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AIM: To observe the efficacy of simplified one-step thermokeratoplasty for the treatment of severe acute corneal hydrops in keratoconus. METHODS: In this retrospective, noncomparative clinical study, 10 patients (10 eyes) with acute hydrops in keratoconus were treated with simplified one-step thermokeratoplasty. Pain, changes in the corneal curvature, thickness, and size and morphology of the Descemet membrane breaks were detected before and after surgery. Eight patients were successfully treated using modified deep anterior lamellar keratoplasty (DALK). Graft transparency, visual acuity, and immunological rejection were evaluated for 6 to 12mo. RESULTS: Pain and corneal oedema were promptly alleviated, and the intrastromal ruptures diminished within 3 to 6wk after thermokeratoplasty. At 3 to 6wk after corneal oedema was faded, Descemet membrane breaks and intrastromal ruptures were healed. Two patients did not undergo subsequent corneal transplantation after thermokeratoplasty. Eight patients underwent DALK successfully and safely after thermokeratoplasty, without corneal perforation. Central corneal opacity faded or disappeared within 6mo. The mean best-corrected visual acuity was increased to 20/30 at 12 mo after DALK. No one was observed with any immune rejection. CONCLUSION: One-step thermokeratoplasty can successfully and efficiently accelerate the absorption of prominent corneal oedema in severe acute hydrops patients. This simple procedure with no complications can be performed in the emergency department by residents. This method can improve the safety of DALK and obtain good postoperative vision. Long-term management of acute corneal hydrops using simplified one-step thermokeratoplasty seems promising.

Phenotypic plasticity displayed by an animal in response to different environmental conditions is supposedly crucial for its survival and reproduction. The female adults of some ant lineages display phenotypic plasticity related to reproductive role. In pharaoh ant queens, insemination induces substantial physiological/behavioral changes and implicates remarkable gene regulatory network (GRN) shift in the brain. Here, we report a neuropeptide neuroparsin A (NPA) showing a conserved expression pattern associated with reproductive activity across ant species. Knock-down of NPA in unmated queen enhances ovary activity, whereas injection of NPA peptide in fertilized queen suppresses ovary activity. We found that NPA mainly affected the downstream gene JHBP in the ovary, which is positively regulated by NPA and suppression of which induces elevated ovary activity, and shadow which is negatively regulated by NPA. Furthermore, we show that NPA was also employed into the brain–ovary axis in regulating the worker reproductive changes in other distantly related species, such as Harpegnathos venator ants. Some female ants display phenotypic plasticity related to reproduction, such as the transition between gyne and queen castes. This study shows that the neuropeptide neuroparsin A mediates substantial physiological changes in response to insemination across ant species, acting via ovarian endocrine pathways. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to construct a standardized health risk assessment index system (HRAIS) under the guidance of general health and facilitate the family doctors to carry out chronic disease management. Methods: Available chronic disease surveillance systems and indexes were reviewed to identify potential indexes. The Delphi method was performed to establish the HRAIS, and the analytic hierarchy process was used to calculate the index weight. Results: HRAIS included four first-level indexes and 38 second-level indexes. The authority coefficient was 0.86. The Kendall's W for the two rounds of Delphi consultation were 0.202 and 0.210 (p < 0.001). The weights of the first-level indexes from high to low were physiological health (0.409), psychosocial health (0.290), health-related behaviors (0.205), and environment (0.097). Thus, HRAIS is a multi-dimension and multi-index tool, which can be used as a guideline for family doctors in early screening, early intervention, and classified management of main chronic diseases.

mRNA methylation modification, including N6-methyladenosine (m6A), N5-methylcytidine (m5C) and N1-methyladenosine (m1A), etc., represents more than 60% of all mRNA modifications and varies distribution on mRNA. “Writers” “erasers” “readers” participate in the dynamic and reversible biological process of mRNA methylation modification, which can lead to tumor, virus infection, metabolism diseases, heart or nervous system diseases, etc. when abnormalities occur in a certain link. At present, there are many methylation modification detection technologies, among which the most popular one is high-throughput sequencing.

