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Seasonal climate forecasts have socioeconomic value, and the quality of the forecasts is important to various societal applications. Here we evaluate seasonal forecasts of three climate variables, vapor pressure deficit (VPD), temperature, and precipitation, from operational dynamical models over the major cropland areas of South America; analyze their predictability from global and local circulation patterns, such as El Niño–Southern Oscillation (ENSO); and attribute the source of prediction errors. We show that the European Centre for Medium-Range Weather Forecasts (ECMWF) model has the highest quality among the models evaluated. Forecasts of VPD and temperature have better agreement with observations (average Pearson correlation of 0.65 and 0.70, respectively, among all months for 1-month-lead predictions from the ECMWF) than those of precipitation (0.40). Forecasts degrade with increasing lead times, and the degradation is due to the following reasons: 1) the failure of capturing local circulation patterns and capturing the linkages between the patterns and local climate; and 2) the overestimation of ENSO’s influence on regions not affected by ENSO. For regions affected by ENSO, forecasts of the three climate variables as well as their extremes are well predicted up to 6 months ahead, providing valuable lead time for risk preparedness and management. The results provide useful information for further development of dynamical models and for those who use seasonal climate forecasts for planning and management. Significance Statement Seasonal climate forecasts have socioeconomic value, and the quality of the forecasts is important to their applications. This study evaluated the quality of monthly forecasts of three important climate variables that are critical to agricultural management, risk assessment, and natural hazards warning. The findings provide useful information for those who use seasonal climate forecasts for planning and management. This study also analyzed the predictability of the climate variables and the attribution of prediction errors and thus provides insights for understanding models’ varying performance and for future improvement of seasonal climate forecasts from dynamical models.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease of hematopoietic stem cells (HSCs). Long noncoding RNAs (lncRNAs) perform a wide range of biological functions, including the regulation of gene expression, cell differentiation, and proliferation, but their role in PNH remains unclear.CD59− and CD59+ granulocytes and monocytes from 35 PNH patients were sorted. High-throughput sequencing was analyzed in 5 PNH patients, and differentially expressed lncRNAs and mRNAs were identified. The mRNAs with fragments per kilobase of exon model per million mapped fragments (FPKM) > 10 in at least 3 patients were selected, and experiments were performed to identify their upstream regulatory lncRNAs. The expression of selected mRNAs and lncRNAs was verified by qRT‒PCR, and the correlation of these expression patterns with clinical data from other 30 PNH patients was analyzed. Then, the functions of the lncRNAs were studied in the PIGA-KO-THP-1 cell line.Transcription analysis revealed 742 upregulated and 1376 downregulated lncRNAs and 3276 upregulated and 213 downregulated mRNAs. After deep screening, 8 highly expressed mRNAs that were related to the NF-κB pathway were analyzed to determine coexpression patterns. LINC01002, FAM157C, CTD-2530H12.2, XLOC-064331 and XLOC-106677 were correlated with the 8 mRNAs. After measuring the expression of these molecules in 30 PNH patients by qRT‒PCR, lncRNA FAM157C was verified to be upregulated in the PNH clone, and its expression levels were positively correlated with the LDH levels and CD59− granulated and monocyte cell ratios. After knockdown of the FAM157C gene in the PIGA-KO-THP-1 cell line, we found that the cells were arrested in the G0/G1 phase and S phase, the apoptosis rate increased, and the cell proliferation decreased.LncRNA FAM157C was proven to promote PNH clone proliferation, and this is the first study to explore the role of lncRNAs in PNH.

In view of the fact that the contact between the pad and the disc cannot match perfectly in the actual braking process, the influence of contacting shape on the tribological performance was studied. Four copper-based brake pads in ratio (radial dimension / circumferential dimension) of 0.4, 0.6, 0.8 and 1.2 were used to perform contacting shape test on a small-scaled braking dynamometer at speeds 60 km/h, 100 km/h, 140 km/h and 180 km/h and contact pressure 0.5 MPa. The results indicated that contacting shape caused the difference of temperature of the brake system, which affected the friction performance. The peak temperature of the disc decreased from 331°C to 293.2°C with ratio increasing, and the maximum effective stress of the disc decreased 15%. In ratio of 0.4, the higher friction temperature and effective stress made the friction surface easy to plough, so the friction coefficient was low and the wear was nonuniform. In ratio of 1.2, the wear particles accumulated, resulting in high friction coefficient and uniform wear.

