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In China, exploring the relationship between human capital and green economy in the context of economic transformation can promote the construction of an ecological civilization and high-quality economic development. This paper is dedicated to assessing the impact of human capital stock, human capital structure, and the difference between the two on China's green economy. Using the super-efficiency slack-based measure (SBM) model, this paper evaluated the green total factor productivity (GTFP) of 30 Chinese provinces to assess the greenness of its economy and analyzed its spatiotemporal evolution from 2000 to 2017. A spatial error model (SEM) was established to explore the impact of human capital on green economy. The results show that (1) the GTFP of China increased continuously from 0.219 to 0.457, showing a regional spatial differentiation of "eastern regioncentral regionwestern region." The spatial gaps of the green economy in the east-west and north-south directions are narrowing. (2) Moran's I index and Moran's I scatter plot indicate a significant spatial correlation between human capital and China's green economy. The local spatial correlation between human capital and green economy is mainly characterized by "high-high" and "low-low" types of agglomeration. (3) The effects of human capital stock and human capital structure on green economy were both positive, with coefficients of 0.0005 and 0.1601, respectively, but the effects of human capital structure were not significant. (4) The results of regional regression show that the difference between the human capital impact coefficients on green economy in the eastern and midwestern regions is small. The impact of human capital stock and human capital structure on green economy is consistent with the national level results. It can be preliminarily concluded that the development of China's green economy relied more on improving the human capital stock than on the improvement of the human capital structure. This study further enriches the literature on the green economy and provides information that can support government policy-making.

In-memory computing provides an opportunity to meet the growing demands of large data-driven applications such as machine learning, by colocating logic operations and data storage. Despite being regarded as the ultimate solution for high-density integration and low-power manipulation, the use of spin or electric dipole at the single-molecule level to realize in-memory logic functions has yet to be realized at room temperature, due to their random orientation. Here, we demonstrate logic-in-memory operations, based on single electric dipole flipping in a two-terminal single-metallofullerene (Sc2C2@Cs(hept)-C88) device at room temperature. By applying a low voltage of ±0.8 V to the single-metallofullerene junction, we found that the digital information recorded among the different dipole states could be reversibly encoded in situ and stored. As a consequence, 14 types of Boolean logic operation were shown from a single-metallofullerene device. Density functional theory calculations reveal that the non-volatile memory behaviour comes from dipole reorientation of the [Sc2C2] group in the fullerene cage. This proof-of-concept represents a major step towards room-temperature electrically manipulated, low-power, two-terminal in-memory logic devices and a direction for in-memory computing using nanoelectronic devices.

Background Multimorbidity of non-communicable diseases (NCDs) is increasingly prevalent among older adults around the world, leading a higher risk of household catastrophic health expenditure (CHE). As current powerful evidence was insufficient, we aimed to estimate the association between multimorbidity of NCDs and the risk of CHE in China. Methods We designed a cohort study using data investigated in 2011–2018 from the China Health and Retirement Longitudinal Study, which is a nationally-representative study covering 150 counties of 28 provinces in China. We used mean ± standard deviation (SD) and frequencies and percentages to describe baseline characteristics. Person χ2 test was employed to compare the differences of baseline characteristics between households with and without multimorbidity. Lorenz curve and concentration index were used to measure the socioeconomic inequalities of CHE incidence. Cox proportional hazards models were applied to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between multimorbidity and CHE. Results Among 17,708 participants, 17,182 individuals were included for the descriptive analysis of the prevalence of multimorbidity in 2011, and 13,299 individuals (8029 households) met inclusion criteria and were included in the final analysis with a median of 83 (interquartile range: 25–84) person-months of follow-up. 45.1% (7752/17,182) individuals and 56.9% (4571/8029) households had multimorbidity at baseline. Participants with higher family economic level (aOR = 0.91, 95% CI: 0.86–0.97) had lower multimorbidity prevalence than those with lowest family economic level. 82.1% of participants with multimorbidity did not make use of outpatient care. The CHE incidence was more concentrated among participants with higher socioeconomic status (SES) with a concentration index of 0.059. The risk of CHE was 19% (aHR = 1.19, 95% CI: 1.16–1.22) higher for each additional NCD. Conclusions Approximately half of middle-aged and older adults in China had multimorbidity, causing a 19% higher risk of CHE for each additional NCD. Early interventions for preventing multimorbidity among people with low SES could be intensified to protect older adults from financial hardship. In addition, concerted efforts are needed to increase patients’ rational healthcare utilization and strengthen current medical security for people with high SES to reduce economic disparities in CHE.