Abstract Background The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear. Methods Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein–protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan–Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database. Results In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues. Conclusion We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.

PurposeTo explore the composition of the ocular microbiome in patients with Meibomian gland dysfunction (MGD) using metagenomic nanopore sequencing.MethodsA total of 98 participants were recruited from September to December 2021, including 86 patients with MGD and 12 controls. Symptoms and signs of dry eye were assessed, and bacterial samples in the conjunctival sac (CS) and meibomian gland (MG) secretions were then identified by bacterial culture identification and metagenomic nanopore sequencing.ResultsThe positive rate of CS bacterial culture in the MGD group was significantly higher than that in the normal group. A more complex composition of bacterial genera was detected in the mild and moderate MGD groups than in the control. However, the severe MGD groups had the simplest composition of bacteria. Metagenomic nanopore sequencing detected more species of bacteria than traditional culture.ConclusionThe CS and MG of MGD patients may have different degrees of bacterial microbiota imbalance. Metagenomic nanopore sequencing technology provides a new way for us to understand the composition of “real-world” ocular surface microorganisms.

This study presents new geochronological and geochemical data for Early Cretaceous volcanic rocks in the southern margin of the North China Craton (NCC), to discuss the crust–mantle interaction. The studied rocks include pyroxene andesites from Daying Formation, hornblende andesites and andesites from Jiudian Formation, and rhyolites from a hitherto unnamed Formation. These rocks formed in Early Cretaceous (138–120 Ma), with enrichment in light rare earth elements (REE), depletion in heavy REE and arc-like trace elements characteristics. Pyroxene andesites show low SiO2 contents and enriched Sr–Nd–Pb–Hf isotopic compositions, with orthopyroxene phenocryst and Paleoproterozoic (2320–1829 Ma) inherited zircons, suggesting that they originated from lithospheric mantle after metasomatism with NCC lower crustal materials. Hornblende andesites have low SiO2 contents and high Mg# (Mg# = 100 Mg/(Mg + Fe2+)) values, indicating a lithospheric-mantle origin. Considering the distinct whole-rock Sr isotopic compositions we divide them into two groups. Among them, the low (87Sr/86Sr)i andesites possess amount inherited Neoarchean to Neoproterozoic (2548–845 Ma) zircons, indicating the origin of lithospheric mantle with addition of Yangtze Craton (YC) and NCC materials. In comparison, the high (87Sr/86Sr)i andesites, with abundant Neoarchean–Paleozoic inherited zircons (3499–261 Ma), are formed by partial melting of lithospheric mantle with incorporation of NCC supracrustal rocks and YC materials. Rhyolites have extremely high SiO2 (77.63–82.52 wt.%) and low total Fe2O3, Cr, Ni contents and Mg# values, combined with ancient inherited zircon ages (2316 and 2251 Ma), suggesting an origin of NCC lower continental crust. Considering the presence of resorption texture of quartz phenocryst, we propose a petrogenetic model of ‘crystal mushes’ for rhyolites prior to their eruption. These constraints record the intense crust–mantle interaction in the southern margin of the NCC. Given the regional data and spatial distribution of Early Cretaceous rocks within NCC, we believe that the formation of these rocks is related to the contemporaneous far-field effect of the Paleo-Pacific Plate.

