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Abstract 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.

BackgroundGrowing 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.MethodsWe 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.ResultsTen 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

High temperatures and particulate matter (PM) pollution can make environments uninhabitable. Using air conditioners to cool rooms and air filters to remove PM is effective, but it consumes lots of energy. To save energy, a novel curtain made of polyvinylidene fluoride–hexafluoropropylene (PVDF-HFP) nanofiber membrane has successfully been produced by simple electrospinning technology, which could block PM from outside through natural ventilation and also cool the room by reflecting and scattering sunlight and radiating energy to the outside. The results showed that the curtain was able to effectively reflect sunlight and reduce the subambient temperature by about 10 °C, achieving effective passive radiative cooling. Moreover, the electrospun PVDF-HFP with good piezoelectric properties could be used as a nano-generator to collect the mechanical energy of the wind, and the PVDF-HFP nanofiber films were used as efficient air filtration curtains with 98% filtration efficiency and 64 Pa pressure drop. This simple method to fabricate double energy-saving curtains is more conducive to dissemination.

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.

Abstract 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.

We report a possible coexistence of nontrivial topology and antiferromagnetism in the newly discovered compounds EuCdBi2, with magnetic Eu layer locating above and below Bi square net. The X-ray diffraction on single crystals and powder indicats that this 112-type material crystalizes in space group of I4/mmm, the same as SrMnBi2 and EuMnBi2. Our combined measurements of magnetization, electrical transport and specific heat consistently reveal antiferromagnetic (AFM) transition of Eu2+ moments at TN = 20 K. The Eu moments are not saturated under a field of 7 T at 1.8 K. The anisotropic susceptibility suggests the Eu moments lie in the ab plane, and a metamagnetic (MM) transition is observed near 1 T below TN. Large positive magnetoresistance (MR) present for both H ‖ ab and H ‖ c, which are considered to contain part contributions from Dirac bands. Hall measurements show the electron-hole compensation effect is prominent above 100 K, with a crossover of Hall resistance from negative to positive values at ∼150 K. The fitted mobility of electrons is as high as 3250 cm2 V−1 S−1 at 1.8 K. Interestingly, the rapid increase of carrier density and suppression of mobility appear at around TN, indicating non-negligible interaction between Eu moments and electron/hole bands. EuCdBi2 may provide a new platform to investigate the interplay of topological bands and antiferromagnetic order.

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 PdII 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 CH2Cl2, which allows the recycling of the adsorbent. This work develops a new porous molecular material promising for practical iodine adsorption.

AtRsmD was recently demonstrated to be a chloroplast 16S rRNA methyltransferase (MTase) for the m2G915 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.

Lead (Pb) in soil may accumulate in crops and enter the human body. This study aimed to understand the speciation transformation and accumulation characteristics of exogenous Pb in calcareous soil with or without the application of soil amendments. Field experiments with continuous maize cultivation have been carried out for two years. The results showed that the contents of total Pb were slightly lower in 2016 than in 2015 for the same treatments; however, no significant difference between the years was observed. Soil Pb existed mainly in the residual fraction without exogenous Pb addition, and its proportion was more than 33% of the total soil Pb in the control and Ca treatments. When Pb was added to calcareous soil, Pb existed largely in the oxidizable and reducible fractions during the two-year experimental period, and those fractions made up over 83% of the total Pb. The proportion of the water-soluble Pb, regardless of the addition of Pb, was the lowest and was less than 0.0019% in all treatments, but the addition of Ca and chitosan amendments reduced the water-soluble and exchangeable Pb contents. The Pb content in different parts of maize followed the order root>leaf>stem>grain during the experimental period. Although maize had low transfer and enrichment factors in calcareous soil, which make the Pb content in the grain show no significant difference among the five treatments in the same year, adding Ca and chitosan to calcareous soil can reduce the Pb contents of maize, especially reduce the Pb contents of root, stem and leaf. Therefore, the addition of calcium and chitosan is an effective strategy for reducing Pb availability in calcareous soils.

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.

ObjectiveLimited 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.MethodsWe 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.ResultsPatients 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).ConclusionThis 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.

