Search

Cadmium (Cd) is a toxic heavy metal with a high propensity to accumulate within the body, and Cd accumulation has been shown to cause organ damage. However, it is unclear whether Cd accumulation is a cause of impaired decidualization, which induces to spontaneous abortion (SA). In this study, we found that the decidual Cd concentration was increased in patients with SA and positively correlated with the occurrence of SA. The levels of two decidualization markers (prolactin, PRL and insulin-like growth factor binding protein 1, IGFBP1) were reduced in the decidua of all-cause SA patients. Using 8-week ICR female mice, we further established a uterus-specific Cd accumulation mouse model and verified that Cd-accumulating mice had increased numbers of absorbed fetuses and defective decidualization. Finally, using in vitro-cultured human ENdometrial stromal cells (hEnSCs), we found that Cd accumulation significantly inhibited decidualization; and moreover, Cd treatment downregulated the regulatory genes upstream of PRL and IGFBP1 such as PGR, ESR1, ESR2 and FOXO1. This study suggests that Cd accumulation could produce impaired decidualization by downregulating the upstream regulators of PRL and IGFBP1, thereby increasing the risk of SA. Our study offered new possibilities for the prevention and treatment of spontaneous abortion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Locally advanced cervical carcinoma (LACC) remains a significant global health challenge owing to its high recurrence rates and poor outcomes, despite current treatments. This study aimed to develop a comprehensive risk stratification model for LACC by integrating Cox regression and competing risk analyses. This was done to improve clinical decision making. We analyzed data from 3428 patients with LACC registered in the Surveillance, Epidemiology, and End Results program and diagnosed them between 2010 and 2015. Cox regression and competing risk analyses were used to identify the prognostic factors. We constructed and validated nomograms for overall survival (OS) and disease-specific survival (DSS). Multivariate Cox regression identified key prognostic factors for OS, including advanced International Federation of Gynecology and Obstetrics stage, age, marital status, ethnicity, and tumor size. Notably, International Federation of Gynecology and Obstetrics stages IIIA, IIIB, and IVA had hazard ratios of 2.227, 2.451, and 4.852, respectively, significantly increasing the mortality risk compared to stage IB2. Ethnic disparities were evident, with African Americans facing a 39.8% higher risk than Caucasians did. Competing risk analyses confirmed the significance of these factors in DSS, particularly tumor size. Our nomogram demonstrated high predictive accuracy, with area under the curve values ranging from 0.706 to 0.784 for DSS and 0.717 to 0.781 for OS. Calibration plots and decision curve analyses further validated the clinical utility of this nomogram. We present effective nomograms for LACC risk stratification that incorporate multiple prognostic factors. These models provide a refined approach for individualized patient management and have the potential to significantly enhance therapeutic strategies for LACC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with concurrent acute myeloid leukemia (AML) and active pulmonary tuberculosis (TB) exhibit certain characteristics; cough, phlegm, fever, hemoptysis, weight loss and dyspnea are common symptoms of both diseases. These patients often cannot tolerate traditional intensive chemotherapy regimens, and finding the optimal timing in the treatment of both AML and active pulmonary TB is complex. Neglecting timely treatment can lead to serious complications and even fatal outcomes. The present paper reports two cases of patients with AML who were diagnosed with active pulmonary TB. The patients received intensive anti-TB treatment with isoniazid, rifampicin, pyrazinamide and ethambutol for 10-15 days. After three consecutive negative sputum smears, the patients in cases 1 and 2 were treated with a venetoclax, homoharringtonine and cytarabine regimen; and a venetoclax and azacitidine regimen for anti-AML therapy, respectively, as well as individualized anti-TB regimens of isoniazid, pyrazinamide, ethambutol and quinolone. Subsequently, both patients achieved complete remission of AML and their active TB was well controlled., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Ji et al.)

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs.  1-5 ), yet the experimental realization is hard to achieve 6,7 . The recently discovered vanadium-based kagome materials 8 , which exhibit both superconductivity 9-11 and charge-density-wave orders 12-14 , are nonmagnetic 8,9 and weakly correlated 15,16 . Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr 3 Sb 5 , which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a 0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, T c max  = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors 17,18 . Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030., Methods: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index., Results: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019., Conclusions: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions., (© 2024. The Author(s).)

Background: Growing evidence suggests that headache disorders and atopic dermatitis share similar pathological mechanisms and risk factors. The aim of this study was to assess the risk for headache disorders in patients with atopic dermatitis., Methods: We systematically searched the PubMed and Embase databases from inception to December 1, 2023, for observational studies that examined risk of migraine in subjects with atopic dermatitis. Risk estimates from individual studies were pooled using random-effects models., Results: Ten studies with 12,717,747 subjects were included in the meta-analysis. Our results showed that patients with atopic dermatitis were associated with a higher risk of headache disorder (OR, 1.46, 95% CI = 1.36-1.56; P < 0.001; I 2  = 98%) or migraine (OR, 1.32, 95% CI = 1.18-1.47; P < 0.001; I 2  = 98.9%). Most of the results of the subgroup analyses were consistent with the overall results., Conclusion: The findings of this meta-analysis suggest that atopic dermatitis is a potential risk indicator for headache disorder or migraine. Further studies are still needed to verify our findings due to the substantial heterogeneity in our analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Dai, Xu, Jiang and Ding.)

Normally, only noncentrosymmetric structure of the materials can potentially be piezoelectric. Thus, it is limited in the field of piezoelectricity for the centrosymmetric structure of the material. In this work, the performance of piezoelectricity is successfully achieved from centrosymmetric SrFeO 3- x by modulating oxygen vacancies, which have a surface piezoelectric potential up to 93 mV by using Kelvin-probe force microscopy (KPFM). Moreover, the piezoelectric effects of SrFeO 3- x are also evaluated by piezoelectric catalytic effect and density functional theory calculations (DFT). The results show that the piezo-catalytic degradation of tetracycline reaches 96% after 75 min by ultrasonic mechanical vibration and the production of H 2 O 2 by SrFeO 3- x piezoelectric synthesis could reach 1821 µmol L -1 . In addition, the DFT results indicate that the intrinsic effect of oxygen vacancies effectively promotes the adsorption and activation of O 2 and H 2 O as well as intermediates and improves the piezoelectric catalytic activity. This work provides an effective basis for realizing the piezoelectricity of centrosymmetric materials and regulating the development of piezoelectric catalytic properties., (© 2023 Wiley‐VCH GmbH.)

