The allostery and modification of hGHRH molecules and specific dimer produced significant fertility effect by proliferating and activating in-situ ovarian mesenchymal stem cells.

The negative coordination of growth hormone secretagogue receptor (GHS-R) and growth hormone-releasing hormone receptor (GHRH-R) involves in the repair processes of cellular injury. The allosteric U- or H-like modified GHRH dimer Grinodin and 2Y were comparatively evaluated in normal Kunming mice and hamster infertility models induced by CPA treatment. 1-3-9 µg of Grinodin or 2Y per hamster stem-cell-exhaustion model was subcutaneously administered once a week, respectively inducing 75-69-46 or 45-13-50 % of birth rates. In comparison, the similar mole of human menopausal gonadotropin (hMG) or human growth hormone (hGH) was administered once a day but caused just 25 or 20 % of birth rates. Grinodin induced more big ovarian follicles and corpora lutea than 2Y, hMG, hGH. The hMG-treated group was observed many distorted interstitial cells and more connective tissues and the hGH-treated group had few ovarian follicles. 2Y had a plasma lifetime of 21 days and higher GH release in mice, inducing lower birth rate and stronger individual specificity in reproduction as well as only promoting the proliferation of mesenchymal-stem-cells (MSCs) in the models. In comparison, Grinodin had a plasma lifetime of 30 days and much lower GH release in mice. It significantly promoted the proliferation and activation of ovarian MSCs together with the development of follicles in the models by increasing Ki67 and GHS-R expressions, and decreasing GHRH-R expression in a dose-dependent manner. However, the high GH and excessive estrogen levels in the models showed a dose-dependent reduction in fertility. Therefore, unlike 2Y, the low dose of Grinodin specifically shows low GHS-R and high GHRH-R expressions thus evades GH and estrogen release and improves functions of organs, resulting in an increase of fertility.

Linc00673-V3 positively regulates autophagy by promoting Smad3-mediated LC3B transcription in NSCLC.

Since its first discovery, long noncoding RNA Linc00673 has been linked to carcinogenesis and metastasis of various human cancers. Linc00673 had five transcriptional isoforms and their biological functions remained to be explored. Here we have reported that Linc00673-V3, one of the isoforms of Linc00673, promoted non-small cell lung cancer chemoresistance, and increased Linc00673-V3 expression level was associated with enhanced autophagy. Mechanistically, we discerned the existence of a stem-loop configuration engendered by the 1-100-nt and 2200-2275-nt fragments within Linc00673-V3. This structure inherently interacted with Smad3, thereby impeding its ubiquitination and subsequent degradation orchestrated by E3 ligase STUB1. The accumulation of Smad3 contributed to autophagy via up-regulation of LC3B transcription and ultimately conferred chemoresistance in NSCLC. Our results revealed a novel transcriptional regulation network between Linc00673-V3, Smad3, and LC3B, which provided an important insight into the interplay between autophagy regulation and non-canonical function of Smad3. Furthermore, the results from in vivo experiments suggested Linc00673-V3 targeted antisense oligonucleotide as a promising therapeutic strategy to overcome chemotherapy resistance in NSCLC.

Morphological and molecular analyses reveal two new species of Grifola (Polyporales) from Yunnan, China.

Species of Grifola are famous edible mushrooms and are deeply loved by consumers around the world. Most species of this genus have been described and recorded in Oceania, Europe and South America, with only Grifolafrondosa being recorded in Asia. In this study, two novel species of Grifola from southwestern China (Asia) are introduced. Macro and micromorphological characters are described. Grifolaedulissp. nov. present medium-size basidiomata with gray to gray-brown lobes upper surface, mostly tibiiform or narrowly clavate, rarely narrowly lageniform or ellipsoid chlamydospores, cuticle hyphae terminal segments slightly enlarged. Grifolasinensissp. nov. has white to grayish white lobes upper surface, mostly ellipsoid, rarely narrowly utriform chlamydospores, and broadly ellipsoid to ellipsoid basidiospores (4.6-7.9 × 3.0-5.9 µm). The two new species are supported by phylogenetic analyses of combined nuclear rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS) and ß-tubulin (TUBB). Moreover, the genetic distance between TUBB sequences of those specimen from GenBank was 1.76-1.9%. Thus, the conspecificity relationship of our specimens remains uncertain, and further specimens are required to conclusively confirm its identity.