A new gold(i) self-relay catalysis reaction enabling the annulative oxygenation of propargylic alcohols with various O-nucleophiles, such as carboxylic acids, alcohols and TBHP, is reported, producing a series of functionalized benzofurans.

Anthropogenically forced-warming and La Niña forced-precipitation deficits caused at least a sixfold risk increase for compound extreme low precipitation and high temperature in California–Nevada from October 2020 to September 2021.

In response to the shortcomings of the dark channel prior and optimization methods in window selection and object depth variation, this paper proposes a visibility detection algorithm based on object region selection. The algorithm introduces superpixel segmentation to divide the image into superpixel blocks and extracts the superpixel blocks containing the target object for visibility calculation. In the visibility calculation, the dark channel and transmission rate extraction can be obtained only from the target object region, without the need to process the entire image region. This improves the accuracy of the target object parameter calculation and speeds up the computation.

The gut microbiome and its metabolism may provide crucial insight into the cause of iron deficiency anemia (IDA) in pregnant women. This study aimed to investigate the effect of the gut microbiome and its related metabolites on pregnant women with iron deficiency (ID) and IDA. Maternal cubital venous blood and stool samples were collected from healthy control pregnant women (HC, non-anemic, n=10), pregnant women with ID non-anemia (ID, n=10), and IDA (n=10). All groups were subjected to fecal metagenomics and metabolomics. The composition and function of the gut microbiome were then compared in pregnant women with ID and IDA with HC after excluding the possibility of inflammation and insufficient iron absorption capacity. Whole-genome shotgun libraries were prepared by quantifying metagenomic DNA samples with Quant-iT PicoGreen dsDNA Assay. The levels of 41 microbial species, including 21 Streptococci and ten metabolites (catechol), which could serve as siderophores, were increased. In contrast, 3 Bacteroides and six metabolites were decreased in pregnant women with IDA (p

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS.

Purpose This study aims to clarify the relationship of friction material type and brake disc temperature through braking experiment. Design/methodology/approach The braking performances of resin materials (RM), semimetallic materials (SM) and copper-based powder metallurgy materials (PM) friction blocks mating with forged steel brake disc were examined based on TM-I-type reduced-scale inertial braking dynamometer. The brake disc surface temperature was recorded by infrared thermal camera during braking. Findings Experimental results indicate that the thermal wear resistance of three friction materials differs with mental content, resulting in the deviation of pad-disc system contact state during braking, thus forming different temperature distribution on the brake disc surface. The peak temperature on the disc face of RM (190°C) is 36.6% and 45.4% lower than that of PM (300°C) and SM (348°C) at 160 km/h. The maximum radial temperature deviation of PM (35°C) is approximately three times than that of RM (12°C) and 40% higher than that of SM (25°C) at 50 km/h, whereas the maximum temperature deviation of SM (97°C) is six times than that of RM (16°C) and 31% higher than that of PM (74°C) at 160 km/h. Originality/value The effect of friction material type on the disc surface temperature distribution is revealed, which provides a meaningful reference for the design of brake friction pairs and choice of brake pad materials.

To improve the teaching practice effect of clothing major, this study applies the practical clothing design method to the teaching of clothing major to analyze the digital clothing design and establishes a convex quadratic conic programming model for a class of force optimization problems. Then, this study transforms the optimality condition of the problem into a new projection equation system, constructs a suitable constant coefficient matrix according to the characteristics of the equation system, and obtains an equivalent linear equation system. In addition, this study proposes a full Newton step projection algorithm to directly solve the convex quadratic conic programming. Through the results of the experimental research, it can be seen that the practical clothing design method has a good application in the teaching of clothing majors, and it can be applied in the practice of clothing teaching.