Cadmium (Cd), an environmental contaminant, can result in placental non-selective autophagy activation and fetal growth restriction (FGR). However, the role of placental lipophagy, a selective autophagy, in Cd-induced FGR is unclear. This work uses case-control study, animal experiments and cultures of primary human placental trophoblast cells to explore the role of placental lipophagy in Cd-induced FGR. We found association of placental lipophagy and all-cause FGR. Meanwhile, pregnancy Cd exposure induced FGR and placental lipophgay. Inhibition of placental lipophagy by pharmacological and genetic means (Atg5 -/- mice) exacerbated Cd-caused FGR. Inversely, activating of placental lipophagy relieved Cd-stimulated FGR. Subsequently, we found that activation of Atg5-dependent lipophagy degrades lipid droplets to produce free cholesterol, and promotes placental progesterone (P4) synthesis. Gestational P4 supplementation significantly reversed Cd-induced FGR. Altogether, activation of Atg5-dependent placental lipophagy ameliorates Cd-induced FGR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In March 2022, a 58-year-old man was admitted to the local hospital for nausea and vomiting. His blood routine indicated that he had leukocytosis and anemia. The patient was diagnosed with acute myeloid leukemia (AML)-M5b accompanied by DNMT3A, FLT3-TKD , and IDH2 mutations, chest CT revealed pulmonary tuberculosis (TB). Acid-fast bacillus (AFB) was detected in sputum. The patient then received anti-TB treatment with isoniazid + rifampicin + pyrazinamide + ethambutol. On April 8, he was transferred to our hospital's Hematology Department after three consecutive negative sputum smears. He was administered the VA (Venetoclax + Azacytidine) regimen of anti-leukemia treatment and also received levofloxacin + isohydrazide + pyrazinamide + ethambutol anti-TB treatment. After one course of VA therapy, there was no remission in the bone marrow. Therefore, the patient received the HVA (Homeharringtonine + Venetoclax + Azacytidine) regimen of anti-leukemia treatment. On May 25, the bone marrow smear revealed that the original mononuclear cells were 1%. Moreover, bone marrow flow cytometry revealed the absence of any abnormal cells. mNGS showed DNMT3A (mutation rate 44.7%), but no mutations were detected in FLT3-TKD and IDH2. The patient then received the HVA regimen three consecutive times, resulting in complete remission. Repeated chest CT examinations revealed progressive regression of pulmonary TB foci, no AFB was detected in the sputum. This AML patient with DNMT3A, FLT3-TKD, and IDH2 mutations and active TB is difficult to treat. It is very necessary for him to administer prompt anti-leukemia treatment under the premise of active anti-TB treatment. The HVA regimen is effective for this patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ji, Yang, Xu and Xu.)

A 49-year-old woman with a rare autoimmune hematological disease, Evans syndrome, was admitted to the authors' hospital with immune reconstitution inflammatory syndrome-like reconstitution syndrome after effective antifungal therapy for cryptococcal meningitis. She initially improved after receiving corticosteroid treatment; after prednisone was tapered, her clinical presentation and brain imaging deteriorated but finally improved with the addition of thalidomide. Immune reconstitution inflammatory syndrome-like reconstitution syndrome is a rare complication in cryptococcal meningitis patients receiving immunosuppressive therapy. Thalidomide can be given in addition to corticosteroid therapy to effectively control the paradoxical inflammatory response and improve clinical outcomes.

Traditional SrTiO 3 (STO) materials have high brittleness and poor deformation resistance. In this work, macroscopically flexible iron-doped SrTiO 3 (SFTO) nanofibrous membranes were prepared by electrospinning and calcination, which can be easily isolated and can maintain integrity to recycle as photocatalysts. Moreover, the SFTO nanofibrous membranes showed enhanced photocatalytic performance under strong acids (pH = 2) and strong alkalis (pH = 12). The SFTO nanofibrous membranes increased the catalytic rate of Congo red (CR) dye by about 10 times in visible light. The mechanism of photocatalytic activity enhancement was discussed by the combined effects of hydroxyl radicals and superoxide radicals. The successful preparation of SFTO nanofibrous membranes has offered a simple and economical approach to photocatalysis as well as environmental remediation.

Acquiring adsorbents capable of effective radioiodine capture is important for nuclear waste treatment; however, it remains a challenge to develop porous materials with high and reversible iodine capture. Herein, we report a porous self-assembly constructed by a cup-shaped Pd II complex through intermolecular π ··· π interactions. This self-assembly features a cubic structure with channels along all three Cartesian coordinates, which enables it to efficiently capture iodine with an adsorption capacity of 0.60 g g -1 for dissolved iodine and 1.81 g g -1 for iodine vapor. Furthermore, the iodine adsorbed within the channels can be readily released upon immersing the bound solid in CH 2 Cl 2 , which allows the recycling of the adsorbent. This work develops a new porous molecular material promising for practical iodine adsorption.