Identification and oxidation of chlorinated paraffins containing nitrate esters, aliphatic sulfates, and thioether amino acids in sewage sludges.

Owing to the extensive production and widespread use of chlorinated paraffins (CPs), various CP structural analogs (CPSAs) have been detected in the environment, and these hydrophobic pollutants preferentially adsorb onto sludge during treatment. However, the species and sources of CPSAs in sludge and their subsequent fate during sludge oxidation treatments remain unclear. In this study, 320 nitrogen- or sulfur-containing CPs (205 CPs-N and 115 CPs-S) were detected in sludge through an analysis of Ph4PCl-enhanced ionization coupled with ultra-performance liquid chromatography (UPLC)-orbitrap-mass spectrometry (MS). The intensities of the newly found CPSAs were approximately 3.9-4.1 times those of CPs. Among these CPSAs, 273 previously unknown compounds, namely, 184 CPs-NO3, 63 CPs-SO4H, and 26 CPs-SH, were identified based on the characteristic fragments of NO3, SO4H, and SH, respectively. MS/MS analysis showed that the identified CPs-NO3 included 74 CPs-NO3, 71 CPs-NO3-NH2, 23 CPs-NO3-OH, and 16 CPs-NO3-NH2-OH; CPs-SO4H included 40 CPs-SO4H and 23 CPs-SO4H-OH; and CPs-SH could be divided into 19 2-(methylthio)acetamide-, 6 2-(methylthio)acetamide-cysteine-, and 1 N-acetylcysteine- containing CPs. High abundances of CPs-NO3 and CPs-SO4H were found in both sludge and CP commercial mixtures, indicating that these CPSAs likely originated from the production or use of industrial products. CPs-SH, which were present only in the sludge, were potentially derived from the biotransformation of CPs with amino acids. The oxidation of sludge resulted in the removal of 20.4-60.7 % of the newly identified CPSAs. The oxidation of CPs-NO3 and CPs-SO4H involved both carbon chain decomposition and hydroxylation processes, whereas CPs-SH underwent oxidation through carbon chain decomposition.

Efficacy of various surgical approaches in treating hematospermia using transurethral seminal vesiculoscopy.

PURPOSE: To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. MATERIALS AND METHODS: A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. RESULTS: The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). CONCLUSIONS: The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

PINK1-PTEN axis promotes metastasis and chemoresistance in ovarian cancer via non-canonical pathway.

BACKGROUND: Ovarian cancer is commonly associated with a poor prognosis due to metastasis and chemoresistance. PINK1 (PTEN-induced kinase 1) is a serine/threonine kinase that plays a crucial part in regulating various physiological and pathophysiological processes in cancer cells. METHODS: The ATdb database and "CuratedOvarianData" were used to evaluate the effect of kinases on ovarian cancer survival. The gene expression in ovarian cancer cells was detected by Western blot and quantitative real-time PCR. The effects of gene knockdown or overexpression in vitro were evaluated by wound healing assay, cell transwell assay, immunofluorescence staining, immunohistochemistry, and flow cytometry analysis. Mass spectrometry analysis, protein structure analysis, co-immunoprecipitation assay, nuclear-cytoplasmic separation, and in vitro kinase assay were applied to demonstrate the PINK1-PTEN (phosphatase and tensin homolog) interaction and the effect of this interaction. The metastasis experiments for ovarian cancer xenografts were performed in female BALB/c nude mice. RESULTS: PINK1 was strongly associated with a poor prognosis in ovarian cancer patients and promoted metastasis and chemoresistance in ovarian cancer cells. Although the canonical PINK1/PRKN (parkin RBR E3 ubiquitin protein ligase) pathway showed weak effects in ovarian cancer, PINK1 was identified to interact with PTEN and phosphorylate it at Serine179. Remarkably, the phosphorylation of PTEN resulted in the inactivation of the phosphatase activity, leading to an increase in AKT (AKT serine/threonine kinase) activity. Moreover, PINK1-mediated phosphorylation of PTEN impaired the nuclear import of PTEN, thereby enhancing the cancer cells' ability to resist chemotherapy and metastasize. CONCLUSIONS: PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. PINK1 promotes ovarian cancer metastasis and chemotherapy resistance through the regulation of PTEN. These findings offer new potential therapeutic targets for ovarian cancer management.