Background: The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 210 million individuals globally and resulted in over 4 million deaths since the first report in December 2019. The early use of traditional Chinese medicine (TCM) for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have a wide application in treating infectious and non-infectious diseases. Polygonum cuspidatum Sieb. et Zucc. (P. cuspidatum), is an important Traditional Chinese Medicine with actions of clearing away heat and eliminating dampness, draining the gallbladder to relieve jaundice, removing blood stasis to alleviate pain, resolving phlegm and arrest cough. In the search for anti-SARS-CoV-2, P. cuspidatum was recommended as as a therapeutic drug of COVID-19 pneumonia.In this study, we aimed to identifies P. cuspidatum is the potential broad-spectrum inhibitor for the treatment of coronaviruses infections. Methods: In the present study , we infected human malignant embryonal rhabdomyoma (RD) cells with the OC43 strain of the coronavirus, which represent an alternative model for SARS-CoV-2 and then employed the cell viability assay kit for the antiviral activity. We combined computer aided virtual screening to predicte the binding site and employed Surface plasmon resonance analysis (SPR) to comfirm the interaction between drugs and coronavirus. We employed fluorescence resonance energy transfer technology to identify drug’s inhibition in the proteolytic activity of 3CLpro and Plpro. Results: Based on our results, polydatin and resveratrol derived from P. cuspidatum significantly suppressed HCoV-OC43 replication. 50% inhibitory concentration (IC50) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 μm, respectively. IC50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 μM, respectively. Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein. Conclusions: we identified the antiviral activity of flavonoids polydatin and resveratrol on RD cells. Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases. In summary, this study identifies P. cuspidatum as the potential broad-spectrum inhibitor for the treatment of coronaviruses infections.

ObjectiveThis study aimed to assess the quality of the clinical practice guidelines on psychological distress among cancer patients and provide users with recommendations for coping with psychological distress.MethodsA systematic search of relevant clinical practice guidelines was undertaken to identify and select the clinical practice guidelines related to psychological distress among cancer patients. Literature databases were searched in PubMed, Web of Science, Excerpta Medica Database, the Cumulative Index to Nursing & Allied Health Literature, China Biology Medicine, China National Knowledge Infrastructure, WanFang and Weipu Journal Database. The guideline databases include Yimaitong Guidelines Network, National Guideline Clearinghouse, National Institute for Health and Clinical Excellence, American Society of Clinical Oncology (ASCO), New Zealand Guidelines Group, Scottish Intercollegiate GuidelinesNetwork, American Psychological Association, Registered Nurses’ Association of Ontario and Cancer Care Ontario (CCO). Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.ResultsSix clinical practice guidelines were included and assessed for critical evaluation. The median score for the scope and purpose domain was 71.5% (IQR 64%-77.25%), the stakeholder involvement domain was 65% (IQR 47.5%-74.5%), the rigour of the development domain was 61.5% (IQR 45.5%-85.25%), the clarity of the presentation domain was 91% (IQR 72.25%-94.5%), the applicability domain was 70% (IQR 33%-78.75%), and the editorial independence domain was 48.84% (IQR 61.75%-95%). Four guidelines (ASCO, 2014; Canadian Association of Psychosocial Oncology, 2015; NCCN, 2020, and CCO, 2016) were classified as “recommended,” and the remaining (European Palliative Care Research Collaborative and Chinese Psychosocial Oncology Society) were “recommended with modifications,” especially in the domains of Stakeholder involvement, rigour of development, and applicability. The inter-rater consistency of each domain showed moderate level (0.52–0.90) analyzing by intraclass correlation.ConclusionsThe clinical practice guidelines on psychological distress among cancer patients varied in quality, and there were discrepancies in terms of the recommendations and recommendation grades. These findings could contribute to improving the quality of clinical practice guidelines on psychological distress, and enable the development and implementation of evidence-based guidelines for cancer patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42020209204.