Effective protection against X-ray is the premise of utilizing the X-ray, thus it is critical to develop novel X-ray shielding materials with both low density and high X-ray attenuation efficiency. As the even distribution of high-Z element components is of great significance for increasing the attenuation efficiency of X-ray shielding materials, in this study, the microfiber membrane (MFM), a type of synthetic leather featuring hierarchical structure was chosen to provide large surface area for the dispersion of rare earth (RE) element. Meanwhile, plant polyphenol was utilized to achieve the stable loading and uniform dispersion of the Ce or Er into MFM. Benefiting from the assistance of polyphenol and hierarchical structure of MFM, the even dispersion of RE element was successfully realized. The resultant shielding materials displayed approximately 10% superior X-ray attenuation efficiency compared to that without polyphenol, and an averagely 9% increment in X-ray attenuation efficiency than that without hierarchical structure. Moreover, the obtained composite with a thickness of 2.8 mm displayed superior X-ray shielding performance compared to 0.25 mm lead sheet in 16–83 keV and retained an ultralow density of 1.4 g cm–3. Our research results would shed new light on the manufacture of high-performance X-ray shielding materials with excellent X-ray shielding performance. Graphical Abstract

Genetic analysis revealed that CmCLV3 is a candidate gene for the variation in melon carpel number. Carpel number (CN) is an important trait in melon. Three-CN melon fruit is oval, while 5-CN melon fruit has a round or flat shape. Herein, a genetic analysis of a population in which the CN locus was segregated indicated that 3-CN is controlled by a major dominant effective gene. Bulked segregant analysis and initial linkage mapping placed the CN locus in a 6.67 Mb region on chromosome 12, and it was narrowed to 882.19 kb with molecular markers and recombinant plants. Fine mapping with a large F

Fiberoptic bronchoscopy is a complex procedure with the need for sufficient patient anesthesia/sedation while maintaining safety. This trial aimed to evaluate the efficacy, safety, and pharmacokinetics of HSK3486 during fiberoptic bronchoscopy.This multicenter, double-blind, randomized, non-inferiority, parallel-group phase 3 trial was conducted in patients who underwent fiberoptic bronchoscopy. Patients randomly received HSK3486 0.4 mg/kg (N = 134) or propofol 2.0 mg/kg (N = 133). The primary efficacy endpoint was the successful rate of fiberoptic bronchoscopy, and secondary efficacy endpoints included successful induction of anesthesia/sedation, duration, time to being fully alert, and time to patient discharge. Safety assessments and drug concentrations were also measured.A total of 267 patients completed fiberoptic bronchoscopy, with a success rate of 100% and a 95% confidence interval of - 2.8 to 2.8% for the difference between the groups, which met the predesigned criteria of - 8%, confirming the non-inferiority of anesthesia/sedation produced by HSK3486 compared to propofol. Among the secondary efficacy endpoints, only time to full alertness (median 8.50 vs. 6.00 min, P = 0.012) and time to discharge (median 13.00 vs. 9.87 min, P = 0.002) were slightly longer in the HSK3486 group. The incidence of adverse events was significant lower in the HSK3486 group (52.6 vs. 76.5%, P0.001) mainly because of less pain on injection (4.4 vs. 39.4%, P0.001) compared to the propofol group. HSK3486 had a similar terminal elimination half-life as propofol.HSK3486 exhibited non-inferiority anesthesia/sedation compared to propofol in patients undergoing fiberoptic bronchoscopy, and had a good safety profile with a lower incidence of pain on injection.Clinicaltrials.gov, NCT04111159, registered on 1 October 2019.

Vibrio parahaemolyticus is a waterborne pathogen that can cause acute gastroenteritis, wound infection, and septicemia in humans. The molecular basis of its pathogenicity is not yet fully understood. Phages are found most abundantly in aquatic environments and play a critical role in horizontal gene transfer. Nevertheless, current literature on biological roles of prophage-encoded genes remaining in V. parahaemolyticus is rare. In this study, we characterized one such gene VpaChn25_0734 (543-bp) in V. parahaemolyticus CHN25 genome. A deletion mutant ΔVpaChn25_0734 (543-bp) was obtained by homologous recombination, and a revertant ΔVpaChn25_0734-com (543-bp) was also constructed. The ΔVpaChn25_0734 (543-bp) mutant was defective in growth and swimming mobility particularly at lower temperatures and/or pH 7.0–8.5. Cell surface hydrophobicity and biofilm formation were significantly decreased in the ΔVpaChn25_0734 (543-bp) mutant (p VpaChn25_0734 (543-bp) gene significantly reduced the cytotoxicity of V. parahaemolyticus CHN25 to human intestinal epithelial cells (p ΔVpaChn25_0734 (543-bp) mutant, showing down-regulated carbon source transport and utilization, biofilm formation, and type II secretion system (p VpaChn25_0734 (543-bp) enhanced V. parahaemolyticus CHN25 fitness for survival in the environment and the host. The results in this study facilitate better understanding of pathogenesis and genome evolution of V. parahaemolyticus, the leading sea foodborne pathogen worldwide.

