high sensitivity via absorption spectroscopy.

This article reports the synthesis and characterization of a novel self-immolative linker, based on thiocarbonates, which releases a free thiol upon activation via enzymes. We demonstrate that thiocarbonate self-immolative linkers can be used to detect the enzymes penicillin G amidase (PGA) and nitroreductase (NTR) with high sensitivity using absorption spectroscopy. Paired with modern thiol amplification technology, the detection of PGA and NTR were achieved at concentrations of 160 nM and 52 nM respectively. In addition, the PGA probe was shown to be compatible with both biological thiols and enzymes present in cell lysates.