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Drought is one of the most widespread and devastating extreme climate events when water availability is significantly below normal levels for a long period. In recent years, the Haihe River Basin has been threatened by intensified droughts. Therefore, characterization of droughts in the basin is of great importance for sustainable water resources management. In this study, two multi-scalar drought indices, the standardized precipitation evapotranspiration index (SPEI) with potential evapotranspiration calculated by the Penman–Monteith equation and the standardized precipitation index (SPI), were used to evaluate the spatiotemporal variations of drought characteristics from 1961 to 2017 in the Haihe River Basin. In addition, the large-scale atmospheric circulation patterns were used to further explore the potential links between drought trends and climatic anomalies. An increasing tendency in drought duration was detected over the Haihe River Basin with frequent drought events occurring in the period from 1997 to 2003. The results derived from both SPEI and SPI demonstrated that summer droughts were significantly intensified. The analysis of large-scale atmospheric circulation patterns indicated that the intensified summer droughts could be attributed to the positive geopotential height anomalies in Asian mid-high latitudes and the insufficient water vapor fluxes transported from the south.

Abstract Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy.

Recent studies indicate that host immune responses are dysregulated with either myeloid cell compartment or lymphocyte composition being disturbed in COVID-19. This study aimed to assess the impact of SARS-CoV-2 viral infection on the composition of circulating immune cells in severe COVID-19 patients. In this retrospective single-center cohort, 71 out of 87 COVID-19 patients admitted to the intense care unit for oxygen treatment were included in this study. Demographics, clinical features, comorbidities, and laboratory findings were collected on admission. Out of the 71 patients, 5 died from COVID-19. Compared with survived patients, deceased patients showed higher blood cell counts of neutrophils and monocytes but lower cell counts of lymphocytes. Intriguingly, the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and basophil-to-lymphocyte ratio (BLR) were markedly higher in deceased patients compared to survived patients. Furthermore, the lymphocyte counts were negatively correlated with D-dimer levels, while the ratios between myeloid cells and lymphocyte (NLR, MLR, and BLR) were positively correlated with D-dimer levels. Our findings revealed that the ratios between myeloid cells and lymphocytes were highly correlated with coagulation status and patient mortality in severe COVID-19.

Matrix metalloproteinase-9 (MMP-9), one of the most investigated and studied biomarkers of the MMPs family, is a zinc-dependent proteolytic metalloenzyme whose primary function is degrading the extracellular matrix (ECM). It has been proved that MMP-9 expression elevates in multiple pathological conditions, including thyroid carcinoma. MMP-9 has a detectable higher level in malignant or metastatic thyroid tumor tissues than in normal or benign tissues and acts as an additional marker to distinguish different tumor stages because of its close correlations with clinical features, such as lymph node metastasis, TNM stage, tumor size and so on. Natural and non-natural MMP-9 inhibitors suppress its expression, block the progression of diseases, and play a role in therapy consequently. MMP-9 inhibitory molecules also assist in treating thyroid tumors by suppressing the proliferation, invasion, migration, metastasis, viability, adhesion, motility, epithelial-mesenchymal transition (EMT), and other risk factors of different thyroid cancer cells. In a word, discovering and designing MMP-9 inhibitors provide great therapeutic effects and promising clinical values in various types of thyroid carcinoma.

This study measured the lifecycle carbon emissions of buildings in 30 Chinese provinces from 2005 to 2020 and decomposed the drivers of carbon emissions in the materialization stage and operation stage of building, respectively, using the Stochastic Impacts with the Regression on Population, Affluence, and Technology (STIRPAT) model in order to investigate the drivers of carbon emissions and their spatial influence effects in the building sector. The spatial Durbin model (SDM) was used to thoroughly investigate the spatial effects of carbon emissions and their drivers in the building sector under geographic and economic distances. According to the findings, China’s building sector has a high concentration of carbon emissions in the east and a low concentration in the west. There is also a sizable spatial autocorrelation, and the spatial spillover effects in the materialization and operation stages shift in opposite directions. To help the building sector to achieve the carbon peaking and neutrality goals, specific policy recommendations are made based on the study’s findings.