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies—YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.

Background Given the crucial role of gut microbiota in animal and human health, studies on modulating the intestinal microbiome for therapeutic purposes have grasped a significant attention, of which the role of fecal microbiota transplantation (FMT) has been emphasized. Methods In the current study, we evaluated the effect of FMT on gut functions in Escherichia coli (E. coli) infection by using mice model. Moreover, we also investigated the subsequently dependent variables of infection, i.e., body weight, mortality, intestinal histopathology, and the expression changes in tight junction proteins (TJPs). Results The FMT effectively decreased weight loss and mortality to a certain extent with the restoration of intestinal villi that resulted in high histological scores for jejunum tissue damage (p Escherichia-Shigella, Sphingomonas, Collinsella, etc., were significantly increased, whereas beneficial bacteria, belonging to phylum Firmicutes, family Lactobacillaceae, genus Lactobacillus were decreased in the gut of infected mice. Furthermore, we sought to investigate the association of clinical symptoms with FMT treatment with modulation in gut microbiota. According to beta diversity, the microbial community of gut microbiota results reflected the similarities between non-infected and FMT groups. The improvement of the intestinal microbiota in FMT group was characterized by the significant high level of beneficial microorganisms with the synergistic decrease of Escherichia-Shigella, Acinetobacter, and other taxa. Conclusion The findings suggest a beneficial host-microbiome correlation following fecal microbiota transplanatation for controlling gut infections and pathogens-associated diseases.

The SPL gene is a plant-specific transcription factor involved in the regulation of plant growth and development, which have been identified in woody plants. The process of floral bud differentiation affects the timing of flowering and fruit set and regulates plant growth, however, the mechanism of regulation of flower development by SPL genes is less studied. In this study, 56 VcSPL genes were identified in the tetraploid blueberry. The VcSPL gene family was classified into six subfamilies, and analysis of cis-elements showed that VcSPL genes were regulated by light, phytohormones (abscisic acid, MeJA), and low temperature. In the evolutionary analysis, segmental replication may play an important role in VcSPL gene amplification. Interestingly, we also studied diploid blueberry (Bilberry), in which 24 SPL genes were identified, and 36 homologous pairs were found, suggesting a high degree of convergence in the syntenic relationship between blueberry (Vaccinium corymbosum L) and bilberry (Vaccinium darrowii). Based on the expression profile, VcSPL genes were expressed at high levels in flowers, shoots, and roots, indicating a diversity of gene functions. Then we selected 20 differentially-expressed SPL genes to further investigate the role of VcSPL in floral induction and initiation. It showed that the genes VcSPL40, VcSPL35, VcSPL45, and VcSPL53 may play a crucial role in the blueberry floral transition phase (from vegetative growth to flower initiation). These results provided important information for understanding and exploring the role of VcSPLs in flower morphogenesis and plant growth.

Aim Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. Subjects and method In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. Results The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. Conclusion The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Uniform designs have been widely used in physical and computer experiments due to their robust performances. The level permutation method can efficiently construct uniform designs with both lower discrepancy and less aberration. However, the related existing literature has mostly discussed uniform fixed-level designs, the construction of uniform mixed-level designs has been quite few studied. In this paper, a novel level permutation method for constructing uniform mixed-level designs is proposed. Our main idea is to perform level permutations on a new class of designs, called minimum average discrepancy designs, rather than generalized minimum aberration designs as in the fixed-level case. Several theoretical results on the design optimality and construction are obtained. Numerical results suggest the good performance of the resulting designs under various popular discrepancies.

A total of 5195 electromagnetic particle detectors (EDs) are used in the 1-square-kilometer extensive air shower array (KM2A), which is a subarray of the Large High Altitude Air Shower Observatory (LHAASO). As the detection sensitive medium of the EDs, more than 20,000 plastic scintillator units (BC-408), produced by Saint-Gobain, are used in LHAASO. It is important to monitor the light output of the scintillator units among the units. To improve the efficiency, a sampling inspection scheme (misjudgment rate of less than 5%) was designed, and a batch test system was developed. Ten units of scintillator units can be measured at a time. The test system selects the single muon events of cosmic rays to measure the light output values of the plastic scintillator units. The measurement has an uncertainty of less than 2%. By pretest calibration, the difference between different channels can be eliminated. The calibration was implemented approximately every 3 months, and the test system had been running stably for 28 months. By measuring the ratio of the signals of selected far and near probe events, the changes in the quality of different batches of plastic scintillator units can be demonstrated. The test system realized accurate measurement of the light output, and all batches satisfied the requirements of the experiment.

Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of CD4 + T cells with opposite effects which play a crucial role in the pathogenesis of lung injury. In this study, we aim to investigate the protective effect of Pseudomonas aeruginosa outer membrane vesicles (OMVs) preconditioning on lung ischemia–reperfusion (I/R) injury and potential mechanisms. Pathogen-free C57BL/6 mice were randomly divided into four groups: control, Control + OMVs, I/R and I/R + OMVs groups. Bronchoalveolar lavage fluid (BALF), serum, and lung tissues were collected and analyzed for pathophysiology and immune mechanism. OMVs not only attenuated tissue injury and respiratory physiologic function but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration. The numbers of total cells, macrophages, neutrophils, and lymphocytes were markedly decreased in the I/R mice following OMVs preconditioning. OMVs also decreased inflammatory cytokines associated with CD4 + T cells in both BALF and serum. In addition, the level of Tregs and its transcription factor forkhead box P3 (Foxp3) were significantly increased, while the level of Th17 cells and its transcription factor retinoid-related orphan receptor γ (RORγt) were significantly decreased following OMVs preconditioning. In the process of exploring the underlying protection mechanisms of OMVs, we found that OMVs preconditioning significantly reduced protein expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation factor 88 (MyD88) and Phosphorylated nuclear factor kappa B (p-NF-κB), but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). These results suggest that OMVs preconditioning may ameliorate lung I/R injury by regulating the balance of Tregs and Th17 cells through Tim-3 and TLR4/NF-κB pathway.

A series of novel zinc-polyurethane copolymers, which contained zinc cations in the form of polymeric salt and can be exchanged with the sodium ions in sea water, was prepared. As the ion exchange reaction proceeded, the zinc-polyurethane copolymers became soluble and leached out by the flow of sea water. The self-polishing rates of marine antifouling coatings formulated with the polymers proved to be easily controlled by the amount of 2,2-bis(hydroxymethyl) propionic acid. Marine field test revealed that zinc-polyurethane antifouling coatings had excellent efficiency in preventing marine biofouling for more than 12 months. These results proved that the zinc-polyurethane copolymers were a good candidate for the preparation of long-efficiency and controllable marine antifouling coatings.

Background Yak (Bos grunniens) mainly inhabiting Tibet Plateau, displayed a high incidence of diarrhea due to harsh living environment and nutritional deficit. Gut microbial community has been reported to be closely related to many diseases including diabetes, obesity and inflammatory bowel disease, but information regarding diarrheic influence on gut microbiota in yaks remains scarce. Here, this study was performed to investigate the gut bacterial and fungal alternations of diarrheic yaks. Results Results revealed that the gut bacterial and fungal communities of diarrheic yaks showed a distinct decline in alpha diversity, accompanied by significant shifts in taxonomic compositions. Specifically, diarrhea caused a distinct increase in the relative abundance of 1 phylum and 8 genera as well as a distinct decrease in 3 phyla and 30 genera. Fungal taxonomic analysis indicated that the relative richness of 1 phylum and 2 genera dramatically increased, whereas the relative richness of 2 phylum and 43 genera significantly decreased during diarrhea. Surprisingly, 2 bacterial genera and 5 fungal genera even cannot be detected in the gut microbiota of diarrheic yaks. Conclusions In summary, this study indicated that the gut bacterial and fungal compositions and diversities of yaks altered significantly during diarrhea. Moreover, these findings also contribute to understanding the gut microbial composition and diversity of yaks and developing strategies to alleviate and prevent diarrhea from gut microbial perspective.

Uniform designs have been widely applied in engineering and sciences’ innovation. When a lot of quantitative factors are investigated with as few runs as possible, a supersaturated uniform design with good overall and projection uniformity is needed. By combining combinatorial methods and stochastic algorithms, such uniform designs with flexible numbers of columns are constructed in this article under the wrap-around $$L_2$$ -discrepancy. Compared with the existing designs, the new designs and their two-dimensional projections not only have less aberration, but also have lower discrepancy. Furthermore, some novel theoretical results on the minimum-aberration, uniform and uniform projection designs are obtained.

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34 nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE.

In the present work, approaches of the Computational Fluid Dynamics (CFD) simulation, the Particle Image Velocimetry (PIV) measurement, and the spinning experiment were applied to investigate the phenomenon of air recirculation in blunt-die melt-blown airflow. Firstly, the characteristics of air recirculation were explored by CFD simulation. The simulation results predicted that the air recirculation generated a lateral air velocity along the nose-piece direction. Then, the air circulation was experimental verified by using PIV technique. The PIV results confirmed the predicted conclusions of CFD simulation. Finally, the effect of air recirculation on the microfiber spinning during the melt-blown process was experimentally investigated by a spinning experiment using a blunt die with nose-piece width of 2.56 mm. The spinning results indicated that the air circulation had a tendency of splitting the normal polymeric stream, which played negative effect on the continuity of microfiber spinning. This work is expected to provide some clues to melt-blown die design and the quality control of nonwoven products.