Estrogen and progesterone coupled with locally produced signaling molecules are essential for embryo implantation. However, the hierarchical landscape of the molecular pathways that governs this process remains largely unexplored. Here we show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK signaling, is predominately localized in the nuclei in the periimplantation mouse uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor (PR) expression and progesterone resistance, which derails normal uterine receptivity, leading to complete implantation failure in mice. Notably, the PR expression defects are attributed to the limited estrogen receptor α (ERα) activation in uterine stroma. Further analysis reveals that nuclear Shp2, rather than cytosolic Shp2, promotes the ERα transcription activity. This function is achieved by enhancing the Src kinase-mediated ERα tyrosine phosphorylation, which facilitates ERα binding to Pgr promoter in an ERK-independent manner in periimplantation uteri. Besides uncovering a regulatory mechanism, this study could be clinically relevant to dysfunctional ERα-caused endometrial disorders in women.

PurposeTo assess air pollution-induced changes on ocular surface and tear cytokine levels.MethodsAs a prospective multicenter cohort study, 387 dry eye disease (DED) participants were recruited from five provinces in China and underwent measurements of ocular surface disease index (OSDI), Schirmer’s I test (ST), tear meniscus height (TMH), tear film break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland (MG) function, and tear cytokines. The associations between ocular surface parameters and exposure to particulate matter (PM), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2) for 1 day, 1 week, and 1 month before the examination were analyzed in single- and multi-pollutant models adjusted for confounding factors.ResultsIn the multi-pollutant model, the OSDI score was positively correlated with PM with diameter ≤2.5 μm (PM2.5), O3, and SO2 exposure [PM2.5: β (1 week/month) = 0.229 (95% confidence interval (CI): 0.035–0.424)/0.211 (95% CI: 0.160–0.583); O3: β (1 day/week/month) = 0.403 (95% CI: 0.229–0.523)/0.471 (95% CI: 0.252–0.693)/0.468 (95% CI: 0.215–0.732); SO2: β (1 day/week) = 0.437 (95% CI: 0.193–0.680)/0.470 (95% CI: 0.040–0.901)]. Tear secretion was negatively correlated with O3 and NO2 exposures but positively correlated with PM2.5 levels. Air pollutants were negatively correlated with TBUT and positively related with CFS score. Besides SO2, all other pollutants were associated with aggravated MG dysfunction (MG expression, secretion, and loss) and tear cytokines increasement, such as PM2.5 and interleukin-8 (IL-8) [β (1 day) = 0.016 (95% CI: 0.003–0.029)], PM with diameter ≤10 μm (PM10) and IL-6 [β (1 day) = 0.019 (95% CI: 0.006–0.033)], NO2 and IL-6 [β (1 month) = 0.045 (95% CI: 0.018–0.072)], among others. The effects of air pollutants on DED symptoms/signs, MG functions and tear cytokines peaked within 1 week, 1 month, and 1 day, respectively.ConclusionIncreased PM2.5, O3, and SO2 exposures caused ocular discomfort and damage with tear film instability. PM10 exposure led to tear film instability and ocular injury. PM, O3, and NO2 exposures aggravated MG dysfunction and upregulated tear cytokine levels. Therefore, each air pollutant may influence DED via different mechanisms within different time windows.

This study aimed to investigate the association of between previously neglected oval cells located in the corneal vortex and dry eye disease (DED). This was an observational, prospective study involving 168 patients with different degrees of DED. In vivo confocal microscopy was used to observe the corneal subbasal nerves and Langerhans cells (LCs) in the corneal vortex and periphery. Bright and oval cells were also observed in the corneal vortex. An artificial intelligence technique was used to generate subbasal nerve fiber parameters. The patients were divided into the three groups based on the presence of inflammatory cells. Group 2 patients showed a significant increase in the corneal peripheral nerve maximum length and average corneal peripheral nerve density. Patients in group 3 had more LCs than other patients. A bright and oval cell was identified in the corneal vortex, which might be a type of immature LC related to the disease severity of DED.