With the development of a low-carbon economy, zero-energy structures will become prevalent and take center stage in the construction industry. This paper uses the CiteSpace software to create knowledge maps of authors, institutions and keywords, and then examined and commented on research publications regarding zero-energy buildings in order to understand the research state and development trends of zero-energy buildings. The findings demonstrate that: (1) Since its inception in 2000, research on zero-energy buildings has advanced significantly; (2) A subject analysis approach is used to identify development trends and research emphasis, and the four research areas with the most papers published are energy fuels, construction building technology, civil engineering and green sustainable science technology; (3) China, the United States and Italy are the countries with the most activity in zero-energy building research; (4) Out of the eight most prominent keywords for the study subjects, the design of zero-energy buildings, the estimation of the carbon emissions of zero-energy buildings, the technical challenges of zero-energy buildings and the follow-up energy-saving measures of zero-energy buildings are the four fundamental topics covered in the most cited papers; (5) There are three obstacles to the development of zero-carbon buildings: unclear standards, immature technology and insufficient development momentum. The following three problems should receive more attention in the future: how to develop a widely accepted zero-carbon building standard; how to coordinate national support to achieve technological breakthroughs; and the establishment of an effective incentive mechanism at the international and national levels to promote the development of zero-carbon buildings.

Numerical simulations were carried out to assess the technical and economic feasibility of a solar water desalination system that has a novel hybrid Concentrating Photovoltaic Thermal (CPVT) collector coupled with a Vacuum Membrane Distillation (VMD) process. A special characteristic of this CPVT is its triangular receiver with PV cells facing the reflecting surface. This type of receiver has the advantage of generating more electricity with less PV surface area and great potential to be used to hybridize conventional parabolic thermal collectors. TRNSYS was employed to analyze the annual performance of the CPVT-VMD system evaluating parameters such as solar fraction, specific permeate production and specific energy production for different coastal cities. In the dynamic simulations, local annual weather data and specific information about the characteristics and operating conditions of a real CPVT collector and a VMD module were considered. From the parametric analysis the optimal surface area of collectors and the input temperature of the VDM module were determined. A maximum specific permeate of 218.410 m 3/m2VMD for Acapulco, MX, and a minimum of 170.365 m 3/m2VMD for Singapore, SG, were achieved for the proposed CPVT-VMD system of four solar collectors with an operating set temperature of 55 °C. An economic profit was found after 7 years for Acapulco city, which showed great potential to use solar energy from hybrid CPVT collectors for a VMD process to provide freshwater in coastal cities.

BACKGROUND: Bronchial anthracofibrosis is a common disease that has been reported in the past. We aim to summarize the clinical characteristics of bronchial anthracofibrosis combined with tuberculosis infection to reduce missed diagnosis.METHODS: The clinical features of two cases of bronchial anthracofibrosis combined with tuberculosis were analyzed retrospectively, and relevant studies were reviewed.RESULTS: The two patients were both elderly individuals who presented with chronic cough and expectoration. Pigmentation in the bronchus mucosa and stenosis of lumen were observed during bronchoscopy. Tuberculosis infection was confirmed by biopsy. The symptoms were remarkably relieved and no recurrence was found after anti-tuberculosis treatment.CONCLUSION: Bronchial anthracofibrosis may be combined with tuberculosis. To avoid misdiagnosis, we should be aware of possible tuberculosis infection when patients are diagnosed with bronchial anthracofibrosis.

MarvelD3, a recently identified tight junction membrane protein, could be associated with hepatocellular carcinoma (HCC). We aimed to investigate the role of marvelD3 in Epithelial–Mesenchymal Transition (EMT) and migration of HCC and explore the underlying molecular mechanisms. First, we assessed marvlD3 expression in HCC and normal liver tissues and found loss of marvelD3 expression was significantly correlated with the occurrence and TNM stage of HCC. Second, we detected that marvelD3 was downregulated in HCC cells with transforming growth factor β1 and snail/slug-induced EMT. Finally, we analyzed expression of marvelD3 protein was significantly associated with EMT and the NF-κB signaling pathway. Our study demonstrated that MarvelD3 inhibited EMT and migration of HCC cells along with inhibiting NF-κB signaling pathway. Abbreviations: HCC, Hepatocellular carcinoma; TJ, Tight junction; MARVEL, MAL and related proteins for vesicle trafficking and membrane link; EMT, Epithelial–mesenchymal transition; NF-κB, Nuclear factor kappa B; TAMPs, Tight junction-associated marvel proteins; TGF-β1, Transforming growth factor-β1; MMP9, matrix metallopeptidase 9; RT-PCR, Real-time PCR; IHC, Immunohistochemistry; IF, Immunofluorescence.