A glucose-mediated drug delivery system would be highly satisfactory for diabetes diagnosis since it can intelligently release drug based on blood glucose levels. Herein, a glucose-responsive drug delivery system by integrating glucose-responsive poly(3-acrylamidophenylboronic acid) (PAPBA) functionalized hollow mesoporous silica nanoparticles (HMSNs) with transcutaneous microneedles (MNs) has been designed. The grafted PAPBA serves as gatekeeper to prevent drug release from HMSNs at normoglycemic levels. In contrast, faster drug release is detected at a typical hyperglycemic level, which is due to the change of hydrophilicity of PAPBA at high glucose concentration. After transdermal administration to diabetic rats, an effective hypoglycemic effect is achieved compared with that of subcutaneous injection. These observations indicate that the designed glucose-responsive drug delivery system has a potential application in diabetes treatment.

A Li1.2Ni0.13Co0.13Mn0.54O2 cathode material is prepared by a kilogram-scale carbonate co-precipitation method assisted with nano-grinding. Uniform hierarchical structure with nano-scale building blocks and low mixing degree of lithium and nickel are achieved. The obtained Li1.2Ni0.13Co0.13Mn0.54O2 cathode material shows high initial Coulombic efficiency and capacity delivery, attractive cycling stability, and high rate performance. At 1 C and 25 °C, it presents a higher discharge capacity of 266.3 mAh g−1, and the capacity retention rates are 97.7% after 300 cycles and 92.8% after 500 cycles, respectively. Excellent high rate discharge capacities of 252.0 and 113.3 mAh g−1 are obtained at 1 and 30 C, respectively. In addition, outstanding temperature dependency discharge capacities are gained. The pouch-type full cell fabricated by this cathode and graphite anode exhibits good cycling performance with 85.5% capacity retention after 350 cycles at 5 mA.

To better understand the historical and projected future climatology and hydrologic impacts of rainfall over the Hawaiian Islands, regional climate simulations over the main Hawaiian Islands were conducted for two 10-year periods using the Weather Research and Forecasting (WRF) model in two nested domains. The first (historical) simulation was driven by the ERA-Interim global reanalysis data and observed sea surface temperature from October 2002 to September 2012. The second simulation used the Pseudo Global Warming (PGW) method to perturb historical conditions with climate change signals taken from global climate model averages. Eighty-one vertical layers were used to better resolve the trade wind inversion (TWI). Results show that the historical simulation reproduces the mean surface temperature, relative humidity, and winds with low biases and high spatial correlations. Additionally, for the historical simulation, the aggregated daily and hourly rainfall probability density functions (PDFs) and rainfall spatial-temporal distributions were well simulated, likely because WRF captured the TWI properties well. For the PGW (future) simulation, the mean rainfall increased by 2.2% in the dry season and 12.5% in the wet season; the average annual increase was 7.8%. The TWI base height decreases in future dry seasons leading to reduced rainfall on the upwind sides of high mountains. Interactions between the complex terrain and the TWI led to heterogeneous changes in patterns of future rainfall across Hawai‘i, including more than a 20% increase in extreme rates in the dry season and a ~ 10% increase during the wet season.

Acute lymphoblastic leukemia (ALL) is the most common malignant hematological diseases in children. An immunosuppressive microenvironment, particularly regulatory T cell (Treg) infiltration, has been documented to be highly associated with childhood ALL. This present study, based on genetic factors, was aimed at investigating the mutations potentially involved in the immunosuppressive microenvironment in childhood ALL. After whole-exome sequencing was used on DNA extracted from the T cells of ALL bone marrow samples, we found the FOXC1 H446HG induced a increased Treg while decreased cytotoxic T lymphocyte (CTL) in bone marrow. The mutation of FOXC1 in T cell promoted the proliferation of leukemia cells in vitro and in vivo. CpG islands formed by insertion mutation led to an abnormal increase in exon methylation and were associated with the suppression of FOXC1. Decreased FOXC1 attenuated the transcription of HDAC1, thus resulting in the activation of KLF10 through increasing H3K27 acetylation in the promoter region. In conclusion, the de novo insertion mutation in FOXC1 induced suppression of FOXC1, thereby promoting a Treg/CTL shift in the ALL immune microenvironment. The FOXC1 H446HG mutation might be a potential therapeutic target for ALL in the future.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.