Background Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2 nd generation oral proteasome inhibitor (PI), has been approved for MT because of the convenience and tolerability. Aims We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimens in NDMM patients. Methods This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry since September 2019. After 4 cycles of front-line induction therapy, patients who reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start maintenance therapy. Patients did not reach PR would switch to a 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1-21 of a 28-day cycle. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was PFS from MT. Results A total of 149 patients were enrolled, including 54 in I-MT, 65 in L-MT and 30 in IL-MT. The demographic and clinical characteristics were comparable among three groups at baseline (Table 1), including gender ratio, age, paraprotein isotype, ISS, R-ISS, response status before MT, and ASCT rate. The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were comparable. The median follow-up duration since MT was 6.1, 11.1, and 5.9 months in I-MT, L-MT and IL-MT group, respectively. Disease progression developed in 9.3%, 12.3% and 10% (N=5, 8, 3, respectively) patients. The median PFS was not reached (NR) in all groups. Only one death occurred in I-MT group. There were 84%, 72.3% and 83.3% of the patients reached very good partial response (VGPR) or better before MT, while the best response rates rose to 93%, 82.3% and 90% during maintenance. The prevalence of peripheral neuropathy was 18.5% on I-MT, 10.8% on L-MT and 30% on IL-MT. Grade 2 PN occurred in 3, 1, and 0 patients, respectively. The incidence of gastrointestinal events was 11.1%, 1.5% and 20%, respectively. Grade 3-4 hematologic toxicities was 3.7%, 4.6%, and 3.3%. Infection rates were 7.4%, 6.2% and 3.3%. Skin rashes were more common in lenalidomide containing regimens (3.7%, 7.3% and 6.7%). No drug withdrawal was related to adverse events. Conclusions Due to inadequate access to melphalan and low rate of ASCT in China, there is still a gap of PFS in NDMM patients with those in western countries. We herein design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint--PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable. Figure 1. Baseline Characteristics in three groups. Abbreviations: ISS: international staging system; R-ISS: revised-ISS; HRCAs: high risk cytogenetic abnormalities. sCR: stringent complete remission. CR: complete remission. VGPR: very good partial remission. PR: partial remission. * p ＜ 0.05. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

As a supplement to traditional teaching methods, computer-assisted teaching methods can reflect modern educational concepts, such as creating student-led, teacher-led environments. The goal of college English education is to enable them to communicate effectively in English in their future academic, work, and social interactions, while also developing students’ self-learning skills. Chinese society improves overall cultural competence and adapts to the needs of international communication. Self-directed learning is not static and will increase or decrease with time, discipline, and conditions and is an evolving process. Understanding learning, taking responsibility for one’s own learning, and learning how to learn are all beneficial. Students abound in school life and even throughout their lives. In this paper, we try to propose a computer-based method for constructing an independent English learning model based on a practical study of computer network technology for the development of self-learning ability of non-English majors in a university. This paper uses comparative analysis techniques to compare traditional paper-and-pencil examinations and computer-based online evaluations and analyzes the effects of each. The survey showed that 81% of the students preferred the computer-based assessment. Therefore, the focus of this research is to strengthen the oral English training in college and create an authentic English learning environment for students to really feel the standard English pronunciation, intonation, and knowledge of grammar, listening, reading, writing, and translation.

Abstract: Aplastic anemia (AA) is a hematological disease characterized by pancytopenia and hypofunctional bone marrow hematopoiesis. Patients with AA are treated with either immunosuppressive therapy (IST) using anti-thymocyte globulin (ATG) and cyclosporine (CsA) or hematopoietic stem cell transplantation (HSCT), if a matched donor is available. The standard IST regimen for AA patients results in response rates up to 70% and even higher overall survival. However, primary and secondary failures after IST remain frequent, and to date, all attempts aiming to overcome this problem have been unfruitful. The nontransplant therapeutic options for AA have significantly expanded during the last few years. Here, we review the new trends of nontransplant therapy for AA and summarize the current therapeutic effect of AA.

Among the newly diagnosed cancers in women, breast cancer metastasis is a key factor contributing to the poor prognosis. BMSCs are critical components for the malignant microenvironment. Studies have shown that the interaction between tumor cells and BMSCs support breast cancer progression. However, BMSCs’ effect on breast cancer cells is not yet clear. BMSCs and breast cancer cell MCF-7 were co-cultured to analyze tumor cell proliferation and apoptosis along with analysis of E-cadherin and Vimentin expression by real-time PCR, interleukin-6 and matrix protease-2 and PTEN12 expression. Co-culture of BMSCs promoted breast cancer cell proliferation, decreased apoptosis-related Caspase 3 activity and downregulated the expression of EMT related factors, upregulated IL-6 secretion and MMP-2, and downregulated PTEN12 expression (P < 0.05). In conclusion, BMSCs can promote breast cancer cell proliferation and survival and affect breast cancer transformation possibly through inhibiting the expression of PTEN12.