Objective: To construct and verify a key gene signature of the basement membrane of prostate cancer (PCa) to predict the progression and biochemical recurrence of the malignancy after radical prostatectomy., Methods: Based on the PCa-related transcriptome, gene mutation and clinical data from the Cancer Genome Atlas Project (TCGA) database, we analyzed the differentially expressed genes (DEG) related to the basement membrane in the PCa and adjacent normal prostate tissues, and subjected them to GO function enrichment and KEGG pathway enrichment analyses. We identified prognosis-related genes from the DEGs and analyzed their mutations. According to the follow-up data and biochemical recurrence after prostatectomy, we established a prognostic risk scoring model, verified its accuracy using the Gene Expression Omnibus (GEO) database, and performed survival analysis, principal component analysis (PCA), independent prognostic analysis and ROC curve analysis of the model. We constructed a protein-protein interaction network after verifying the correctness of the model by immunohistochemistry. We also established a nomogram and tested its accuracy using ROC and calibration curves., Results: Totally, 85 DEGs were identified, among which 18 were up-regulated and 67 down-regulated. The prognostic risk scoring model was established with 11 of the genes. The risk of biochemical recurrence PCa was significantly higher in the high-risk than in the low-risk group (HR: 3.51, 95% CI: 2.32－5.32, P < 0.01), which was verified with the GEO database data (P < 0.01). In addition, the patients in the high-risk group were older with higher clinical T-stage, higher Gleason score, higher positive rate, larger numbers of positive lymph nodes, and a larger proportion of residual tumors than those in the low-risk group (P < 0.05). The nomogram constructed with the patients' age, pN, pT and cT stages, Gleason score and prognostic risk score manifested that the area under the ROC curve was higher than the other predictors. The calibration chart showed consistency of the predicted outcomes to the actual results., Conclusion: A prognostic risk scoring model of basement membrane-related genes and an effective nomogram were successfully constructed, which can predict the risk of biochemical recurrence in PCa patients after radical prostatectomy.

Objective: To discuss the clinical diagnosis and treatment of extragonadal germ cell tumor., Methods: We analyzed the clinical data on a case of extragonadal germ cell tumor diagnosed and treated in the General Hospital of Eastern Theater Command and reviewed the relevant literature., Results: The patient was initially diagnosed with retroperitoneal tumor and treated by resection of the tumor together with the left kidney due to the large volume of the tumor, which was complicated by pancreatic injury. Postoperative pathology showed it to be extragonadal germ cell malignancy. Postoperative examination revealed space-occupying lesion in the left testis, with serum alpha fetoprotein (AFP), human chorionicgonadotropin (hCG) and lactate dehydrogenase (LDH) negative, followed by stage-two resection of the left testis, which was pathologically shown with testicular seminoma. The patient received 7 courses of cisplatin, etoposide bleomycin (PEB) regimen and was followed up for 8 years, which found no recurrence or metastasis, and the patient fathered no child during the postoperative follow-up., Conclusion: For patients with a history of cryptorchidism and tumors located in the central axis, special attention should be paid to physical examination of the testes, testicular ultrasonography, and determination of AFP and other indicators to identify gonadal tumor metastasis. And if so, radiotherapy and chemotherapy can be considered first to reduce surgical complications and achieve accurate management.

To explore the brain volume (BV) changes of HIV-negative and non-transplant cryptococcal meningitis (CM) in 1 year after initial therapy. Case data were collected from 78 CM patients who underwent magnetic resonance imaging (MRI) scanning at least 3 times in 1-year interval after initial therapy. The assessment of BV was measured by a non-commercial software, uAI Research Portal. Linear mixed model was used to investigate the association between clinical characteristics and the changes in BV. Longitudinal study showed a decrease in total brain volume (-4.65 cm3, P = .005), regional brain volume including white matter (-2.86 cm3, P = .031) and basal ganglia (-0.25 cm3, P = .007), and increase in cerebrospinal fluid (CSF) volume (3.58 cm3, P = .013) in CM patients in 1 year after initial therapy. Ventricular volume in patients with ventriculoperitoneal shunts (VPS) was lower than that in patients without VPS (-7.5 cm3, P < .05). Ventricular volume in patients with post-infectious inflammatory response syndrome (PIIRS) was larger than that in patients without PIIRS (7.1 cm3, P < .01). In addition, temporal lobe atrophy was associated with corticosteroid therapy (-6.8 cm3, P < .01). The present study suggested that brain atrophy, especially regional BV decrease, could happen in HIV-negative and non-transplant CM patients over a 1-year interval., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Objectives: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM)., Methods: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China., Results: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035)., Conclusions: This study demonstrated that species identification helps to guide therapy and predict outcomes., (© 2022 Wiley-VCH GmbH.)

The present study described the clinical presentation of patients with cesarean scar pregnancy type II (CSP)-II diagnosed by ultrasound or magnetic resonance imaging, who underwent laparoscopic surgery resection or hysteroscopic treatment. The aim of the present study was to evaluate the outcomes of different treatments for CSP. The patients with CSP-II were assigned to the laparoscopy and hysteroscopy groups according to the type of surgery performed. The general indicators and post-operative outcomes were compared between the two groups. Statistically significant differences (P<0.05) were noted in the treatment efficacy indices between the two groups. The laparoscopic group exhibited a lower value of β-human chorionic gonadotropin (β-HCG) following surgery (P = 0.017), a shorter time required for β-HCG to return to normal levels (P = 0.001), a reduced post-operative thickness of the uterine scar (P<0.001) and a reduced menstruation recovery time (P<0.001). However, no significant differences were noted in blood loss during operation (P>0.05). On the whole, the data indicated that the laparoscopic resection of the scar with gestational tissue and wound repair may be used to preserve the uterus and may thus be an effective method for CSP-II. The appropriate treatment needs to be selected according to the condition of each patient. Based on the latter and on the available technology, priority may perhaps be given to laparoscopic surgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Man Li et al.)