Exciton hopping: Energy travels far in perovskite nanocrystal films Excitons quasi-particles in methylammonium lead bromide perovskite nanocrystal films can travel over a surprisingly long distance. Tze Chien Sum and colleagues at Singapore’s Nanyang Technological University uncovered that the long diffusion lengths of more than one micrometer are largely due to excitons hopping from one nanocrystal to another. They are also caused, albeit to a lesser degree, by photon recycling, in which absorbed photons are re-emitted within the material, generating more charge carriers. The team found that perovskite nanocrystals connected by octylamine ligands showed the longest exciton hopping range compared to those connected by hexylamine or oleylamine ligands. The findings demonstrate the potential of lead halide perovskite nanocrystal films for fabricating smaller, faster, and more energy-efficient electronic devices. They also improve the basic understanding of the mechanisms behind long-range energy transport in these films.

Intra-tumor heterogeneity is widely accepted as one of the key factors, which hinders cancer patients from achieving full recovery. Especially, cancer stem cells (CSCs) may exhibit self-renewal capacity, which makes it harder for complete elimination of tumor. Therefore, simultaneously inhibiting CSCs and non-CSCs in tumors becomes a promising strategy to obtain sustainable anticancer efficacy. Salinomycin (Sal) was reported to be critical to inhibit CSCs. However, the poor bioavailability and catastrophic side effects brought about limitations to clinical practice. To solve this problem, we previously constructed gelatinase-stimuli nanoparticles composed of nontoxic, biocompatible polyethylene glycol-polycaprolactone (PEG-PCL) copolymer with a gelatinase-cleavable peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG) inserted between the two blocks of the copolymer. By applying our “smart” gelatinase-responsive nanoparticles for Sal delivery, we have demonstrated specific accumulation in tumor, anti-CSCs ability and reduced toxicity of Sal-NPs in our previous study. In the present study, we synthesized Sal-Docetaxel-loaded gelatinase-stimuli nanoparticles (Sal-Doc NP) and confirmed single emulsion as the optimal method of producing Sal-Doc NPs (Sal-Doc SE-NP) in comparison with nanoprecipitation. Sal-Doc SE-NPs inhibited both CSCs and non-CSCs in mice transplanted with cervical cancer, and might be associated with enhanced restriction of epithelial-mesenchymal transition (EMT) pathway. Besides, the tumorigenic capacity and growing speed were obviously suppressed in Sal-Doc-SE-NPs-treated group in rechallenge experiment. Our results suggest that Sal-Doc-loaded gelatinase-stimuli nanoparticles could be a promising strategy to enhance antitumor efficacy and reduce side effects by simultaneously suppressing CSCs and non-CSCs.

Objectives: The aim of this study was to assess knowledge, attitudes and practices amongst public health undergraduates in relation to antimicrobial resistance (AMR) in China. Methods: A cross-sectional survey was conducted amongst all final-year public health undergraduates from 18 universities across China. A structured questionnaire was used to collect information on AMR-related knowledge, attitudes and practices, whilst multivariable linear and logistic regressions were employed to detect associations among these three aspects. Results: A total of 1115 participants were included in this study. The mean ± standard deviation AMR knowledge score was 7.68 ± 2.56. Moreover, 75.2% of students had performed incorrect antimicrobial practice. Studying in a key university [slope = 1.49, 95% confidence interval (CI) 0.71–2.27], being male (slope = 0.36, 95% CI 0.02–0.70), having clinical experience (slope = 1.71, 95% CI 1.13–2.30) and having an affirmative attitude towards AMR were positively associated with knowledge score. Knowledge score was also positively associated with AMR practice (odds ratio = 1.07, 95% CI 1.00–1.13). Conclusions: A knowledge gap in relation to AMR was determined among Chinese public health students. This gap is associated with attitudes towards AMR and in turn influences antimicrobial use. It is clear that additional measures are needed in the curriculum, including additional AMR-specific clinical practices.