Objective This paper summarized the experience in treating middle⁃aged and elderly patients with brain trauma⁃induced coagulopathy (BTIC). Methods and Results From January 2015 to May 2019, 3 BTIC patients (50-85 years old) were diagnosed by clinical examination, laboratory coagulation test and CT scan. Trauma ⁃ induced coagulopathy (TIC) was corrected by craniotomy and decompression, and hematoma aspiration. Two cases (Case 1 and Case 2) were successfully treated while Case 3 was dead due to coagulation disorder and irreversible injury of nervous system. Conclusions Early diagnosis and early treatment could prevent the exacerbation of BTIC, even the patient over 80⁃year⁃old may be cured. However, for patients with particularly severe brain damage, there are still many difficulties, and new treatment methods need to be studied. DOI：10.3969/j.issn.1672⁃6731.2019.12.013

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.

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 CdCl2 (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 CdCl2 (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.

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 10 × 109/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.

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.

Abstract Background Cancer stem cells (CSCs), drug-resistant cancer cell subsets, are known to be responsible for tumor metastasis and relapse. The JAK/STAT pathway, activated by SH2 domain, is known to regulate the tumor growth in gastric cancer (GC). Now, this study was designed to examine whether BMX-ARHGAP affects the GC stem cell properties and the underlying regulatory network via JAK/STAT axis. Methods BMX-ARHGAP expression was characterized in GC tissues and cells by RT-qPCR and western blot assay. When BMX-ARHGAP was overexpressed or silenced via plasmids or siRNA transfection, the stem cell properties were assessed by determining stem cell markers CD133, CD44, SOX2 and Nanog, followed by cell sphere and colony formation assays. Subsequently, cell proliferation and invasion were examined by conducting EdU and Transwell assays. The JAK/STAT3 signaling pathway activation was inhibited using AG490. ARHGAP12, BMX exon 10–11, BXM-SH2, JAK2 and STAT3 expression patterns were all determined to examine the regulatory network. The stem cell property in nude mice was also tested. Results BMX-ARHGAP was determined to be enriched in the GC. Overexpression of BMX-ARHGAP resulted in increased expression of CD133, CD44, SOX2 and Nanog protein, and accelerated proliferation and invasion of CD133+CD44+ cells as well as facilitated self-renewal potential of GC cells. However, the inhibition of the JAK/STAT3 signaling pathway reversed the stimulating effect of BMX-ARHGAP on proliferative and invasion abilities of CD133+CD44+ cells. The overexpression of BMX-ARHGAP was suggested to increase the BMX-SH2 protein expression via ARHGAP 5′UTR, and activate the JAK/STAT3 signaling pathway. Also, BMX-ARHGAP promoted tumor growth in nude mice. Conclusions The aforementioned results demonstrated that the BMX-ARHGAP-dependent SH2 domain-JAK/STAT3 axis mediates the maintenance of GC stem cells, benefiting the development of new potential therapeutic targets for GC.

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.

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 amniotic fluids 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 placental trophoblasts. 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.

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 mgts fertility, which allows other redundant magnesium transporter (MGT) members to transport sufficient Mg for pollen formation.

It is important for energy enterprises to research on the investment potential of the energy markets in countries along the “Belt and Road,” which can help them optimize the regional investment structure, reduce investment risks, and conform to the development trend of “going global.” Therefore, we construct an investment potential assessment system of 29 indexes including five dimensions: politics, economy, society, energy, and cooperation and assess energy investment potential of 48 sample countries along the “Belt and Road” using principal component analysis to provide reference meanings for energy enterprises. The results show that the assessment results of investment potential are affected by a combination of multiple indexes. In addition, compared with Central Asia and South Asia, which have weak economic foundations and greater political and legal risks, the investment potential of Central and Eastern Europe and some emerging economies in Southeast Asia is higher.

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.

A 60-year-old male patient presented with a serum α-fetoprotein (AFP) level of 2940.5 ng/mL accompanied by a significant increase in serum globulin. Hepatitis B virus (HBV) DNA was 2.85 × 10 3 (normal value

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.