L-glutamate oxidase (GLOD) and L-amino acid oxidase (AAO) were reported to be capable of convert L-glutamic acid to α-aketoglutaric acid (α-KG). These two enzymes gene have been successfully expressed by using pHBM905BDM in Pichia pastoris to produce α-aketoglutaric acid from L-glutamic acid in our previous studies. Here these two enzymes were displayed on P. pastoris to achieve the conversion. We constructed multi-copy expression plasmids using plasmid pHBM905BDM. By using this plasmid, multi-copy strains were constructed and named as PGLOD(1–3)-AGα1 and PAAO(1–3)-AGα1, respectively. The following results showed that expression of GLOD(1–3)-AGα1 and AAO(1–3)-AGα1 in multi-copy strains increased as designed and strain PGLOD3-AGα1 and PAAO3-AGα1 was chosen for high-density fermentation and enzyme activity experiments. By using a multi-copy expression approach and high-density fermentation, we achieved a GLOD expression yield of 688.5 U/g dry cell weight and AAO expression yield of 626.7 U/g dry cell weight. By using displayed GLOD, the average production rate of L-glutamic acid to α-KG was 6.22 g/L/h and the highest α-KG titer (124.5 g/L) was converted from 135 g/L L-glutamic acid. By using displayed AAO, the average production rate of L-glutamic acid to α-KG was 5.78 g/L/h and the highest α-KG titer (115.6 g/L) was converted from 135 g/L L-glutamic acid. It showed that displaying enzymes on P. pastoris are suitable for use in industrial applications.

A facile method was employed to in situ prepare hierarchical mesoporous Fe3O4@C nanofoams through pyrolysis of a post-treated MIL-53(Fe) precursor. Well-defined carbon network-encapsulated ultrasmall and uniform Fe3O4 octahedrons can be obtained by controlling the pyrolysis temperature. This unique artificial shows the excellent lithium storage performance. A reversible discharge capacity of 861.9 mAh·g−1 is observed at 0.1 A·g−1 after 300 cycles. Even at a high current density of 1 A·g−1, the reversible discharge capacity can still reach 605.2 mAh·g−1 after 500 cycles. Good rate capability is also observed, as the specific discharge capacities are 833.6, 729.9, 666.8, 643.6 and 635.6 mAh·g−1 at current density of 0.2, 0.5, 0.8, 1.0 and 1.2 A·g−1, respectively. The attractive electrochemical performance of Fe3O4@C nanofoams should be attributed to the hierarchical foam-like structure, which can effectively relieve the volume change during the lithiation/delithiation process and facilitate fast lithium-ion and electron transport.

Ecosystems respond to climatic and anthropogenic forcings with regime shifts and reorganizations of their system structures. In river basins, changes in sediment transport can have cascading effects that cause ecosystem regime shifts. The Yellow River, once the world’s most sediment-rich river, has experienced dramatic regime shifts. Although recent intervention has returned sediment discharge in the Yellow River to pristine levels, our understanding of previous regime shifts remains inadequate, particularly for the regime shift to a sediment rich period during early historical time. We reanalyzed previous datasets to clarify the first historical sediment transport regime shift in the Yellow River. Our results show that while historical climatic changes (e.g., the Medieval Warm Period, about 900–1100 AD) caused changes in sediment transport, a regime shift occurred only under increased forcing from anthropogenic stresses (started from about 1350 AD, reached the tipping point after 1900 AD). This unique behavior of the Yellow River under increasing anthropogenic forces may provide perspective for sustainable river basin management.

The gold dissolution in anoxic cyanide solution in the presence of chalcopyrite was studied with a rotating disc electrode. It was found that the presence of chalcopyrite reduced and enhanced the dissolution activity of pure gold in the low and high potential regions, respectively. The dissolution of gold was diffusion-controlled at low potentials (≤177 mV) and low cyanide concentrations (≤980 mg/L); however, above the cyanide concentration of 980 mg/L, the current density of gold decreased and the dissolution of gold changed from diffusion-control to electrochemical reaction-control. At high potentials (>177 mV), gold dissolution was always controlled by diffusion. In cyanide solution containing chalcopyrite, appropriate increase of pH value and temperature could accelerate the dissolution of gold, but high pH value would promote the generation of passivation, which was harmful for the dissolution of gold in cyanide solution.

Toll-like receptor (TLR) signaling pathways need to be tightly controlled to avoid excessive inflammation and unwanted damage to the host. Myeloid differentiation primary response gene 88 (MyD88) is a critical adaptor of TLR signaling. Here, we identified the speckle-type POZ protein (SPOP) as a MyD88-associated protein. SPOP was recruited to MyD88 following TLR4 activation. TLR4 activation also caused the translocation of SPOP from the nucleus to the cytoplasm. SPOP depletion promoted the aggregation of MyD88 and recruitment of the downstream signaling kinases IRAK4, IRAK1 and IRAK2. Consistently, overexpression of SPOP inhibited the TLR4-mediated activation of NF-κB and production of inflammatory cytokines, whereas SPOP depletion had the opposite effects. Furthermore, knockdown of SPOP increased MyD88 aggregation and inflammatory cytokine production upon TLR2, TLR7 and TLR9 activation. Our findings reveal a mechanism by which MyD88 is regulated and highlight a role for SPOP in limiting inflammatory responses.

Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced primary ovarian insufficiency (POI). However, ensuring that stem cells home to the ovary to improve their effects on ovarian injury is challenging. This research aimed to directly inject ovarian tissue with hAD-MSCs and improve the homing of stem cells to the ovary. The animals were divided into POI, hAD-MSC (tail vein) treatment, hAD-MSC (in situ) treatment, and control groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). The hAD-MSCs isolated from the amnion were injected into the tail vein or ovary of POI rats. The estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, and proteome of the ovaries were evaluated. hAD-MSCs were successfully isolated and cultured from the amnion. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantation increased body weight, improved the AMH levels and follicle numbers, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs (in situ) upregulated 24 proteins and downregulated 4 proteins. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantations can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. The paracrine proteome of hAD-MSCs in the ovarian microenvironment can protect against chemotherapy-induced damage by reducing apoptosis and promoting angiogenesis, cell proliferation, and gene expression.

Brain injury has been proposed as the major cause of the poor outcomes associated with intracerebral hemorrhage (ICH). Emerging evidence indicates that the nuclear receptor, peroxisome proliferator-activated receptor β/δ (PPAR-β/δ), plays a crucial role in the pathological process of central nervous impairment. The present study was undertaken to evaluate the protective effects of PPAR-β/δ activation using a selective PPAR-β/δ agonist, GW0742, against brain injury after ICH in a mouse model. ICH was induced by intravenous injection of collagenase into the right caudate putamen. To examine the protective effect of PPAR-β/δ activation against ICH-induced brain injury, mice were either intraperitoneally injected with GW0742 (3 mg/kg, body weight) or saline (control group) 30 min before inducing ICH. Behavioral dysfunction was evaluated 24 and 72 h after injury. Then, all mice were killed to assess hematoma volume, brain water content, and blood–brain barrier (BBB) permeability. TUNEL and Nissl staining were performed to quantify the brain injury. The expression of PPAR-β/δ, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, Bcl-2-related X-protein (Bax), and B-cell lymphoma 2 (Bcl-2) in the perihematomal area was examined by immunohistochemistry and western blotting analysis. Mice treated with GW0742 showed significantly less severe behavioral deficits compared to the control group, accompanied by increased expression of PPAR-β/δ and Bcl-2, and increased expression of IL-1β, TNF-α, and Bax decreased simultaneously in the GW0742-treated group. Furthermore, the GW0742-pretreated group showed significantly less brain edema and BBB leakage. Neuronal loss was attenuated, and the number of apoptotic neuronal cells in perihematomal tissues reduced, in the GW0742-pretreated group compared to the control group. However, the hematoma volume did not decrease significantly on day 3 after ICH. These results suggest that the activation of PPAR-β/δ exerts a neuroprotective effect on ICH-induced brain injury, possibly through anti-inflammatory and anti-apoptotic pathways.

Thiram is a widely known tibial dyschondroplasia (TD) inducer. TD, a common metabolic cartilage disease, presents in rapidly growing poultry birds. There are evidences that miRNAs are involved in diverse aspects of normal skeletal development, but very less is known about the role of miRNAs in TD. Therefore, this study aimed to determine which genes and pathways show differential expression between TD suffered chickens and normal chickens. We collected growth plates from ten-days-old TD chickens and control chickens and performed high-throughput RNA sequencing (RNA-Seq). Afterwards, target prediction, GO annotation and KEGG pathway analysis were carried out to understand the role of DEMs (differentially expressed microRNAs). We obtained 96,884,760 and 94,574,290 clean reads and identified 17 significant DEMs between the TD and control groups. Functional enrichment analysis of DEMs indicated that the putative targets of miRNAs were remarkably enriched in bone-related pathways, such as Notch, MAPK and Autophagy. Overall, this study provides detailed understanding about the pathogenesis of thiram induced TD and new insights towards the molecular mechanism of miRNAs.