Abstract Novel coronavirus 2019 (COVID-19) infection is a global public health issue, that has now affected more than 200 countries worldwide and caused a second wave of pandemic. Severe adult respiratory syndrome-CoV-2 (SARS-CoV-2) pneumonia is associated with a high risk of mortality. However, prognostic factors predicting poor clinical outcomes of individual patients with SARS-CoV-2 pneumonia remain under intensive investigation. We conducted a retrospective, multicenter study of patients with SARS-CoV-2 who were admitted to four hospitals in Wuhan, China from December 2019 to February 2020. Mortality at the end of the follow up period was the primary outcome. Factors predicting mortality were also assessed and a prognostic model was developed, calibrated and validated. The study included 492 patients with SARS-CoV-2 who were divided into three cohorts: the training cohort (n = 237), the validation cohort 1 (n = 120), and the validation cohort 2 (n = 135). Multivariate analysis showed that five clinical parameters were predictive of mortality at the end of follow up period, including advanced age [odds ratio (OR), 1.1/years increase (p

Understanding how external water affects the water quality of target water bodies is an important prerequisite for predicting water quality changes and formulating pollutant reduction plans. Using the EFDC modeling system platform, this study constructed the hydrodynamic and pollutant dispersion and diffusion models of Zhangze Reservoir, and by using the hydrology and water quality data from 2013 to 2018, this study examines the different water quality responses of Zhangze Reservoir under different inflow water control scenarios. The results show that the simulated value of the hydrological station is basically consistent with the measured value of the hydrological station. Under the current Class III water quality requirements for Zhangze Reservoir, direct inflow of effluent from the wastewater treatment plant of the main urban area into the reservoir will have a significant impact on the water quality. When the effluent is purified through constructed wetlands, it significantly improves the water quality of the reservoir, but the concentration of TN and TP still cannot reach the Class III standard in the short term,. When all rivers entering the reservoir meet the standard and the effluent from the wastewater treatment plant in the main urban area does not enter the reservoir, the content of COD, ammonia nitrogen and TP in water will reach the Class III standard, but reducing the TN content to meet the standard requirement will be difficult within 3 years.

Commonly, phased array antennas are used to provide spatial resolution for direction of arrival (DOA) estimations. However, the phase‐array‐based DOA estimations usually require complicated system architecture and signal processing. Digital programmable metasurfaces (DPMs) can realize flexible spatial modulations of electromagnetic (EM) waves without using massive transceivers, and hence can be used for DOA estimations with much simplified architectures. Here, a mechanism of DPM‐based DOA estimations at Ka band is proposed. A reflective DPM is designed to produce a series of dual beams in random, so as to establish a sensing matrix and sample the incident wave. Orthogonal matched pursuit algorithm is used to estimate DOA from the sparsely sampled datasets. The performances of the DPM‐based DOA estimations are demonstrated by simulations and experiments for the cases of single source and double sources. This work promotes the development of DPMs and is expected to find important applications in radar and wireless communication systems, as well as the joint radar and communication systems.

Background The KT/HAK/KUP (KUP) transporters play important roles in potassium (K+) uptake and translocation, regulation of osmotic potential, salt tolerance, root morphogenesis and plant development. However, the KUP family has not been systematically studied in the typical halophyte Salicornia europaea L., and the specific expression patterns of SeKUPs under NaCl condition and K+ deficiency are unknown. Methods In this study, SeKUPs were screened from PacBio transcriptome data of Salicornia europaea L. using bioinformatics. The identification, phylogenetic analysis and prediction of conserved motifs of SeKUPs were extensively explored. Moreover, the expression levels of 24 selected SeKUPs were assayed by real-time quantitative polymerase chain reaction (RT-qPCR). Results In this study, a total of 24 putative SeKUPs were identified in S. europaea. Nineteen SeKUPs with the fixed domain EA[ML]FADL were used to construct the phylogenetic tree, and they were divided into four clusters (clusters I–IV). MEME analysis identified 10 motifs in S. europaea, and the motif analysis suggested that 19 of the identified SeKUPs had at least four K+ transporter motifs existed in all SeKUPs (with the exception of SeKUP-2). The RT-qPCR analysis showed that the expression levels of most SeKUPs were significantly up-regulated in S. europaea when they were exposed to K+ deficiency and high salinity, implying that these SeKUPs may play a key role in the absorption and transport of K+ and Na+ in S. europaea. Discussions Our results laid the foundation for revealing the salt tolerance mechanism of SeKUPs, and provided key candidate genes for further studies on the function of KUP family in S. europaea.