Juvenile Nasopharyngeal Angiofibroma in Postmenopausal Females: A Potential Link With Hyperandrogenism.

A 54-year-old female presented to the otolaryngology (ENT) outpatient department with an eight-month history of unilateral nasal obstruction and headache. There was no change in the sense of smell, rhinorrhoea, facial pain, or associated epistaxis. On examination, there was a large, erythematous mass in the superior aspect of the right nasal cavity, filling the space between the nasal septum, middle, and superior meatus. The rest of the ENT examination was normal. Vital signs were all within the normal range. There was no significant past medical history, and she had tried steroid nasal spray without any benefit. She had a complete resolution of symptoms from surgical intervention, and the mass was confirmed to be an angiofibroma through histopathology. This case report discusses the importance of considering nasopharyngeal angiofibroma as a differential diagnosis for patients presenting with unilateral nasal masses, including female patients, regardless of age.

Poorly cohesive duodenal carcinoma mixed with signet ring cell carcinoma with systemic metastasis: a case report and literature review.

Poorly cohesive duodenal carcinoma mixed with signet ring cell carcinoma is very rare, and no cases have been reported. When distant metastasis occurs, it is very easy to be misdiagnosed. We report the first case of a 52-year-old man with poorly cohesive carcinoma of the duodenum mixed with signet ring cell carcinoma with systemic metastasis. The process of its diagnosis and differential diagnosis is highlighted.

Control status of ambulatory blood pressure and its relationship with arterial stiffness in the China nationwide registry of treated hypertensive patients: the REACTION-ABP study.

The control rate of ambulatory blood pressure (BP) is unclear in Chinese hypertensive patients, and whether it would be associated with the ambulatory arterial stiffness indices is also unknown. From June 2018 until December 2022, 4408 treated hypertensive patients (52.8% men, average age 58.2 years) from 77 hospitals in China were registered. Ambulatory BPs were measured with validated monitors and analyzed with a web-based standardized Shuoyun system ( www.shuoyun.com.cn ). The BP control rate was the highest in the office (65.7%), moderate in the daytime (45.0%), low in the morning (34.1%), and the lowest in the nighttime (27.6%, P < 0.001). Only 21.0% had their 24 h BP perfectly controlled. The stepwise regression analyses identified that the factors associated with an imperfect 24 h BP control included male sex, smoking and drinking habits, a higher body mass index, serum total cholesterol and triglycerides, and the use of several specific types of antihypertensive drugs. After adjustment for the above-mentioned factors, the 24 h pulse pressure (PP) and its components, the elastic and stiffening PPs, were all significantly associated with an uncontrolled office and ambulatory BP status with the standardized odds ratios ranging from 1.09 to 4.68 (P < 0.05). The ambulatory arterial stiffness index (AASI) was only associated with an uncontrolled nighttime and 24 h BP status. In conclusion, the control rates of 24 h ambulatory BP, especially that in the nighttime and morning time windows, were low in Chinese hypertensive patients, which might be associated with arterial stiffness in addition to other common risk factors.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.

Peritoneal metastasis is a key feature of advanced ovarian cancer, but the critical protein required for ovarian cancer metastasis and progression is yet to be defined. Thus, an unbiased high throughput and in-depth study is warranted to unmask the mechanism. Transcriptomic sequencing of paired primary ovarian tumors and metastases unveiled that MAP4K4, a serine/threonine kinase belongs to the Ste20 family of kinases, was highly expressed in metastatic sites. Increased MAP4K4 expression in metastasis was further validated in other independent patients, with higher MAP4K4 expression associated with poorer survival, higher level of CA125 and more advanced FIGO stage. Down regulation of MAP4K4 inhibited cancer cell adhesion, migration, and invasion. Notably, MAP4K4 was found to stabilize N-cadherin. Further results showed that MAP4K4 mediated phosphorylation of ADAM10 at Ser436 results in suppression of N-cadherin cleavage by ADAM10, leading to N-cadherin stabilization. Pharmacologic inhibition of MAP4K4 abrogated peritoneal metastases. Overall, our data reveal MAP4K4 as a significant promoter in ovarian cancer metastasis. Targeting MAP4K4 may be a potential therapeutic approach for ovarian cancer patients.