Ti3C2 MQDs were synthesized using an effective fluorine-free method with excitation/emission maxima at 390/490 nm and a fluorescence quantum yield of 11.78%. In contrast to the traditional, hazardous, and time-consuming process of HF pretreatment, our fluorine-free method is safe and simple. Acetylcholinesterase (AChE) could catalyze the hydrolysis of acetylthiocholine (ATCh) to produce thiocholine which was further reacted with Ehrman's reagent and decomposed to form a yellow product 2-nitro-5-thiobenate anion (TNB). Due to the obvious overlap between the excitation spectrum of Ti3C2 MQDs and the absorption spectrum of TNB, AChE catalyzed the hydrolysis of substrate DTNB/ATCh to form TNB, which can effectively quench the fluorescence of Ti3C2 MQDs through the inner filter effect (IFE). However, the presence of organophosphorus (OPs) inhibited the activity of AChE, leading to a less expressed IFE and increasing recovery of fluorescence. This was used for the quantification of OPs with a detection limit of 0.20 μg·L-1. Moreover, with the constant increase of AChE activity, the color of the reaction system changed visibly from colorless to yellow, and then from yellow to colorless with further continuous addition of OPs. A colorimetric detection with a paper-based sensor of AChE activity and OP concentration was also fabricated by analyzing changes in RGB value using a smartphone APP. In this work, we proposed an effective fluorescence/colorimetric two-mode detection method, which opened a new horizon to detect other targets.

The Ti3C2 MXene quantum dots (Ti3C2 MQDs) derived from Ti3C2 MXene have received much attention because of their remarkable advantages in biosensing. Nevertheless, the functionalization of Ti3C2 MQDs to improve their properties is just in its infant stage. Herein, we firstly synthesized nitrogen and boron co-doped Ti3C2 MQDs (N, B-Ti3C2 MQDs) with good water solubility, strong stability, and high optical characteristics. The N, B-Ti3C2 MQDs exhibit excitation wavelength-dependent blue photoluminescence with optimal excitation/emission peaks at 335/439 nm. Nowadays, the development of fast and real-time detection of tetracycline (TC) in animal derived food is very essential. In this work, a novel point-of-care testing (POCT) platform was established based on ratiometric fluorescence method using N, B-Ti3C2 MQDs coupled with Eu3+. Upon addition of TC in the Eu3+/N, B-MQDs system, blue fluorescence emission of N, B-Ti3C2 MQDs was quenched and red fluorescence emission of Eu3+ was enhanced gradually, which was ascribed to the synergistic inner filter effect and antenna effect. Moreover, we prepared test papers with N, B-Ti3C2 MQDs and Eu3+ for TC detection based on the change of fluorescence color, which could be recognized by color recognizer app installed in the smartphone. Therefore, great promise for POCT of TC is given with the merits of simplicity and visible detection possibility. The proposed method demonstrated a low detection limit of 20 nM. Application of the platform for TC quantification in milk samples opened a novel means for the potential use of N, B-Ti3C2 MQDs in food safety.

In both physical and computer experiments, U-type designs, including Latin hypercube designs, are commonly used. Two major approaches for evaluating U-type designs are orthogonality and space-filling criteria. Level permutations and level expansions are powerful tools for generating good U-type designs under the above criteria in the literature. In this paper, we systematically study the theoretical properties of U-type designs before and after level permutations and expansions. We establish the relationships between the initial designs’ generalized word-length patterns (GWLP) and the generated designs’ orthogonal and space-filling properties. Our findings generalize the existing results and provide theoretical justifications for the current level permutation and expansion algorithms.

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year., The quality of immune response to SARS-CoV-2 is thought to wane over time, but it is unclear how long it can persist. Here the authors show persistent immune responses in a large number of patients over the course of a 1-year follow-up from the time of recovery from COVID-19.

Background Diarrhea is an important ailment limiting the production of the Tibetan pig industry. Dynamic balance of the intestinal microbiota is important for the physiology of the animal. The objective of this work was to study fungal diversity in the feces of early weaning Tibetan piglets in different health conditions. Results In the present study, we performed high-throughput sequencing to characterize the fungal microbial diversity in healthy, diarrheal and treated Tibetan piglets at the Tibet Autonomous Region of the People’s Republic of China. The four alpha diversity indices (Chao1, ACE, Shannon and Simpson) revealed no significant differences in the richness across the different groups (P > 0.05). In all samples, the predominant fungal phyla were Ascomycota, Basidiomycota and Rozellomycota. Moreover, the healthy piglets showed a higher abundance of Ascomycota than the treated ones with a decreased level of Basidiomycota. One phylum (Rozellomycota) showed higher abundance in the diarrheal piglets than in the treated. At genus level, compared with that to the healthy group, the proportion of Derxomyces and Lecanicillium decreased, whereas that of Cortinarius and Kazachstania increased in the diarrheal group. The relative abundances of Derxomyces, Phyllozyma and Hydnum were higher in treated piglets than in the diarrheal ones. Conclusions A decreased relative abundance of beneficial fungi (e.g. Derxomyces and Lecanicillium) may cause diarrhea in the early-weaned Tibetan piglets. Addition of probiotics into the feed may prevent diarrhea at this stage. This study presented the fungal diversity in healthy, diarrheal and treated early-weaned Tibetan piglets.