The suppression of osteoblast (OB) activity is partially responsible for multiple myeloma (MM) bone disease. Long non-coding RNAs (lncRNAs) play a vital role in bone formation and resorption. However, their functions in OBs from patients with MM have rarely been reported. Through high-throughput sequencing of OBs from patients with MM and healthy controls, we identified several lncRNAs and messenger RNAs (mRNAs) with different expression profile and validated them using quantitative real-time PCR. In total, 22 upregulated and 21 downregulated lncRNAs were found in OBs from patients with MM. Moreover, 18 upregulated protein-coding mRNAs were identified. The expression levels of LINC01473 and its associated co-expression mRNA, CD74, were higher in patients with MM than in healthy controls (p=0.047 and p=0.016, respectively). LINC01473 expression demonstrated a negative correlation with serum interleukin-2 and tumor necrosis factor α levels, whereas the expression of mRNA CD74 was positively associated with serum lactic dehydrogenase in patients with MM. Aberrant expression of lncRNAs and mRNAs was observed in OBs from patients with MM. This study identifies new promising targets for further research on imbalanced bone formation and resorption and MM immune escape.

Tumor-associated macrophages (TAMs) are originated from circulating mononuclear cells in peripheral blood. They result from the recruitment of tumor cells and are a vital constituent of the tumor microenvironment. TAMs may be involved in the immunological escape of vicious clonal plasma cells (PC) in the bone marrow (BM) of sufferers with myeloma.From March 2020 to January 2021, 28 healthy controls (HC) and 86 multiple myeloma (MM) (53 newly diagnosed MM [NDMM] and 33 remissions) patients were enrolled as objects of the study. The expression of TAMs in the BM, CSF1 on CD138 + cells, and CSF1R on macrophages were detected by the method of flow cytometry, and the expression of PD-1 on CD8 + T cells and PD-L1 on TAMs were also done. Bone marrow mononuclear cells (BMMNCs) were extracted and cultured into TAMs, CD8 + T cells were sorted by magnetic beads and cultured, a coculture system was established and different inhibitors were added. The expression of the perforin and granzyme B was detected by flow cytometry.The percentage of TAMs in NDMM group (61.49 ± 2.176%) increased when compared with remission (23.08 ± 1.699%, p 0.001) and HC group (17.95 ± 1.865%, p 0.001), and TAMs decreased after adding CSF1R inhibitor. Moreover, the expression of CSF1 on CD138 + cells increased significantly in NDMM group (17.090 ± 0.9156%) than remission (8.214 ± 0.5911% p 0.001), and HC group (5.257 ± 0.6231%, p 0.001), and CSF1R on macrophages increased significantly in NDMM group (58.78 ± 2.286%) than remission (20.74 ± 1.376%, p 0.001) and HC group (17.42 ± 1.081%, p 0.001). The expression of PD-1 on CD8 + T cells in NDMM group (32.64 ± 2.982%) increased than remission (20.35 ± 2.335% p 0.01) and HC group (17.53 ± 1.349%, p 0.001), and PD-L1 on TAMs also increased in NDMM group (50.92 ± 2.554%) than remission (20.02 ± 1.893%, p 0.001) and HC group (13.08 ± 1.289%, p 0.001). When CD8 + T cells were cocultured with TAMs, the perforin and granzyme B levels decreased significantly. However, the perforin and granzyme B levels were partly restored after adding CSF1R inhibitor and anti-PD-L1 antibody.Our study shows that TAMs were increased in MM patients which can inhibit the function of cytotoxic T lymphocyte (CTL) through the PD-1/ PD-L1 signaling pathway and participate in the occurrence of immune escape of myeloma cells.

Myelodysplastic syndromes (MDS) are clonal malignancies of multipotent hematopoietic stem cells, characterized by ineffective hematopoiesis leading to cytopenia. Hypomethylating agents, including azacitidine, have been used for treating MDS with some success; however, the overall survival rate remains poor and, therefore, finding new therapies is necessary. Selinexor, which exerts anticancer effects against some hematologic tumors, is a nuclear export protein inhibitor that blocks cell proliferation and induces apoptosis in various cancer cell lines. We investigated the effects of combined selinexor and azacitidine administration on two MDS cell lines, namely SKM-1 and MUTZ-1. Cells were subjected to a proliferation assay, and the effects of each drug alone, and in combination, were compared. Changes in apoptosis and the cell cycle between groups were also analyzed. Western blotting was conducted to identify the underlying mechanism of action of combined selinexor and azacitidine therapy. The results revealed that the combination of selinexor and azacitidine synergistically inhibited MDS cell proliferation and arrested the cell cycle at the G2/M phase. This combination also promoted MDS cell apoptosis and enhanced p53 accumulation in the nucleus, thereby allowing p53 to be activated and to function as a tumor suppressor. Overall, our results indicate that the combination of selinexor and azacitidine may be a promising approach for treating MDS.

