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To determine whether ambient air pollutants and meteorological variables are associated with daily COVID-19 incidence. A retrospective cohort from January 25 to February 29, 2020. Cities of Wuhan, Xiaogan, and Huanggang, China. The COVID-19 cases detected each day. We collected daily data of COVID-19 incidence, 8 ambient air pollutants (particulate matter of ≤2.5 µm [PM2.5], particulate matter ≤10 µm [PM10], sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and maximum 8-h moving average concentrations for ozone [O3-8h]) and 3 meteorological variables (temperature, relative humidity, and wind) in China's 3 worst COVID-19-stricken cities during the study period. The multivariate Poisson regression was performed to understand their correlation. Daily COVID-19 incidence was positively associated with PM2.5 and humidity in all cities. Specifically, the relative risk (RR) of PM2.5 for daily COVID-19 incidences were 1.036 (95% confidence interval [CI], 1.032-1.039) in Wuhan, 1.059 (95% CI, 1.046-1.072) in Xiaogan, and 1.144 (95% CI, 1.12-1.169) in Huanggang. The RR of humidity for daily COVID-19 incidence was consistently lower than that of PM2.5, and this difference ranged from 0.027 to 0.111. Moreover, PM10 and temperature also exhibited a notable correlation with daily COVID-19 incidence, but in a negative pattern The RR of PM10 for daily COVID-19 incidence ranged from 0.915 (95% CI, 0.896-0.934) to 0.961 (95% CI, 0.95-0.972, while that of temperature ranged from 0.738 (95% CI, 0.717-0.759) to 0.969 (95% CI, 0.966-0.973). Our data show that PM2.5 and humidity are substantially associated with an increased risk of COVID-19 and that PM10 and temperature are substantially associated with a decreased risk of COVID-19.

Supported metal nanoclusters consisting of several dozen atoms are highly attractive for heterogeneous catalysis with unique catalytic properties. However, the metal nanocluster catalysts face the challenges of thermal sintering and consequent deactivation owing to the loss of metal surface areas particularly in the applications of high-temperature reactions. Here, we report that sulfur—a documented poison reagent for metal catalysts—when doped in a carbon matrix can stabilize ~1 nanometer metal nanoclusters (Pt, Ru, Rh, Os, and Ir) at high temperatures up to 700 °C. We find that the enhanced adhesion strength between metal nanoclusters and the sulfur-doped carbon support, which arises from the interfacial metal-sulfur bonding, greatly retards both metal atom diffusion and nanocluster migration. In catalyzing propane dehydrogenation at 550 °C, the sulfur-doped carbon supported Pt nanocluster catalyst with interfacial electronic effects exhibits higher selectivity to propene as well as more stable durability than sulfur-free carbon supported catalysts. The sulfur is a documented poison reagent for metal catalysts. Here the authors show when doped in a carbon matrix, sulfur can enhance the adhesion strength and eventually suppress the metal sintering, which improve the performance of propane dehydrogenation by strong chemical/electronic interactions.

Metal–support interaction is of great significance for catalysis as it can induce charge transfer between metal and support, tame electronic structure of supported metals, impact adsorption energy of reaction intermediates, and eventually change the catalytic performance. Here, we report the metal size-dependent charge transfer reversal, that is, electrons transfer from platinum single atoms to sulfur-doped carbons and the carbon supports conversely donate electrons to Pt when their size is expanded to ~1.5 nm cluster. The electron-enriched Pt nanoclusters are far more active than electron-deficient Pt single atoms for catalyzing hydrogen evolution reaction, exhibiting only 11 mV overpotential at 10 mA cm −2 and a high mass activity of 26.1 A mg −1 at 20 mV, which is 38 times greater than that of commercial Pt/C. Our work manifests that the manipulation of metal size-dependent charge transfer between metal and support opens new avenues for developing high-active catalysts. The charge transfer between metal and support is significant for catalysis, but little attention has been focused on charge transfer tuned by metal size. Here, authors report a metal size-dependent reversal of charge transfer between metal and carbon support in hydrogen evolution electrocatalysts.

Discriminative Correlation Filters (DCF) have been shown to achieve impressive performance in visual object tracking. However, existing DCF-based trackers rely heavily on learning regularised appearance models from invariant image feature representations. To further improve the performance of DCF in accuracy and provide a parsimonious model from the attribute perspective, we propose to gauge the relevance of multi-channel features for the purpose of channel selection. This is achieved by assessing the information conveyed by the features of each channel as a group, using an adaptive group elastic net inducing independent sparsity and temporal smoothness on the DCF solution. The robustness and stability of the learned appearance model are significantly enhanced by the proposed method as the process of channel selection performs implicit spatial regularisation. We use the augmented Lagrangian method to optimise the discriminative filters efficiently. The experimental results obtained on a number of well-known benchmarking datasets demonstrate the effectiveness and stability of the proposed method. A superior performance over the state-of-the-art trackers is achieved using less than 10% deep feature channels.

PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18–75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0–1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1–14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5–23·5) months. 28 (54%; 95% CI 35–68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39–80) had a pathological complete response. 38 (73%; 95% CI 59–84) of 52 patients had a complete response. Grade 3–5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section.

Efficient and robust facial landmark localisation is crucial for the deployment of real-time face analysis systems. This paper presents a new loss function, namely Rectified Wing (RWing) loss, for regression-based facial landmark localisation with Convolutional Neural Networks (CNNs). We first systemically analyse different loss functions, including L2, L1 and smooth L1. The analysis suggests that the training of a network should pay more attention to small-medium errors. Motivated by this finding, we design a piece-wise loss that amplifies the impact of the samples with small-medium errors. Besides, we rectify the loss function for very small errors to mitigate the impact of inaccuracy of manual annotation. The use of our RWing loss boosts the performance significantly for regression-based CNNs in facial landmarking, especially for lightweight network architectures. To address the problem of under-representation of samples with large pose variations, we propose a simple but effective boosting strategy, referred to as pose-based data balancing. In particular, we deal with the data imbalance problem by duplicating the minority training samples and perturbing them by injecting random image rotation, bounding box translation and other data augmentation strategies. Last, the proposed approach is extended to create a coarse-to-fine framework for robust and efficient landmark localisation. Moreover, the proposed coarse-to-fine framework is able to deal with the small sample size problem effectively. The experimental results obtained on several well-known benchmarking datasets demonstrate the merits of our RWing loss and prove the superiority of the proposed method over the state-of-the-art approaches.

Interactions between early developing Schistosoma mansoni larval stages and the hemolymph of its snail intermediate host represent the first molecular encounter with the snail's immune system. To gain a more comprehensive understanding of this early parasite-host interaction, biotinylated sporocyst tegumental membrane (Mem) proteins and larval transformation proteins (LTP) were affixed to streptavidin-agarose beads and used as affinity matrices to enrich for larval-reactive plasma proteins from susceptible (NMRI) and resistant (BS-90) strains of the snail Biomphalaria glabrata. Nano-LC/MS-MS proteomic analyses of isolated plasma proteins revealed a diverse array of 94 immune-and nonimmune-related plasma proteins. Included among the immune-related subset were pattern recognition receptors (lectins, LPS-binding protein, thioester-containing proteins-TEPs), stress proteins (HSP60 and 70), adhesion proteins (dermatopontins), metalloproteases (A Disintegrin And Metalloproteinase (ADAM), ADAM-related Zn proteinases), cytotoxins (biomphalysin) and a Ca2+-binding protein (neo-calmodulin). Variable immunoglobulin and lectin domain (VIgL) gene family members, including fibrinogen-related proteins (FREPs), galectin-related proteins (GREPs) and C-type lectin-related proteins (CREPs), were the most prevalent of larval-reactive immune lectins present in plasma. FREPs were highly represented, although only a subset of FREP subfamilies (FREP 2, 3 and 12) were identified, suggesting potential selectivity in the repertoire of plasma lectins recognizing larval glycoconjugates. Other larval-binding FREP-like and CREP-like proteins possessing a C-terminal fibrinogen-related domain (FReD) or C-type lectin binding domain, respectively, and an Ig-fold domain also were identified as predicted proteins from the B. glabrata genome, although incomplete sequence data precluded their placement into specific FREP/CREP subfamilies. Similarly, a group of FReD-containing proteins (angiopoeitin-4, ficolin-2) that lacked N-terminal Ig-fold(s) were identified as a distinct group of FREP-like proteins, separate from the VIgL lectin family. Finally, differential appearance of GREPs in BS-90 plasma eluates, and others proteins exclusively found in eluates of the NMRI strain, suggested snail strain differences in the expression of select larval-reactive immune proteins. This hypothesis was supported by the finding that differential gene expression of the GREP in BS-90 and ADAM in NMRI snail strains generally correlated with their patterns of protein expression. In summary, this study is the first to provide a global comparative proteomic analysis of constitutively expressed plasma proteins from susceptible and resistant B. glabrata strains capable of binding early-expressed larval S. mansoni proteins. Identified proteins, especially those exhibiting differential expression, may play a role in determining immune compatibility in this snail host-parasite system. A complete listing of raw peptide data are available via ProteomeXchange using identifier PXD004942.