PurposeThe study assessed the validity of impression cytology (IC) and in vivo confocal microscopy (IVCM) of lip mucosa compared with labial gland biopsy, anti-Sjögren’s syndrome A (SSA)/Ro antibody status, and classification criteria in suspected primary Sjögren’s syndrome (pSS) patients.MethodsClinically suspected pSS patients (n = 201) were enrolled consecutively and were divided into pSS (n = 56) and control (n = 145, only with dryness) groups according to the American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria. All patients underwent lip mucosa IC (inflammatory cell density) and IVCM (epithelium/intrinsic layer thickness and labial gland density/diameter) analyses. The associations between IC/IVCM parameters and clinical/laboratory results were analyzed.ResultsThe absolute agreement between positive lip mucosal IC (≥50 cells/4 mm2) and the ACR-EULAR criteria (94.5%)/labial gland biopsy (95.5%) was good, with sensitivities of 82.1 and 85.2%, respectively, and a specificity of 99.3%. Compared with controls, IVCM revealed significant lip mucosal atrophy and glandular decreases in the pSS group (all P = 0.000). The sensitivities for diagnosing pSS corresponding to a lamina propria thickness ≤128 μm and a gland diameter ≤114 μm were 85.7 and 89.3%; the specificities were 90.3 and 95.9%, respectively. A combination of positive IC/IVCM and anti-SSA/Ro antibody results showed a high predictive value for diagnosing pSS.ConclusionsIC and IVCM could detect distinctive cellular and morphological changes in the lip mucosa of patients with pSS. These noninvasive and easy-to-perform examinations may be an alternative to labial gland biopsy for diagnosing pSS.

AIM: To investigate the concentration of leptin in tears and its correlation with dry eye symptoms and signs. METHODS: The study enrolled individuals (n=39) responding to an advertising or dry eye patients (n=58) from the Ophthalmology Department. Tear samples were collected for leptin concentration measuring. Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear break up time (TBUT), cornea fluorescein staining, Schirmer test (ST) and impression cytology (IC) were assessed. Leptin concentration in tears of dry eye patients and healthy controls, and its correlation with clinical features of dry eye disease (DED) were analyzed. RESULTS: Age, body mass index (BMI), OSDI scores and cornea fluorescein staining scores showed a negative correlation with leptin concentration in tears (r=-0.340, P=0.001; r=-0.332, P=0.001; r=-0.258, P=0.011; r=-0.424, P

PurposeLess was known about globular cells which were a type of dendritic cells (DCs) in cornea. We aimed to investigate the morphological and distribution characteristics of globular cells in corneal vortex and their clinical correlations with ocular surface.MethodsCase records of patients who underwent in vivo confocal microscopy (IVCM) were evaluated retrospectively. The morphology and distribution features of globular cells in cornea nerve vortex and their co-existence status with Langerhans cells (LCs) were analyzed. Data of ocular surface symptoms and signs were collected and their correlations with globular cells distribution patterns and dendritic forms were performed. Dry eye patients without LCs were treated with preservative-free artificial tears, while patients with LCs were treated with artificial tears and fluoromethalone until the activated LCs disappeared.ResultsA total of 836 eyes from 451 individuals were included. Three distribution patterns of globular cells in vortex were investigated, type 1 scattered globular cells (57.66%), type 2 large amounts of globular cells (≥50 cells) gathering in vortex and along some fixed vortex direction horizontally (13.52%) and type 3 no globular cells (28.83%). Their location and cell count altered slightly in the follow-ups but would not disappear. LCs could co-exist with globular cells and could fade after treatment. The type 2 distribution pattern was associated with older age (p = 0.000) and higher upper eyelid Meiboscore (p = 0.006). Dendritic globular cells had higher Meiboscore than Non-dendritic forms.ConclusionsGlobular cells had characteristic distribution patterns and biological features different from LCs. They were associated with long-term irritation of the meibomian gland dysfunction.