Severe aplastic anemia (SAA) is an immune-mediated bone marrow failure characterized by pancytopenia. This study was aimed at uncovering proteins of plasma that were differentially expressed in SAA patients. 8 SAA patients and 8 health controls were enrolled and detected by data independent acquisition (DIA) technology. 154 differential expression proteins (DEPs) in plasma of SAA patients were identified. GO and KEGG analyses indicated DEPs were mainly involved in the immune system process. Specifically, C-C motif chemokine 18 (CCL18), matrix metalloproteinase-3 (MMP3), histidine-rich glycoprotein (HRG), and lactotransferrin (lactoferrin (Lf)) may play an important role in the immune pathogenesis of SAA. CCL18, MMP3, HRG, and Lf might be potential biomarkers for SAA.

The 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16-26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9-19 years and 27-45 years with Chinese females aged 20-26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9-19 years.Participants aged 9-45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded.In total, 1990 participants (690 aged 9-19 years; 650 aged 20-26 years; 650 aged 27-45 years) were enrolled. At 1 month post-Dose 3,99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9-19-year age group were non-inferior to those in participants aged 20-26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27-45-year age group were non-inferior to those in participants aged 20-26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9-19, 20-26, and 27-45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths.Antibody responses induced by 9vHPV vaccination in Chinese females aged 9-19 years and 27-45 years were non-inferior to those in Chinese females aged 20-26 years. The vaccine was generally well tolerated.gov Identifier: NCT03903562.

This study examined the impact of intergenerational socioeconomic mobility on the risk of cognitive impairment in a cohort of Chinese older adults aged 60 years and older. Data were derived from the 2014 wave of the Chinese Longitudinal Healthy Longevity Survey. Logistic regression models were performed to assess the impact of three dimensions of socioeconomic mobility (occupational mobility, educational mobility, and residential mobility) on the risk of cognitive impairment. We found that men who were stable with non-professional jobs across generations had a higher risk of cognitive impairment than their counterparts who experienced upward occupational mobility compared to their father. This pattern was not observed in women. There was little evidence that educational mobility or residential mobility affected cognitive impairment in later life. The findings have implications for advancing supportive policies and practices related to maximizing the benefits of education and career advancements for cognition in later life.

A facile and sustainable approach for the amination of benzothiazoles with KSeCN using iodine as the catalyst in water has been disclosed under transition-metal free conditions. The reaction proceeded smoothly to afford various primary 2-amino benzothiazoles in up to 96% yield. A series of control experiments were performed, suggesting a ring-opening mechanism was involved via a radical process. This protocol provides efficient synthesis of primary 2-aminobenzothiazoles

The induction of cellular senescence is considered as a potent strategy to suppress cancer progression. Cucurbitacin E (CE) belongs to the triterpenoids and has received substantial attention for its antineoplastic property. However, the function of CE on cellular senescence remained elusive. Herein, we revealed that CE significantly induced cellular senescence in colorectal cancer (CRC) cells. The CE effects on the cellular senescence in CRC cells were confirmed by observing the common features of the senescence, such as the enhanced activity of senescence-associated β-galactosidase, γ-H2AX positive staining, and upregulation of senescence-associated proteins including p53, p27, and p21. Moreover, CE exerted pro-senescent effects in CRC cells via attenuating the transcription factor activating enhancer-binding protein 4 (TFAP4) expression, and the ectopic expression of TFAP4 blocked the CE-induced senescence. Mechanistically, CE treatment caused a robust increase in miR-371b-5p, which markedly repressed TFAP4. In contrast, silencing of miR-371b-5p counteracted the percentages of CE-induced senescent cells from 37.49 ± 2.61 to 7.06 ± 0.91% in HCT-116 cells via derepressing TFAP4 to attenuate the expression of p53, p21, and p16. Altogether, these results demonstrated that dietary CE induces CRC cellular senescence via modulating the miR-371b-5p/TFAP4 axis and presents opportunities for potential therapeutic strategies against CRC.