In Escherichia coli, transcription-translation coupling is mediated by NusG. Although chloroplasts are descendants of endosymbiotic prokaryotes, the mechanism underlying this coupling in chloroplasts remains unclear. Here, we report transcription-translation coupling through AtNusG in chloroplasts. AtNusG is localized in chloroplast nucleoids and is closely associated with the chloroplast PEP complex by interacting with its essential component PAP9. It also comigrates with chloroplast ribosomes and interacts with their two components PRPS5 (uS5c) and PRPS10 (uS10c). These data suggest that the transcription and translation machineries are coupled in chloroplasts. In the atnusg mutant, the accumulation of chloroplast-encoded photosynthetic gene transcripts, such as psbA, psbB, psbC and psbD, was not obviously changed, but that of their proteins was clearly decreased. Chloroplast polysomic analysis indicated that the decrease in these proteins was due to the reduced efficiency of their translation in this mutant, leading to reduced photosynthetic efficiency and enhanced sensitivity to cold stress. These data indicate that AtNusG-mediated coupling between transcription and translation in chloroplasts ensures the rapid establishment of photosynthetic capacity for plant growth and the response to environmental changes. Therefore, our study reveals a conserved mechanism of transcription-translation coupling between chloroplasts and E. coli, which perhaps represents a regulatory mechanism of chloroplast gene expression. This study provides insights into the underlying mechanisms of chloroplast gene expression in higher plants., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To evaluate effectiveness of self-designed adjustable cannulated screw guide, and to provide an effective auxiliary tool for inverted triangular arrangement of compression cannulated screws in clinical treatment for transcervical femoral neck fractures., Methods: The sketch of instrument was drawn with Solidworks software, and physical product was obtained after production. The data were obtained by Mimics software. Combined with the guide, it was first used on 22 cadaveric bones, 22 dry cadaveric bones, including 12 males and 10 females. Then the distribution of guide pins was evaluated by X-ray film. The anatomical size and screw distance of femoral head and neck were measured in different ways, and statistically compared. From January 2018 to June 2020, 45 hospitalized patients with femoral neck fracture were selected and divided into new guide group (22 patients) and free hand nail group (23 patients) according to whether the instrument was used or not. The clinical data and operation conditions between two groups were recorded and compared., Results: The anatomical data of X-ray, three-dimensional and physical measurement were basically the same, whlie had no difference ( P >0.05). There was no significant difference between physical measurement and three-dimensional measurement ( P >0.05). The distance between screws and needle entry point was designed as an isosceles triangle( r =0.992 8, P <0.000 1), but due to the existence of femoral anteversion and torsion angle, it was an approximate isosceles triangle in the femoral neck ( r =0.824 1, P <0.000 1). The patients between two groups were followed up for an average of 2 years. There was no significant difference in the number of fluoroscopy and puncture between new guide group and free hand nail group( P >0.05). The screw parallelism was better and operation time was shorter which had statistically difference( P <0.05). However, there was no significant difference in final Harris score and incidence of complications between two groups( P >0.05)., Conclusion: Self-made femoral neck cannulated screw guide combined with preoperative planning of Mimics software is conducive to placement of inverted triangular arrangement of cannulated screws, but it still needs to be improved and followed up in the later large-scale use.

AtRsmD was recently demonstrated to be a chloroplast 16S rRNA methyltransferase (MTase) for the m 2 G915 modification in Arabidopsis. Here, its function of AtRsmD for chloroplast development and photosynthesis was further analyzed. The AtRsmD gene is highly expressed in green photosynthetic tissues. AtRsmD is associated with the thylakoid in chloroplasts. The atrsmd-2 mutant exhibited impaired photosynthetic efficiency in emerging leaves under normal growth conditions. A few thylakoid lamellas could be observed in the chloroplast from the atrsmd-2 mutant, and these thylakoids were loosely organized. Knockout of the AtRsmD gene had minor effects on chloroplast ribosome biogenesis and RNA loading on chloroplast ribosomes, but it reduced the amounts of chloroplast-encoded photosynthesis-related proteins in the emerging leaves, for example, D1, D2, CP43, and CP47, which reduced the accumulation of the photosynthetic complex. Nevertheless, knockout of the AtRsmD gene did not cause a general reduction in chloroplast-encoded proteins in Arabidopsis grown under normal growth conditions. Additionally, the atrsmd-2 mutant exhibited more sensitivity to lincomycin, which specifically inhibits the elongation of nascent polypeptide chains. Cold stress exacerbated the effect on chloroplast ribosome biogenesis in the atrsmd-2 mutant. All these data suggest that the AtRsmD protein plays distinct regulatory roles in chloroplast translation, which is required for chloroplast development and chloroplast function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Qu, Mei, Zhang, Yang, Xu, Xiong, Yang and Yu.)

Photoperiod/temperature-sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms-2 (res3), as the male sterility of rvms-2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis., (© 2021 Institute of Botany, Chinese Academy of Sciences.)

Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Limited attention has been paid to abnormal blood and urine test results for patients with bladder cancer. The present study aimed to identify whether blood and urine parameters are associated with bladder cancer., Methods: We used a case-control design and matched each patient with bladder cancer with three healthy controls of the same age and sex. Univariate conditional logistic regression was used to calculate the crude and adjusted odds ratio (OR) and its 95% CI. Multivariate conditional logistic regression was performed for confounders adjustment, and Spearman's correlation coefficient was used to assess the correlation between tumor T stages and urine parameters., Results: Patients with bladder cancer (n = 360) and controls (n = 1050) were recruited. In the univariate conditional logistic analysis, higher urine pH was associated with a decreased risk of bladder cancer (OR = 0.67, 95% CI = 0.57-0.78), while higher values of urine protein (OR = 4.55, 95% CI = 3.36-6.15), urine glucose (OR = 1.56, 95% CI = 1.18-2.05), and urine occult blood (OR = 4.27, 95% CI = 3.44-5.29) were associated with an increased risk of bladder cancer. After adjustment for body mass index, fasting blood glucose, hypertension, red blood cells, white blood cells, lymphocytes, neutrophils, and platelets, significance still remained for urine pH (OR = 0.68, 95% CI = 0.53-0.88), urine protein (OR = 1.97, 95% CI = 1.21-3.19), urine glucose (OR = 2.61, 95% CI = 1.39-4.89), and urine occult blood (OR = 3.54, 95% CI = 2.73-4.58)., Conclusion: This study indicated that lower urine pH and higher values of urine protein, urine glucose, and urine occult blood might be risk factors for bladder cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Shuai, Zheng, Guo, Huang, Xu, Li, Zi, Ming, Ren and Zeng.)