As one of the serious environmental problems worldwide, acid rain (AR) has always caused continuous damage to the forestry ecosystem. Studies have shown that AR can leach calcium ions from plants and soil. Calcium (Ca) is also a crucial regulator of the plant stress response, whereas there are few reports on how Ca regulates the response of AR-resistant woody plants to AR stress. In this study, by setting different exogenous Ca levels, we study the physiological and molecular mechanism of Ca in regulating the Taxus wallichiana var. mairei response to AR stress. Our results showed that low Ca level leads to photosynthesis, and antioxidant defense system decreases in T. wallichiana var. mairei leaves; however, these negative effects could be reversed at high Ca level. In addition, proteomic analyses identified 44 differentially expressed proteins in different Ca level treatments of T. wallichiana var. mairei under AR stress. These proteins were classified into seven groups, which include metabolic process, photosynthesis and energy pathway, cell rescue and defense, transcription and translation, protein modification and degradation, signal transduction, etc. Furthermore, the study found that low Ca level leads to an obvious increase of Ca-related gene expression under AR stress in T. wallichiana var. mairei using qRT-PCR analyses and however can be reversed at high Ca level. These findings would enrich and extend the Ca signaling pathways of AR stress in AR-resistant woody plants and are expected to have important theoretical and practical significance in revealing the mechanism of woody plants tolerating AR stress and protecting forestry ecosystem in soil environment under different Ca levels.

Abstract Tenofovir disoproxil fumarate is a recommended first‐line therapy for patients with chronic hepatitis B, although the frequent Tenofovir disoproxil fumarate related adverse drug reactions are nephrotoxicity and bone toxicity. We described the case of a 21‐year‐old Han Chinese male patient with chronic hepatitis B with tenofovir disoproxil fumarate‐associated osteopenia. The patient presented osteopenia at the site of his femoral neck with bone mineral density 0.865g/cm2 (Z = −1.9) in January 2020. Nine months after switching to TAF, bone mineral density at left femoral neck improved to 0.978g/cm2 (Z = −1.0) in September 2020. Bone mineral density of this patients was normal in January 2021. This is the first report in very young man presenting tenofovir disoproxil fumarate‐associated osteopenia.

Some of the mutant peptides produced by gene mutation transcription and translation have the ability to induce specific T cells, which are called new antigens. Neoantigen-based peptide, DNA, RNA, and dendritic cell vaccines have been used in the clinic. In this paper, we describe a lung metastasis of a phyllodes tumor patient demonstrating pathological complete response following treatment containing personalized multi-epitope peptide neoantigen nano-vaccine. Based on whole-exome sequencing (WES), RNA sequencing, and new antigen prediction, several mutated peptide fragments were predicted to bind to the patient’s human leukocyte antigen (HLA) allotypes, including ten peptides with high predicted binding affinity for six genes. The pulmonary metastases remained stable after the four cycles of anti-PD1 and anlotinib. After the addition of the multi-epitope peptide neoantigen nano-vaccine, the tumor began to collapse and contracture developed, accompanied by a decrease of tumor markers to normal, and complete pathological remission was achieved. With the use of the vaccination, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was used every time, and low-dose cyclophosphamide was injected every 3 weeks to improve efficacy. Peripheral blood immune monitoring demonstrated immune reactivity against a series of peptides, with the most robust post-vaccine T-cell response detected against the HLA-DRB1*0901-restricted SLC44A5 V54F peptide.