Influencing Mechanism of Titanium-Extracted Tailing Slag on the Strength of CaO Steel Slag Hardened Paste.

Hardened pastes with different mass percentages of steel slag (SS)/titanium-extracted tailing slag (TETS) were prepared under fixed CaO content to determine the influencing mechanism of TETS on the strength of CaO SS hardened paste. Furthermore, the effects and laws of curing time and SS/TETS ratios on the strength of hardened pastes were also investigated in this study. Importantly, hydration products, microstructures and the micro-area compositions of hardened pastes were analysed using X-ray diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy-energy dispersive spectrometer, respectively, to reveal the influencing mechanism of TETS on the CaO SS hardened pastes. The results demonstrated that the early strength of hardened pastes increases considerably following the inclusion of TETS. Specifically, the strength of the sample with an SS/TETS ratio of 22.5:67.5 at 1 d can be increased by more than 14 times. Notably, its strength at 90 days reached 19.36 MPa. Moreover, the diffraction peaks of calcite and C-S-H in the samples were also strengthened. Meanwhile, a diffraction peak of hydrocalumite appeared, and the calcites in the samples were curled up. When the SS/TETS ratio was equal to or more than 45:45, a diffraction peak of Ca(OH)2 appeared in the sample. Only a diffraction peak of Ca(OH)2 and weak diffraction peaks of calcite and C-S-H were observed in the samples without TETS, but there was no diffraction peak of hydrocalumite. The strength at 90 days was only 4.92 MPa. The increased strength of the hardened paste is closely related to the production of new phases after adding TETS. Solid particles in the hardened paste are cemented into a whole because of the hydration of C-S-H. Calcite forms the skeleton of the hardened pastes, whereas hydrocalumite fills in the pores among particles in hardened pastes, thus making them more compacted. As a result, there is increased.

Association between Different Types of Tea Consumption and Risk of Gynecologic Cancer: A Meta-Analysis of Cohort Studies.

Plenty of studies have shown that tea has an effect of inhibiting gynecologic tumors. However, there still remained controversy of the association between tea and gynecologic tumors in epidemiological studies. In this study, PubMed, Embase, and Cochrane Database were used to search the literature from 1 January 1960 to 26 December 2022 to investigate the association between tea intake and gynecologic cancer risk. In total, 19 cohort studies with 2,020,980 subjects and 12,155 gynecological tumor cases were retrieved. The pooled relative risk (RR) of gynecologic tumor for tea intake was 1.00 (95% CI: 0.96-1.04). RRs were 0.94 (95% CI: 0.88-1.01) for ovarian cancer, 1.02 (95% CI: 0.97-1.07) for endometrial cancer, and 1.06 (95% CI: 0.91-1.23) for cervical cancer. Subgroup analyses were adopted based on the tea type and geographic location. Interestingly, significant preventive impact of non-herbal tea on ovarian cancer (pooled relative risk: 0.67; 95% CI: 0.55-0.81) was found, especially for black tea (pooled relative risk: 0.64; 95% CI: 0.51-0.80). Dose-response analysis indicated that although it is not statistically significant, a decreasing trend of ovarian cancer risk could be observed when the tea consumption was 1.40 to 3.12 cups/day. In conclusion, our findings suggested that ovarian cancer, but not other gynecologic cancers, could possibly be prevented by drinking non-herbal tea. In addition, the preventive impact of green tea on gynecologic cancer seemed to be relatively weak and needs further cohorts to validate it.

Trends in elemental Pb concentrations within atmospheric PM2.5 and associated risk to human health in major cities of China.