Environmental cadmium (Cd) is positively associated with placental impairment and fetal growth retardation. Nevertheless, its potential mechanisms remain unclear. microRNAs (miRNAs) are known to influence placental development and fetal growth. This work was aimed to determine which miRNAs are involved in Cd-impaired placental and fetal development based on the mRNA and miRNA expression profiles analysis. As a result, gestational Cd exposure deceased fetal and placental weight, and reduced the protein level of PCNA in human and mouse placentae. Furthermore, the results of mRNA microarray showed that Cd-downregulated mRNAs were predictively correlated with several biological processes, including cell proliferation, differentiation and motility. In addition, the results of miRNA microarray and qPCR assay demonstrated that Cd significantly increased the level of miR-6769b-5p, miR-146b-5p and miR-452-5p. Integrated analysis of Cd-upregulated miRNAs predicted target genes and Cd-downregulated mRNAs found that overlapping mRNAs, such as CCND1, CDK13, RINT1 and CDC26 were also significantly associated with cell proliferation. Further experiments showed that miR-6769b-5p inhibitor, but not miR-146b-5p and miR-452-5p, markedly reversed Cd-downregulated the expression of proliferation-related mRNAs, and thereby restored Cd-decreased the proteins level of CCND1 and PCNA in human placental trophoblasts. Dual luciferase reporter assay further revealed that miR-6769b-5p directly targets CCND1. Finally, the case-control study demonstrated that increased miR-6769b-5p level and impaired cell proliferation were observed in small-for-gestational-age human placentae. In conclusion, miR-6769b-5p targets CCND-1 to regulate proliferation in Cd-treated placental trophoblasts, which is associated with the impairment of fetal growth. Our findings imply that placental miR-6769b-5p may be used as an epigenetic marker for environmental pollutants-caused fetal growth restriction and its late-onset chronic diseases., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The burden of kidney, bladder, and prostate cancers has changed in recent decades. This study aims to investigate the global and regional burden of, and attributable risk factors for genitourinary cancers during the past 30 years., Methods: We extracted data of kidney, bladder, and prostate cancers from the Global Burden of Disease 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and attributable risk factors from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate, age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). The associations between cancers burden and socio-demographic index (SDI) were also analyzed., Results: Compared with 1990, the global incident cases in 2019 were higher by 154.78%, 123.34%, and 169.11% for kidney, bladder, and prostate cancers, respectively. During the 30-year study period, there was a downward trend in ASMR and ASDR for bladder cancer (EAPC = - 0.68 and - 0.83, respectively) and prostate cancer (EAPC = - 0.75 and - 0.71, respectively), but an upward trend for kidney cancer (EAPC = 0.35 and 0.12, respectively). Regions and countries with higher SDI had higher incidence, mortality, and DALYs for all three types of cancers. The burden of bladder and prostate cancers was mainly distributed among older men, whereas the burden of kidney cancer increased among middle-aged men. Smoking related mortality and DALYs decreased, but high body mass index (BMI) and high fasting plasma glucose (FPG) related mortality and DALYs increased among kidney, bladder, and prostate cancers during the study period., Conclusions: Kidney, bladder, and prostate cancers remain major global public health challenges, but with distinct trend for different disease entity across different regions and socioeconomic status. More proactive intervention strategies, at both the administrative and academic levels, based on the dynamic changes, are needed., (© 2021. The Author(s).)

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Ma, Yu, Ouyang, Luo, Pei, Xu, Hu, Mo, Xu, Lan, Shen, Shou, Qian, Feng, Zhao, Jiang, Hu, Zhang, Qian, Wu, Wu, Qiu, Li, Lang, Chen, Chen, Guo, Cao, Jiang, Xia, Le, Zhao, Huang, Zhang, Lv, Hua, Hong, Zheng, Wang, Hu, Chen, Zhang, Tao, Xie, Kuang, Luo, Su, Guo, Wu, Jiang, Zhang, Zhang, Chen, Xu, Guo, Tu, Hu, Yan, Yao, Lou, Jin and the APL Cooperative Group of Zhejiang Province.)

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = -3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function-5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.

In this study, we measure the in-plane transport properties of high-quality Ba(Fe 0.914 Co 0.086 ) 2 As 2 single crystals. Signatures of vortex unbinding Berezinskii-Kosterlitz-Thouless (BKT) transition are shown from both the conventional approach and the Fisher-Fisher-Huse dynamic scaling analysis, in which a characteristic Nelson-Kosterlitz jump is demonstrated. We also observe a non-Hall transverse signal exactly at the superconducting transition, which is explained in terms of guided motion of unbound vortices.

Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method., Methods: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method., Results: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%., Conclusions: For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.

Serine proteinase inhibitor B9 (serpin B9) is a member of the serine protease inhibitor superfamily, which is widely found in animals, plants and microorganisms. Serpin B9 has been reported to protect cells from the immune‑killing effect of granzyme B (GrB) released by lymphocytes. In recent years, an increasing number of studies have indicated that serpin B9 is involved in tumour apoptosis, immune evasion, tumorigenesis, progression, metastasis, drug resistance and even in maintaining the stemness of cancer stem cells (CSCs). Moreover, according to clinical studies, serpin B9 has been demonstrated to be significantly associated with the development of precancerous lesions, a poor prognosis and ineffective therapies, suggesting that serpin B9 may be a potential target for cancer treatment and an indicator of cancer diagnosis; thus, it has begun to attract increased attention from scholars. The present review concisely described the structure and biological functions of the serpin superfamily and serpin B9. In addition, related research on serpins in cancer is discussed in order to provide a comprehensive understanding of the role of serpin B9 in cancer, as well as its clinical significance for cancer diagnosis and prognosis.