Abstract Background The survival benefits of perioperative chemoradiotherapy (PCRT) and perioperative chemotherapy (PCT) for resectable gastric cancer (GC) patients remain unclear. This study aimed to compare the effects of PCRT and PCT in patients with resectable GC and develop a nomogram to evaluate the prognosis and disease risk of patients. Methods A total of 6890 patients with stage IB‐IIIC GC from 2010 to 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. Univariate Cox proportional hazards regression analyses were performed to evaluate the prognostic value of involved variables. A new nomogram was constructed based on development cohort and validated by an external validation cohort. The clinical practicability and accuracy were assessed by concordance index (C‐index), calibration plot, and receiver operating characteristic (ROC) curve. Results A better prognosis was obtained for patients with stage III GC treated with PCRT compared with those treated with PCT. Additionally, patients with grade III/IV, diffuse type GC, distal gastric cancer (DGC), tumor size >34 millimeters, or positive lymph nodes were more likely to benefit from PCRT. Multivariate analyses indicated that age, grade, tumor size, T stage, N stage, and comprehensive treatment were independent covariates. Excellent agreement of calibration plots and good discrimination power were obtained using the nomogram. The nomogram achieved a better net benefit than the 8th edition AJCC TNM staging. An online version was built based on the nomogram for convenient clinical use. Conclusion The application of perioperative chemoradiotherapy should be determined according to the clinicopathological features of patients. Our nomogram provided a reliable tool for screening patients who were right for PCRT and evaluating individual survival benefits.

The aim of this study was to compare: i) the physiological and perceptual responses of low-load exercise [(moderate intensity exercise (MI)] with different levels of blood flow restriction (BFR), and ii) MI with BFR on the bike with high intensity (HI) exercise without BFR. The protocol involved large muscle mass exercise at different levels of BFR, and this differentiates our study from others. Twenty-one moderately trained males (age: 24.6 ± 2.4 years; VO2peak: 47.2 ± 7.0 ml. kg-1.min-1, mean ± sd) performed one maximal graded exercise test and seven 5-min constant-load cycling bouts. Six bouts were at MI [40% peak power (Ppeak), 60%VO2peak], one without BFR and five with different levels of BFR (40%, 50%, 60%, 70%, 80% of estimated arterial occlusion pressure). The HI bout (70%Ppeak, 90%VO2peak) was without BFR. Oxygen uptake (VO2), heart rate (HR), blood lactate (BLa), rate of perceived exertion (RPE), and tissue oxygen saturation (TSI) were recorded. Regardless of pressure, HR, BLa and RPE during MI-BFR were higher compared to MI (p < 0.05, ES: moderate to very large), and TSI reduction was greater in MI-BFR than MI (p < 0.05, ES: moderate to large). The responses of VO2, HR, BLa, RPE and TSI induced by the different levels of BFR in MI-BFR were similar. Regardless of pressure, the responses of VO2, HR, BLa and RPE induced by MI-BFR were lower than HI (p < 0.05), except for TSI. TSI change was similar between MI-BFR and HI. It appears that BFR equal to 40% of arterial occlusion pressure is sufficient to reduce TSI when exercising with a large muscle mass.

Abstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

Abstract Background Since the 1990s, families from the ecologically hostile mountainous southern areas of Ningxia Province, China, have been migrating to the northern areas of the province. This study compared the prevalence of behavioral problems among migrant adolescents to those among host adolescents (adolescents from the northern areas) and adolescents in the region of origin (adolescents from the southern areas), to determine whether ecological migration is related to adolescent behavioral problems, and possible changes in such problems over time. Methods We used the Children and Adolescents Ecological Migration Survey on Mental Health, administered to 4805 students aged 12–16 years and their parents between 2012 and 2014 (W1), of whom 1753 students and their parents completed the follow-up between 2014 and 2017 (W2). Parents answered questions related to adolescent behavioral problems, main source of family income, parents’ desire to reverse migrate, improved standard of living, and parents’ educational attainment, while children completed the Eysenck Personality Questionnaire and a classroom environment questionnaire. Results The prevalence of behavioral problems among the migrant adolescents (28.04%) was significantly higher than among host adolescents (21.59%) or adolescents in the region of origin (24.37%; p