High concentrations of elemental lead (Pb) in the atmosphere pose a serious threat to human health. This study presents and summarizes data obtained from relevant literature on Pb concentrations within fine particulate matter (PM2.5) recorded in major cities in China from 2008 to 2019. An environmental health risk assessment model was then used to evaluate the health hazards of inhaling Pb among adults and children in China. Owing to the promulgation and implementation of a series of air pollution control measures, the Pb concentrations within PM2.5 measured in major cities in China showed a downward trend after peaking in 2013. The concentrations were higher in winter than in summer, and higher in northern cities than in southern cities. Although the Pb concentrations in most cities did not exceed the limit (500 ng/m3) set by China, they remained much higher than concentrations recorded in developed countries. The results of the environmental health risk analysis showed that the non-carcinogenic risk from atmospheric Pb exposure was higher in children than in adults (adult females > adult males), while the carcinogenic risk was higher in adults than in children. This study shows that even if the health risk of Pb in PM2.5 does not exceed the acceptable limit, stricter Pb pollution control measures are required to safeguard population health due to the dangers of Pb.

Enhancing ethylene glycol and ferric chloride pretreatment of rice straw by low-pressure carbon dioxide to improve enzymatic saccharification.

Ethylene glycol and ferric chloride pretreatment assisted by low-pressure carbon dioxide (1 MPa CO2) realized the targeted deconstruction of lignocelluloses at 170 °C for 5 min, achieving 98 % cellulose recovery with removal of 92 % lignin and 90 % hemicellulose. After the pretreatment, the formation of stable platform mono-phenol components would be with the destruction of the lignin-carbohydrate complexes structure, and the surface of rice straw became rough, with a less negative charge and higher specific surface area, while the enzyme adsorption rate increased by 8.1 times. Furthermore, the glucose yield of pretreated straw was remarkably increased by 5.6 times that of the untreated straw, reaching 91 % after hydrolyzed for 48 h. With Tween 80 added in concentrated solid (12 %) hydrolysis at low cellulase loading (3 FPU/g dry substrate), half of the hydrolysis time was shortened than that without Tween 80, with 45 % higher glucose yield.

Positive outcomes with neoadjuvant chemotherapy in the management of colovesical fistula in cancer: a case report and literature review.

Colovesical fistula (CVF) is usually developed from colonic diverticulitis, followed by tumor. Traditional surgery is usually completed in one or more stages. For complex cancerous CVF, radical resection is more difficult. We report a 62-year-old male patient diagnosed with sigmoid colon cancer combined with sigmoid vesical fistula. In the course of treatment, in addition to conventional surgery, neoadjuvant chemotherapy (NAC) was innovatively used. The sigmoid tumor and fistula were significantly shrunken. Radical surgery achieved negative margins.

Species diversity of Ganoderma (Ganodermataceae, Polyporales) with three new species and a key to Ganoderma in Yunnan Province, China.

Ganoderma is a globally distributed genus that encompasses species with forestry ecological, medicinal, economic, and cultural importance. Despite the importance of this fungus, the studies on the species diversity of Ganoderma in Yunnan Province, China (YPC) have poorly been carried out. During this study, opportunistic sampling was used to collect 21 specimens of Ganoderma from YPC. Morphology and multigene phylogeny of the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nrLSU), the translation elongation factor 1-α gene (TEF1-α), and the second largest subunit of RNA polymerase II (RPB2) were used to identify them. Morphological and molecular characterization of the 21 specimens showed that they belong to 18 species of Ganoderma, of which three are novel viz. G. artocarpicola, G. obscuratum and G. yunnanense. Ganoderma artocarpicola is characterized by the sessile and concrescent basidiomata, reddish brown to yellowish brown pileus surface, heterogeneous context, wavy margin, and ovoid basidiospores. Ganoderma obscuratum is distinguished by small pores (6-9 per mm), dorsolaterally sub-stipitate basidiomata which become greyish-brown when dry, and narrow ellipsoid basidiospores. Ganoderma yunnanense is characterized by cream color pore surface and context, centrally to laterally stipitate basidiomata with reddish-brown to violet-brown strongly laccate pileus surface, and broadly ellipsoid basidiospores. With the help of an extensive literature survey and the results of this study, a checklist of 32 Ganoderma species from YPC was established, which accounts for 71.11% of the known species in China. In addition, a key to the Ganoderma in YPC is also provided.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway.

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-ß production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.