ObjectiveTo systematically evaluate the quality of clinical practice guidelines (CPG) for medically treating benign prostatic hyperplasia (BPH), and to compare the context of recommendations in order to provide references for clinical application.MethodsWe searched databases of National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, and Medlive from their establishment to October 13, 2019, to collect evidence-based guidelines and/or consensus on BPH. Method quality of included guidelines was assessed according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, and differences and similarities among recommendations were compared.ResultsA total of 22 guidelines were included, of which eight were updated versions. According to the AGREE II instrument, the median score of scope and purpose, stakeholder involvement, rigor of formulate, clarity of presentation, applicability, and editorial independence was 71.5%, 41%, 25%, 64%, 18%, and 28%, respectively. Based on recommendations for medical treatment, almost all guidelines recommended α1-blockers and 5α-reductase inhibitors, and most guidelines also recommended muscarinic receptor antagonists. In terms of drug combination therapy, most guidelines recommended “α1 blockers and 5α-reductase inhibitors”, and some guidelines also recommended “α1 blockers and muscarinic receptor antagonists”.ConclusionThe recommendations from different guidelines were basically similar, only showing conflicts in some areas. The quality of included guidelines remains to be unified, and their context can provide valuable implications for development or improvement.

In the present work, a unique gradient cooling heat treatment process (GCHT) for a Mn-Si-Cr-B bainitic cast steel was developed, and microstructure and mechanical properties were examined by OM, SEM, EBSD and a uniaxial tensile test. The results showed that the structural-gradient-material (SGM) with a gradient microstructure from granular bainite to martensite was successfully produced, and it exhibited a good ductility (~13.8%) at one end and an excellent ultimate strength (~1,720 MPa) at the other end. In between the bainite and martensite, a transition region with a superior combination of tensile strength and ductility (1,700 MPa and 11.1%) was obtained, which is different from the normal knowledge of a brittle transition region. Moreover, through changing the gradient of cooling rate, the optimized SGM with a new gradient microstructure from pearlite to martensite showed a more stable structural gradient and an improved ductility (22.8%) at one end. The microstructure variation in the sample was mainly related to the carbon diffusion rate during heat treatment, and the diffusion rate could be controlled by regulating the cooling velocity. Therefore, the SGMs with different gradient microstructures could be designed to meet the needs of different properties. As a result, this work provides a new approach for preparation of the gradient structured steel, which has potential for practical application for dual-property automobile parts.

Blepharokeratoconjunctivitis(BKC)refers to a group of inflammatory lesions secondary to chronic blepharitis in cornea and(or)conjunctiva, is very common in clinic. At the same time, this kind of disease is easily misdiagnosed and missed diagnosed, which causing the management of patient were delayed. The characteristic of BKC is that the patient's condition is prolonged unhealed and unreasonable treatment can result in irreversible damage to the visual function of the patient. In recent years, with the public's understanding of ocular surface diseases has deepened, they also emphasized the influence of BKC to eye health. Although a large number of clinical studies have been carried out on the diagnosis and treatment of BKC, at present there is no unified standard of diagnosis and treatment for it. Consulting the relevant literature and combined with current research status, the diagnosis and treatment of BKC are reviewed in this paper.

Given the challenges facing the cyberspace of the nation, this paper presents the tripartite theory of cyberspace, based on the status quo of cyberspace. Corresponding strategies and a research architecture are proposed for common public networks (C space), secure classified networks (S space), and key infrastructure networks (K space), based on their individual characteristics. The features and security requirements of these networks are then discussed. Taking C space as an example, we introduce the SMCRC (which stands for “situation awareness, monitoring and management, cooperative defense, response and recovery, and countermeasures and traceback”) loop for constructing a cyberspace security ecosystem. Following a discussion on its characteristics and information exchange, our analysis focuses on the critical technologies of the SMCRC loop. To obtain more insight into national cyberspace security, special attention should be paid to global sensing and precise mapping, continuous detection and active management, cross-domain cooperation and systematic defense, autonomous response and rapid processing, and accurate traceback and countermeasure deterrence. Keywords: Cyberspace security ecosystem, SMCRC loop, Tripartite theory of cyberspace