Background The number of coronavirus disease 2019 (COVID-19) cases has rapidly increased all over the world. Specific information about immunity in non-survivors with COVID-19 is scarce. This study aimed to analyse the clinical characteristics and abnormal immunity of the confirmed COVID-19 non-survivors. Methods In this single-centered, retrospective, observational study, we enrolled 125 patients with COVID-19 who were died between January 13 and March 4, 2020 in Renmin Hospital of Wuhan University. A total of 414 randomly recruited patients with confirmed COVID-19 who were discharged from the same hospital during the same period served as control. The demographic, clinical characteristics and laboratory findings at admission, and treatment used in these patients were collected. The immunity-related risk factors associated with in-hospital death were tested by logistic regression models and Receiver Operating Characteristic (ROC) curve. Results Non-survivors (70 years, IQR: 61.5–80) were significantly older than survivors (54 years, IQR: 37–65) ( P  <  0.001). 56.8% of non-survivors was male. Nearly half of the patients (44.9%) had chronic medical illness. In non-survivors, hypertension (49.6%) was the most common comorbidity, followed by diabetes (20.0%) and coronary heart disease (16.0%). The common signs and symptoms at admission of non-survivors were fever (88%), followed by cough (64.8%), dyspnea (62.4%), fatigue (62.4%) and chest tightness (58.4%). Compared with survivors, non-survivors had higher white blood cell (WBC) count (7.85 vs 5.07 × 10 9 /L), more elevated neutrophil count (6.41 vs 3.08 × 10 9 /L), smaller lymphocyte count (0.69 vs 1.20 × 10 9 /L) and lower platelet count (172 vs 211 × 10 9 /L), raised concentrations of procalcitonin (0.21 vs 0.06 ng/mL) and CRP (70.5 vs 7.2 mg/L) ( P  < 0.001). This was accompanied with significantly decreased levels of CD3 + T cells (277 vs 814 cells/μl), CD4 + T cells (172 vs 473 cells/μl), CD8 + T cells (84 vs 262.5 cells/μl, P  < 0.001), CD19 + T cells (88 vs 141 cells/μl) and CD16 +  56 + T cells (79 vs 128.5 cells/μl) ( P  < 0.001). The concentrations of immunoglobulins (Ig) G (13.30 vs 11.95 g/L), IgA (2.54 vs 2.21 g/L), and IgE (71.30 vs 42.25 IU/ml) were increased, whereas the levels of complement proteins (C)3 (0.89 vs 0.99 g/L) and C4 (0.22 vs 0.24 g/L) were decreased in non-survivors when compared with survivors (all P  < 0.05). The non-survivors presented lower levels of oximetry saturation (90 vs 97%) at rest and lactate (2.40 vs 1.90 mmol/L) ( P  < 0.001). Old age, comorbidity of malignant tumor, neutrophilia, lymphocytopenia, low CD4 + T cells, decreased C3, and low oximetry saturation were the risk factors of death in patients with confirmed COVID-19. The frequency of CD4 + T cells positively correlated with the numbers of lymphocytes ( r  = 0.787) and the level of oximetry saturation ( r  = 0.295), Whereas CD4 + T cells were negatively correlated with age ( r  =-0.323) and the numbers of neutrophils ( r  = − 0.244) (all P  < 0.001). Conclusions Abnormal cellular immunity and humoral immunity were key features of non-survivors with COVID-19. Neutrophilia, lymphocytopenia, low CD4 + T cells, and decreased C3 were immunity-related risk factors predicting mortality of patients with COVID-19.

Impaired spiral artery remodeling (IRSA) underpins the great obstetrical syndromes. We previously demonstrated that intrauterine infection with the periodontal pathogen, Porphyromonas gingivalis, induces IRSA in rats. Since our previous studies only examined the end stage of arterial remodeling, the aim of this study was to identify the impact of P. gingivalis infection on the earlier stages of remodeling. Gestation day (GD) 11 specimens, a transition point between trophoblast-independent remodeling and the start of extravillous trophoblast invasion, were compared to late stage GD18 tissues. P. gingivalis was found in decidual stroma of GD11 specimens that already had reduced spiral artery remodeling defined as smaller arterial lumen size, increased retention of vascular smooth muscle, and decreased invasion by extravillous trophoblasts. At GD11, P. gingivalis -induced IRSA coincided with altered uterine natural killer (uNK) cell populations, decreased placental bed expression of interleukin-18 (IL-18) with increased production of temperature requirement A1 (Htra1), a marker of oxidative stress. By GD18, placental bed IL-18 and Htra1 levels, and uNK cell numbers were equivalent in control and infected groups. However, infected GD18 placental bed specimens had decreased TNF + T cells. These results suggest disturbances in placental bed decidual stroma and uNK cells are involved in P. gingivalis -mediated IRSA.

Disturbed homeostasis of gut microbiota has been suggested to be closely associated with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by weight loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body weight loss and colon shortening of 5-Fu treated mice. In addition, the fecal transplant from 5-Fu treated mice reduced body weight and colon length of vancomycin-pretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathological process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.