Gestational exposure to environmental Cd caused placental angiogenesis impairment and fetal growth restriction (FGR). However, its mechanism remained unclear. This study was to investigate the effects of Cd exposure during pregnancy on placental angiogenesis and its mechanism. Pregnant mice were exposed to CdCl 2 (4.5 mg/kg) on gestational day (GD) 8 with or without melatonin (MT) (5.0 mg/kg), an anti-endoplasmic reticulum stress agent, from GD7 to GD15. Human primary placental trophoblasts and JEG-3 cells were stimulated using CdCl 2 (20 μM) after MT (1 mM) preprocessing. We firstly found MT treatment obviously mitigated environmental Cd-induced placental angiogenesis disorder and reduction of the VEGF-A level. Mechanistically, MT reversed environmental Cd-downregulated the protein expression of VEGF-A via inhibiting glucocorticoid receptor (GR) activation. Notably, our data showed MT treatment antagonized Cd-activated GC/GR signaling via blocking PERK signaling and thereby upregulated VEGF-A and 11β-HSD2 protein expression. Based upon the population case-control study, the levels of VEGF-A and 11β-HSD2 protein in small-for-gestational-age placentae were significantly reduced when compared to appropriate-for-gestational-age placentae. Overall, environmental Cd exposure during gestation impaired placental angiogenesis via PERK-regulated GC/GR signaling in placental trophoblasts. Our findings will provide a basis for prevention and treatment of placental impairments and fetal growth restriction caused by environment toxicants in future., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the effects of high-fat diet on the biological network regulation of gene expression microarray data and key proteins in mouse prostate tissue, and provide some new theoretical evidence for the mechanism of obesity inducing PCa., Methods: From the Gene Expression Omnibus (GEO), we obtained RNAs in the prostate tissue from two groups of C57BL / 6J mice, the normal diet group (n = 5) and high-fat diet group (n = 4). Using the Gene Cloud, Gene-Cloud of Biotechnology Informs (GCBI), GenClip2.0, and Sytoscape 3.5.1, we screened differentially expressed genes, investigated protein interaction networks and biological pathways of differential genes and, from the perspective of transcriptome, explored the effects of high-fat diet on the changes of the molecular network of prostate tissue genes and the molecular biological functions possibly involved., Results: A total of 134 differentially expressed genes were identified, 130 up-regulated and 4 down-regulated, mainly involved in biological functions such as chromosome organization, cell-cell signaling, small molecule biosynthesis and leukocyte activation. The Lck, Prkcb and Cd28 genes in the gene network were of high value, indicating an important relationship with protein synthesis and biological functions, the core node of the protein-protein network, and a high predictive ability of Lck and Cd28., Conclusions: The high-fat diet can induce changes in prostate tissue genes, leading to tumorigenesis.

The objective of this study is to provide comprehensive and up-to-date estimates on the disease burden of BPH in 204 countries and territories between 1990 and 2019. Data about incidence, year lived with disability (YLD), and their age-standardized rates (ASRs) for 21 regions, 5 Socio-demographic Index (SDI) quintiles, 204 countries and territories, and 12 age categories from 1990 to 2019 were obtained from the Global Burden of Disease 2019 study. Estimated annual percentage changes (EAPCs) of the ASRs and the associations between SDI and the ASRs were estimated. The effects of population growth, population aging, and age-specific rate on the changes in the absolute numbers of incidence and YLD were quantified. Globally, there were 11.26 million (95% uncertainty interval [UI]: 8.79, 14.46) new cases and 1.86 million (95%UI: 1.13, 2.78) YLD due to BPH in 2019. The global ASRs of incidence (EAPC: -0.031, 95% CI: -0.050, -0.012) and YLD (EAPC: -0.058, 95% CI: -0.084, -0.031) decreased slightly from 1990 to 2019, whereas the absolute numbers increased dramatically from 1990 (incidence by 105.7% and YLD by 110.6%), mainly driven by the population growth (53.5% for incidence and 54.4% for YLD) and population aging (55.7% for incidence and 63.2% for YLD). The burden of BPH varied markedly among different regions, socioeconomic status, and countries. As the population is growing and aging, great efforts are required to develop effective prevention, treatment and management strategies to meet the high and increasing burden of BPH worldwide.

Hypoxia is a common phenomenon during tumorigenesis and tumour development. In recent years, studies have found that hypoxia‑inducible factor (HIF)‑2α, also referred to as endothelial PAS domain protein‑1, plays an important role in tumours. HIF‑2α is an important oncogene and a critical prognostic indicator in non‑small cell lung cancer. However, no unified conclusion can be drawn concerning HIF‑2α and small cell lung cancer, since few studies to date have focused on their association. An increasing number of studies have confirmed that HIF‑2α is involved in tumorigenesis, cell proliferation, angiogenesis, metastasis, drug resistance and radiotherapy failure in lung cancer. Of note, HIF‑2α plays a crucial role in lung cancer to maintain cancer cell stemness. Based on the importance of HIF‑2α in lung cancer, HIF‑2α‑targeted therapy has been attracting increasing attention. Although this strategy currently appears to be promising in vitro , it has never been assessed as a therapy for lung cancer. The aim of the present review was to summarize the contribution of HIF‑2α to various aspects of lung cancer, as well as its potential as targeted therapy.