Chloride-Induced Stress Corrosion Cracking (CISCC) has been frequently reported in the petrochemical industries where it usually causes failure to the austenitic stainless steel structures encased with thermal insulation in a chloride-containing environment. This study aims to analyze and evaluate the risk of chloride concentration and different types of insulation materials on CISCC of Austenitic SUS 304L. The experimental study was carried out for 14 days using U-bend specimens through the Drip Test apparatus, as per ASTM G30 and ASTM C692. U-Bend specimens were installed onto the test rig and shielded with different insulation materials. Sodium chloride (NaCl) salt solutions were periodically dripped onto the specimens, to simulate the wet and dry cycle. Insulation materials used were rockwool, calcium silicate and perlite, whereas the concentrations of NaCl solutions were set at 0.1, 1.0 and 3.5 wt.%. The specimens were inspected using dye penetration tests (DPT), stereo microscope and optical microscope throughout the study to determine the CISCC susceptibility. Results showed that cracking was observed on the specimen with rockwool insulation at 3.5 wt% NaCl and 90°C. Rockwool has a high water absorption capacity at which saltwater will evaporate when in contact with a hot metal surface, resulting in the build-up of salt deposits of high concentration over time. SCC was not observed on other specimens with different conditions, but salt deposits, general corrosion and pitting corrosion were found. From the study, the thermal insulation of rockwool was found to have the highest tendency to cause SCC, followed by calcium silicate and perlite.

The benign nature of defects in lead halide perovskites is widely regarded as the basis for their outstanding optoelectronic properties. Here Righetto et al. overthrew this perception, revealing the defects’ surprising potency to hot carriers and devised a strategy to suppress them.

Metadiscourse refers to linguistic items, which functions to establish a connection with imagined readers of a text (Hyland, 2004). The use of metadiscourse has received much attention in various contexts, yet, little works are focusing on disciplinary metadiscourse, that has been carried out. To address this gap, this study explored, described, and compared the use of disciplinary metadiscourse by eight Malaysian first-year ESL doctoral students across four areas of study in education. The study reported in this article focuses on development or changes in writing over time. This study is quantitative in nature with a corpus-based approach utilizing AntConc (3.4.4) to examine the frequency of three dimensions of academic discourse in their writing, namely textual, engagement, and evaluative The results of this analysis show that (i) the engagement dimension (3.1%) was the lowest of all three dimensions in written work, reinforcing the argument that first-year ESL doctoral students are less experienced at using textual metadiscourse resources, and (ii) frequency of all three dimensions of academic discourse in their writing differs across time between first written drafts to the final written drafts. These are first-year ESL doctoral students, who are writing in different fields of educational research. The implication is that teaching and learning of disciplinary metadiscourse should involve explicit explanation, demonstration, and practice of its use, and development in the academic writing process. Academic writing; corpus analysis; ESL doctoral students; metadiscourse

Abstract Background Subacute thyroiditis (SAT) is the most common cause of thyroid pain. Several clinical guidelines recommend that patients who fail to respond to full doses of non-steroidal anti-inflammatory drugs (NSAIDs) should be treated instead with oral corticosteroid therapy. However, albeit strong recommendations, the treatment protocol is based on low-quality evidence and high-quality clinical trials are lacking with respect to the optimal initiation dosage and usage of corticosteroid. We aimed to evaluate whether 15 mg/day of prednisolone (PSL) as the initial dosage could provide non-inferiority effectiveness but with lower risk and more safety compared with 30 mg/day of PSL as the initial dosage. Methods/design This is a multicenter, open-label, randomized, parallel trial that will be conducted at five academic hospitals in China. A total of 90 adult patients diagnosed with SAT who present moderate to severe pain or fail to respond to full doses of NSAIDs will be randomly assigned with a 1:1 ratio to the low initial PSL dosage group (15 mg daily) and standard initial PSL dosage group (30 mg daily). The primary endpoint is the time period (days) required for PSL treatment (including PSL treatment for recurrence). Discussion Our randomized controlled trial will try to determine the optimal protocol in the treatment of SAT by providing high-quality evidence. Trials registration Chinese Clinical Trial Register, ChiCTR1900023884. Registered on 15 June 2019.