Abstract Background In Arabidopsis, the tapetum and microsporocytes are critical for pollen formation. Previous studies have shown that ARF17 is expressed in microsporocytes and tetrads and directly regulates tetrad wall synthesis for pollen formation. ARF17 is the direct target of miR160, and promoterARF17::5mARF17 (5mARF17/WT) transgenic plants, which have five silent mutations within the miR160-complementary domain, are sterile. Results Here, we found that ARF17 is also expressed in the tapetum, which was defective in arf17 mutants. Compared with arf17 mutants, 5mARF17/WT plants had abnormal tapetal cells and tetrads but were less vacuolated in the tapetum. Immunocytochemical assays showed that the ARF17 protein over-accumulated in tapetum, microsporocytes and tetrads of 5mARF17/WT plants at early anther stages, but its expression pattern was not affected during anther development. 5mARF17 driven by its native promoter did not rescue the arf17 male-sterile phenotype. The expression of 5mARF17 driven by the tapetum-specific promoter A9 led to a defective tapetum and male sterility in transgenic plants. These results suggest that the overexpression of ARF17 in the tapetum and microsporocytes of 5mARF17/WT plants leads to male sterility. Microarray data revealed that an abundance of genes involved in transcription and translation are ectopically expressed in 5mARF17/WT plants. Conclusions Our work shows that ARF17 plays an essential role in anther development and pollen formation, and ARF17 expression under miR160 regulation is critical for its function during anther development.

In this study, we measure the in-plane transport properties of high-quality Ba(Fe0.914Co0.086)2As2 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.

A novel role analysis method for network domain users was proposed.Firstly,the algorithm used ISODATA algorithm to cluster network events for user behavior analysis,on the basis of conditions,the method search relationships between varieties of grouping sets in the network instance,and identify each user role in the performing process of network instance.Finally,simulation results show that the effectiveness of the proposed algorithm can distinguish the network user hierarchy and obtain the dominant roles about network users.

To determine stem rust resistance genes of wheat varieties in Yunnan province, 11 Chinese strains of Puccinia graminis f.sp. tritici with different virulence and 1 artificial mutant strain were used in 110 wheat varieties. The results indicated that among the 45 Sr genes, Sr31, Sr5, SrTmp, Sr30, Sr36, Sr8a, Sr11, Sr24, Sr29, Sr34, Sr9e, Sr26, Sr38, Sr47, and SrTt3 were characterised in 55 wheat varieties singly or in combination. Sr5, Sr31, SrTmp, Sr36, and Sr30 were contained in 17, 16, 5, 5, and 3 cultivars, respectively. Six cultivars contained Sr24 and/or Sr34. Three plant materials likely contained one or more of Sr8a, Sr11, Sr34, and Sr23 genes as well as other unknown genes. The 16 immune or highly resistant varieties contained one or more of Sr9e, Sr26, Sr38, Sr47, SrTt3, and other unknown resistance genes. The reaction types on 22 of the tested cultivars were different from those on Sr genes tested, and their resistance genes could not be analysed. Additionally, 17 varieties were susceptible to all the tested strains, having no postulation value. Our study provides a basis for improved breeding of stem rust resistant wheat in China.

Various studies have reported that galanin can promote axonal regeneration of dorsal root ganglion neurons in vitro and inhibit neuropathic pain. However, little is known about its effects on diabetic peripheral neuropathy, and in vivo experimental data are lacking. We hypothesized that repeated applications of exogenous galanin over an extended time frame may also repair nerve damage in diabetic peripheral neuropathy, and relieve pain in vivo. We found that neuropathic pain occurred in streptozotocin-induced diabetic rats and was more severe after sciatic nerve pinch injury at 14 and 28 days than in diabetic sham-operated rats. Treatment with exogenous galanin alleviated the neuropathic pain and promoted sciatic nerve regeneration more effectively in diabetic rats than in non-diabetic rats after sciatic nerve pinch injury. This was accompanied by changes in the levels of endogenous galanin, and its receptors galanin receptor 1 and galanin receptor 2 in the dorsal root ganglia and the spinal dorsal horn when compared with nerve pinch normal rats. Our results show that application of exogenous galanin daily for 28 days can promote the regeneration of injured sciatic nerves, and alleviate neuropathic pain in diabetic rats.