Gestational exposure to environmental stress induces fetal growth restriction (FGR), and thereby increasing the risk of infant death and chronic noncommunicable diseases in adults. However, the mechanism by which environmental stress induces FGR remains unclear. Based on case-control study, we found that the reduced level of melatonin (MT), a major secretory product from the pineal gland, was observed in placentae of FGR. This work was to investigate the protective effect of MT on environmental stress-caused FGR and its mechanisms. We used cadmium (Cd) as an environmental stressor to stimulate pregnant mice and thereby establishing a FGR model. The data showed that maternal Cd exposure lowered the P4 concentration in maternal sera, placentae and amniotic fluid, and caused FGR. Correspondingly, the expression of CYP11A1, a critical P4 synthase, was markedly downregulated in Cd-treated placentae. Simultaneously, Cd triggered BNIP3-dependent mitophagy in placental trophoblasts, as determined by the degradation of mitochondrial proteins, including HSP60 and COX IV, and the accumulation of puncta representing co-localization of TOM20 with LC3B or BNIP3 with LC3B. Based on our case-control study, we also found that activated BNIP3-dependent mitophagy and P4 synthesis inhibition occurred in SGA placentae. Most importantly, BNIP3 siRNA reversed Cd-induced P4 synthesis suppression in human placental trophoblasts. It is noteworthy that MT alleviated Cd-caused P4 synthesis suppression and FGR via antagonizing BNIP3-dependent mitophagy in placental trophoblasts. Further results confirmed that MT attenuated Cd-triggered BNIP3-dependent mitophagy via blocking GCN2/ATF4 signaling. Amusingly, Cd triggered oxidative stress and then activating GCN2/ATF4 signaling in placental trophoblasts. As expected, MT obviously suppressed Cd-caused reactive oxygen species (ROS) release. In the present study, we propose a neoteric mechanism by which MT protects against environmental stress-impaired P4 synthesis and fetal growth via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts. As above, MT is a potential therapeutic agent antagonizing environmental stress-induced developmental toxicity., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3β-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Magnesium (Mg) is an abundant and important cation in cells. Plants rely on Mg transporters to take up Mg from the soil, and then Mg is transported to anthers and other organs. Here, we showed that MGT6+/- plants display reduced fertility, while mgt6 plants are fertile. MGT6 is expressed in the anther at the early stages. Pollen mitosis and intine formation are impaired in aborted pollen grains (PGs) of MGT6+/- plants, which is similar to the defective pollen observed in mgt5 and mgt9 mutants. These results suggest that Mg deficiency leads to pollen abortion in MGT6+/- plants. Our data showed that mgt6 organs including buds develop significantly slower and mgt6 stamens accumulate a higher level of Mg, compared with wild-type (WT) and MGT6+/- plants. These results indicate that slower bud development allows mgt6 to accumulate sufficient amounts of Mg in the pollen, explaining why mgt6 is fertile. Furthermore, we found that mgt6 can restore fertility of mgt5 , which has been reported to be male sterile due to defects in Mg transport from the tapetum to microspores and that an additional Mg supply can restore its fertility. Interestingly, mgt5 fertility is recovered when grown under short photoperiod conditions, which is a well-known factor regulating plant fertility. Taken together, these results demonstrate that slow development is a general mechanism to restore mgt s fertility, which allows other redundant magnesium transporter (MGT) members to transport sufficient Mg for pollen formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Qian, Wang, Yu, Guo, Zhao, Wang, Yang, Huang and Yang.)

Cadmium (Cd), a well-known environmental pollutant, can lead to placental insufficiency and fetal growth restriction. However, the underlying mechanism is unknown. The purpose of our study is to explore the effect of Cd on placental angiogenesis and its mechanism using in vitro and in vivo models. Results found that gestational Cd exposure obviously decreased placental weight and impaired placental vascular development in mice. Correspondingly, Cd exposure evidently downregulated the expression of VEGF-A protein (a key indicator of angiogenesis) and progesterone receptor (PR) in placental trophoblasts. Further experiment showed that lentivirus PR overexpression reversed Cd-caused the reduction of VEGF-A level in human placental trophoblasts. In addition, Cd significantly reduced progesterone level, down-regulated the expression of key progesterone synthase (StAR, CYP11A1), and activated mitochondrial stress response and GCN-2/p-eIF2α signaling in placental trophoblasts. Additional experiment showed that GCN-2 siRNA pretreatment markedly alleviated Cd-activated mitochondrial stress response, restored Cd-downregulated the expression of CYP11A1, reversed Cd-reduced the level of progesterone and VEGF-A in human placental trophoblasts. Finally, our case-control study confirmed that impaired placental angiogenesis and reduced progesterone level occurred in all-cause small for gestational age placenta. Taken together, environmental exposure to Cd impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the relationship between microRNA-34b/c single nucleotide polymorphism (SNP) rs4938723 and the risk of male infertility., Methods: This case-control study included 553 males aged 19－40 (29.42 ± 5.09) years with idiopathic infertility, 153 with azoospermia and 400 with oligoasthenospermia, and another 332 normal fertile men aged 19－40 (28.5 4 ± 4.63) years as controls. We collected the clinical data and peripheral blood samples from the subjects, genotyped microRNA-34b/c rs4938723 by Sequenom MassARRAY, and analyzed the relationship between the genotypes of microRNA-34b/c rs4938723 and the risk of male infertility using the logistic regression model., Results: Statistically significant differences were observed between the infertility patients and normal controls in sperm concentration (［18.71 ± 15.19］ vs ［79.91 ± 43.96］ × 10⁶/ml, P < 0.01), the percentage of progressively motile sperm (［13.27 ± 24.52］% vs ［42.82 ± 8.86］%, P < 0.01) and the level of follicle stimulating hormone (［16.09 ± 17.37］ vs ［12.20 ± 4.73］ IU/L, P < 0.01). Compared with the TT genotype, the TC and CC genotypes showed no correlation with male infertility, nor did the genetic locus in the subgroup analysis., Conclusions: No correlation was found between microRNA-34b/c SNP rs4938723 and male infertility, which, however, needs to be further verified by larger-sized samples.

Wheat stem rust, caused by Puccinia graminis f. sp. tritici , is one of the most serious fungal diseases in wheat production, seriously threatening the global supply of wheat and endangering food security. The present study was conducted to evaluate wheat monogenic lines with known Sr genes to the most prevalent P. graminis f. sp. tritici races in China. In addition, wheat lines introduced from the International Maize and Wheat improvement Center (CIMMYT) with resistance to the Ug99 race group were also evaluated with the prevalent Chinese P. graminis f. sp. tritici races. The monogenic lines containing Sr9e , Sr21 , Sr26 , Sr31 , Sr33 , Sr35 , Sr37 , Sr38 , Sr47 , and SrTt3 were effective against races 21C3CTTTM, 34C0MRGSM, and 34C3MTGQM at both seedling and adult-plant stages. In contrast, monogenic lines containing Sr6 , Sr7b , Sr8a , Sr9a , Sr9b , Sr9d , Sr9f , Sr9g , Sr13 , Sr16 , Sr18 , Sr19 , Sr20 , Sr24 , Sr28 , Sr29 , and Sr34 were highly susceptible to these races at both seedling and adult-plant stages. Lines with Sr5 , Sr10 , Sr13 , Sr14 , Sr15 , Sr17 , Sr21 , Sr22 , Sr23 , Sr25 , Sr27 , Sr29 , Sr30 , Sr32 , Sr36 , and Sr39 were resistant to one or more of the tested races. Among the 123 CIMMYT lines, 38 (30.9%) showed varying levels of susceptibility to Chinese P. graminis f. sp. tritici races. The results should be useful for breeding wheat cultivars with resistance to stem rust.