Abstract Background The preservation of fertility and integrity of the reproductive organs has increasingly been of concern to most women with adenomyosis. Adenomyomectomy is conservative surgery that is now widely applied; however, relapse is a serious problem after the operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the rate of disease recurrence. However, there is still a lack of evidence from randomized clinical trials examining the efficacy of GnRHa in decreasing the postoperative recurrence rate. Method/design Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse assessed using a visual analogue scale (VRS) and numeric rating scale (NRS), pictorial blood loss assessment chart (PBAC) score, and the size of the uterus and the lesion as measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, adverse events, assessment by the Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels, and anti-Muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, and 36 months after conservative surgery. Discussion The result of this large, multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation. Trial registration Chinese Clinical Trial Registry: ChiCTR1800014340 . Registered on 6 January 2018.

Corticosteroid injections are commonly indicated in inflammatory conditions involving the soft tissues, tendon sheaths, bursae, and joints. Local corticosteroids carry a lower risk of complications than systemic corticosteroid but may be systemically absorbed and subsequently suppress the hypothalamic-pituitary-adrenal (HPA) axis. This can cause secondary adrenal insufficiency (SAI) as well as iatrogenic Cushing’s syndrome. We report a 78-year-old female who presented with nonspecific gastrointestinal symptoms after a recent intra-articular steroid injection in her shoulder. She had hyponatremia, low morning cortisol, and failed to respond to high-dose cosyntropin. Further workup revealed the underlying cause to be SAI. Follow-up testing revealed a recovery of HPA responsiveness within 2 weeks of her initial diagnosis. Conclusion. Our case highlights how the hypothalamic-pituitary axis (HPA) can be suppressed with intra-articular steroids. The threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after steroid injections. Once diagnosed, temporary treatment with steroids may be required.

Background. Adrenal hemorrhage (AH) is a serious endocrine complication of antiphospholipid syndrome (APLS). Case Presentation. We report a 45-year-old man who presented with several deep venous thromboses and was initially treated with apixaban, who later developed bilateral AH. Laboratory findings were consistent with cortisol deficiency yet preserved aldosterone physiology. He was diagnosed with APLS and treated with warfarin. After 8 months of follow-up, he remained on cortisol replacement with no evidence of recovery. We reviewed PubMed/MEDLINE indexed articles from 1950 to 2022 for cases of AH in APLS patients on anticoagulation. Six cases of patients on direct oral anticoagulants (DOACs) were reported. Discussion. The unique vasculature of the adrenal glands creates a “functional vascular dam” in the zona reticularis, which is susceptible to thrombosis in situ and hemorrhage. DOACs may further increase the risk of AH. Conclusion. Depending on the degree of adrenal involvement in AH, patients can present with partial or complete primary adrenal insufficiency. More data are needed to characterize adrenal function after AH, and the safety of DOAC versus warfarin in patients with APLS warrants further studies.

AimDespite a significant improvement in the number of studies on myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorder (MOGAD) over the past few years, MOG-IgG-associated cortical/brainstem encephalitis remains a relatively uncommon and less-reported presentation among the MOGAD spectrum. This study aimed to report the clinical course, imaging features, and therapeutic response of MOG-IgG-associated cortical/brainstem encephalitis.MethodsData of four patients who suffered from cortical encephalitis with epileptic seizures and/or brainstem encephalitis during the course of the disease were retrospectively collected and analyzed.ResultsIn this study, three male patients and one female patient, with a median age of onset of 21 years (ranging 20–51 years) were enrolled. An epileptic seizure was the main symptom of cortical encephalitis in these patients, while the manifestations of brainstem encephalitis were diverse. Cranial MRI demonstrated abnormal signals in unilateral or bilateral cortical or brainstem. Cerebrospinal fluid studies showed normal or mildly elevated leukocyte counts and protein levels, and a cell-based assay detected positive MOG-IgG in the serum of all patients. Two patients were misdiagnosed at the first attack, and both experienced a relapse. All of them accepted the first-line immunotherapy after a confirmed diagnosis and had a good outcome.ConclusionEarly suspicion of MOG-IgG-associated encephalitis is necessary for any patient with sudden onset of seizures or symptoms of brainstem damage, especially with lesions on unilateral/bilateral cortical or brainstem on brain MRI.