To characterize the incidence and risk factors for monochorionic diamniotic(MC-DA) twinning after assisted reproductive technologies (ART).Retrospective population-based study.The study was conducted in China; Department of Reproductive Medicine Center at The First Affiliated Hospital of Anhui Medical University.A cohort of 8860 clinical pregnancies after embryo transfer (ET) carried out in our center between 2011 and 2016 were retrospectively analyzed for the incidence of MC-DA twinning.Logistic regression was used to model the effect on the incidence of MC-DA twinning after ART. Different clinical data (maternal age) and laboratory procedures (type of ET (fresh versus frozen), insemination (IVF or ICSI)), embryo stage at time of ET (cleavage or blastocyst)) on the incidence of MC-DA twinning were evaluated.Monochorionic-diamniotic pregnancies were identified when more than one fetal poles was visualized in one gestational sac via trans-vaginal ultrasound at early first-trimester (7 to 8 weeks).The overall MC-DA twinning rate was 2.55% (226/8860). Eighty one MC-DA twinnings occurred in the fresh cycles and 145 in the frozen cycles (2.67% vs. 2.49%). MC-DA twinning incidence showed no significant difference whether ICSI was performed or not (2.79% vs. 2.44%). The MZT that resulted from single embryo transfer (SET) cycles (1.99%) was slightly lower than multiple embryo transfer cycles (2.61%),but with non-significance. However, women

Callose synthesis is critical for the formation of the pollen wall pattern. CalS5 is thought to be the major synthethase for the callose wall. In the Arabidopsis anther, ARF17 regulates the expression of CalS5 and is the target of miR160. Plants expressing miR160-resistant ARF17 (35S:5mARF17 lines) with increased ARF17 mRNA levels display male sterility. Here we report a zinc finger family gene, AtTTP, which is involved in miR160 maturation and callose synthesis in Arabidopsis. AtTTP is expressed in microsporocytes, tetrads and tapetal cells in the anther. Over-expression lines of AtTTP (AtTTP-OE line) exhibited reduced male fertility. CalS5 expression was tremendously reduced and the tetrad callose wall became much thinner in the AtTTP-OE line. Northern blotting hybridization and quantitative RT-PCR analysis revealed that miR160 was decreased, while the expression of ARF17 was increased in the AtTTP-OE line. Based on these results, we propose that AtTTP associates with miR160 in order to regulate the ARF17 expression needed for callose synthesis and pollen wall formation.

BACKGROUND: Increased vascular permeability is a hallmark feature in severe dengue virus (DV) infection, and dysfunction of endothelial cells has been speculated to contribute in the pathogenesis of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Rho-family GTPase Rac1 is a significant element of endothelial barrier function regulation and has been implicated in the regulation of actin remodeling and intercellular junction formation. Yet there is little evidence linking Rac1 GTPase to alteration in endothelial cell function induced by DV infection. METHODS AND FINDINGS: Here, we showed that actin is essential for DV serotype 2 (DV2) entry into and release from ECV304 cells, and Rac1 signaling is involved these processes. At early infection, actin cytoskeleton rearranged significantly during 1 hour post infection, and disrupting actin filament dynamics with jasplakinolide or cytochalasin D reduced DV2 entry. DV2 entry induced reduction of Rac1 activity within 1 hour post infection. The expression of dominant-negative forms of Rac1 established that DV2 entry is negatively regulated by Rac1. At late infection, actin drugs also inhibited the DV2 release and induced accumulation of viral proteins in the cytoplasm. Meanwhile, the activity of Rac1 increased significantly with the progression of DV2 infection and was up-regulated in transfected cells expressing E protein. Confocal microscopy showed that DV2 E protein was closely associated with either actin or Rac1 in DV2-infected cells. The interaction between E protein and actin was further confirmed by co-immunoprecipitation assay. CONCLUSIONS: These results defined roles for actin integrity in DV2 entry and release, and indicated evidence for the participation of Rac1 signaling pathways in DV2-induced actin reorganizations and E-actin interaction. Our results may provide further insight into the pathogenesis of DHF/DSS.