Background: The frequent emergence of the re-positive patients with COVID-19 is a potential threat worldwide. This study aimed to describe data from admission to follow-up for patients with COVID-19 and analyze the possible causes for re-positive nucleic acid tests to provide more scientific basis for reducing the numbers of re-positive patients after discharge. Methods: We retrospectively recorded 15 patients with COVID-19 admitted to the Xianyang Central Hospital, China. The baseline, exposure histories, clinical syndromes, laboratory characteristics, nucleic acid, and follow-up tests were analyzed, and the radiological characteristics of re-positive patient at different periods were compared. Results: Eight (53.33%) patients had the history of travel to Wuhan, four (26.67%) patients had close contact with confirmed patients, and one (6.67%) patient had close contact with suspected patients. After treatment, all patients had two consecutively negative nucleic acid tests and were discharged from hospital. All patients were followed up for more than 14 days, and the average time from discharge to the first follow-up was 14.67 ± 3.31 days (from 9 to 22 days). Most patients showed no clinical symptoms and negative nucleic acid tests, while one patient had an itchy throat, her CT scan showed a light density shadow in the right lower lobe of the lung, and the nucleic acid was once again positive. The second follow-up of the other 14 patients (except the re-positive one) was conducted 20.80 ± 7.78 days (from 13 to 30 days) after discharge, and all of them had negative nucleic acid tests. The positive patient was immediately readmitted and received a new round of treatment. Her family members and colleagues remained healthy until now. Conclusions: The quality of nucleic acid testing reagents should be enhanced, and the training of nucleic acid sampling operators should be strengthened to reduce the false-negative results in the nucleic acid of SARS-CoV-2; the clinical specimens of throat and nasopharynx swabs can be collected at the same time; IgM- and IgG-specific antibodies of SARS-CoV-2 should be carried out for discharged patients; the radiological characteristics should be evaluated strictly; and the discharge standard can be specified according to the baseline and severity of disease of patients., (Copyright © 2020 Qiao, Xu, Zi, Liu, Li, Du, Tian, Liu, Luo and Wang.)

Successful completion of the molting process requires new epidermal growth and ecdysis of the old cuticle in Haemaphysalis longicornis ( H. longicornis ). MicroRNAs (miRNAs) participate in the development of organisms by inhibiting the expression of their target mRNAs. In this study, a novel tick-specific miRNA was identified and denoted hlo-miR-2 that serves as a novel regulator of molting events in H. longicornis nymphs by targeting a cuticular protein. The full length of this cuticular protein was first obtained and named it CPR1. A qRT-PCR analysis showed that hlo-miR-2 and CPR1 exhibit significant tissue and temporal specificity and that their transcription levels are negatively correlated during the molting process. CPR1, as a direct target of hlo-miR-2, was identified by a luciferase reporter assay in vitro . Agomir treatment indicated that the overexpression of hlo-miR-2 significantly reduced the protein expression level of CPR1, decreased the molting rate and delayed the molting time point in H. longicornis nymphs. RNA interference (RNAi) experiments demonstrated that CPR1 was significantly associated with the molting process in H. longicornis nymphs. Phenotypic rescue experiments convincingly showed that hlo-miR-2 participated in molting events by targeting CPR1 in H. longicornis nymphs. In summary, we present evidence demonstrating that miRNAs constitute a novel important regulator of molting events in addition to hormones. The described functional evidence implicating CPR1 in molting events contributes to an improved understanding of the distinct functions of the CPR family in ticks and will aid the development of a promising application of cuticular protein RNAi in tick control., (Copyright © 2020 Liu, Luo, Ren, Qu, Lin, Xu, Ni, Xiao, Chen, Rashid, Wu, Tan, Qiu, Luo, Yin, Wang, Yang, Xiao and Liu.)

The purpose of this study is to analyze the risk factors of sporadic renal hamartoma and establish a risk scoring system, and to intervene in patients with high-risk sporadic renal hamartoma who are prone to rupture and bleeding as soon as possible.Retrospective univariate and multivariate logistic analyzes were conducted for clinical data of 332 sporadic renal hamartoma patients to screen out independent risk factors of tumor rupture. Score of each independent risk factor was calculated. (Calculation formula: the risk coefficient of each factor = the beta regression coefficient of each factor/the minimum value of the beta regression coefficient of all factors, the value of the smallest beta regression coefficient corresponding to all the factors was assigned 1 point. The score of each factor was equal to the risk coefficient of each variable was taken as an integer value by rounding.) The total score was equal to the sum of all factors. Then the area under the receiver operating characteristics (AUC) curve was compared between high risk factors and scoring system. Finally, the scoring system was evaluated by the area under the curve (AUC) and the Hosmer-Lemeshow method in an independent cohort of 130 patients.Factors such as symptoms at presentation, tumor size, tumor blood supply, and tumor growth pattern were significant predictors of sporadic renal angiomyolipoma rupture in both the univariate and multivariate analyses; these predictors were included in the scoring system to predict sporadic renal angiomyolipoma rupture. There were no significant differences in AUCs between high risk factors and scoring system (z = 0.6434, P = .583, AUC = 0.913, and 0.903 for high risk factors and scoring system, respectively). The sporadic renal angiomyolipoma patients who scored >6 points were prone to rupture. AUROC of the scoring system in the validation set was 0.854(95%CI:0.779, 0.928). Using the Hosmer-Lemeshow method, the value of X was 2.916, P = .893, suggesting the scoring system fitted well.A scoring system based on clinical features is simple and effective in predicting sporadic angiolipoma rupture and hemorrhage. When the score is higher than 6 points, the probability of hamartoma rupture and hemorrhage is significantly increased and early intervention is needed.