The ultrafine-grained (UFG) CrCoNi medium entropy alloys (MEAs) with excellent mechanical and tribological performances were fabricated by combining rolling deformation and annealing treatment. The microstructures of CrCoNi MEAs were characterized by electron backscatter diffraction (EBSD) and transmission electron microscope (TEM). The results show that the materials annealed at 650 ℃ for 10 min after cryogenic rolling display a yield strength as high as 1135 MPa and a graceful uniform ductility of 14.1%. Another group of materials rolled at room temperature followed by annealing at 650 ℃ for 20 min exhibit a yield strength of 987 MPa and an improved ductility of 18.6%. In addition, the grains of CrCoNi medium entropy alloys after above treatment are greatly refined to an average grain size of 0.81 μm and 0.92 μm respectively. The ultra-high strength is due to the grain boundary strengthening of high angle boundaries and dislocation strengthening of low angle boundaries. Remarkably, such UFG MEAs exhibit high wear resistance.

Background: This study aimed to investigate the TP53 mutation, its potential immune features, its prognostic value, and its impact on immune infiltration in patients with breast cancer (BC).Methods: We downloaded the somatic mutation data and clinicopathologic features of BC patients from the TCGA GDC database, UCSC Xena platform, and International Cancer Genome Consortium (ICGC) database. The association between the TP53 mutation, clinicopathology features, and overall survival (OS) in BC patients was analyzed. We evaluated the potential role of the TP53 mutation in the immune therapy response, including the tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE). Moreover, ESTIMATE was employed to assess the ImmuneScore and StromalScore in BC patients. We also explored immunocyte infiltration related to the TP53 mutation and its potential mechanism. Immunohistochemistry (IHC) was performed to validate the association between the expression of CXCL1, CXCL10, and CCL20 and TP53 status.Results: We found that the TP53 mutation was significantly associated with the shorter OS (p = 0.038) and was also an independent predictive factor of OS for BC patients (p < 0.001). Compared to that in the wild type group, the TP53-mutant group showed a higher TMB value (P< 0.001), MSI value (p = 0.077), and TIDE value (p < 0.001) with respect to BC patient immunotherapy. In addition, the ImmuneScore and StromalScore were both significantly increased in the TP53-mutant group (ImmuneScore: p < 0.001; StromalScore: p = 0.003). The results of CIBERSORT suggested that the TP53 mutation significantly promoted the infiltration of Tregs, T helper cells, and M0-type macrophages. KEGG and GSEA enrichment results suggested that the IL-17 signaling pathway and antigen processing and presentation pathways were significantly enriched in the TP53-mutant group. Importantly, based on IHC results of immune-related hub-genes, the chemokines CXCL1, CXCL10, and CCL20 were significantly upregulated in the TP53-mutant group in BC patients.Conclusion: These results indicate that a TP53 mutation might serve as a biomarker for BC prognosis and is related to immunocyte infiltration in the tumor microenvironment.

The males ability to reproduce is completely dependent on Sertoli cells. However, the mechanisms governing the functional integrity of Sertoli cells have remained largely unexplored. Here, we demonstrate that deletion of Shp2 in Sertoli cells results in infertility in mice. In Shp2 knockout mice (SCSKO), a normal population of Sertoli cells was observed, but the blood-testis barrier (BTB) was not formed. Shp2 ablation initiated the untimely and excessive differentiation of spermatogonial stem cells (SSCs) by disturbing the expression of paracrine factors. As a consequence, the process of spermatogenesis was disrupted, and the germ cells were depleted. Furthermore, Shp2 deletion impaired the cell junctions of the primary Sertoli cells and failed to support the clonal formation of SSCs co-cultured with SCSKO Sertoli cells. As expected, Shp2 restoration largely restores the cell junctions of the primary Sertoli cells and the clonal formation of SSCs. To identify the underlying mechanism, we further demonstrated that the absence of Shp2 suppressed Erk phosphorylation, and thus, the expression of follicle-stimulating hormone (FSH)- and testosterone-induced target genes. These results collectively suggest that Shp2 is a critical signaling protein that is required to maintain Sertoli cell function and could serve as a novel target for male infertility therapies.