An Inherited Allele Confers Prostate Cancer Progression and Drug Resistance via RFX6/HOXA10-Orchestrated TGFß Signaling.

Genetic and epigenetic alterations are cancer hallmark characteristics. However, the role of inherited cancer predisposition alleles in co-opting lineage factor epigenetic reprogramming and tumor progression remains elusive. Here the FinnGen cohort phenome-wide analysis, along with multiple genome-wide association studies, has consistently identified the rs339331-RFX6/6q22 locus associated with prostate cancer (PCa) risk across diverse populations. It is uncovered that rs339331 resides in a reprogrammed androgen receptor (AR) binding site in PCa tumors, with the T risk allele enhancing AR chromatin occupancy. RFX6, an AR-regulated gene linked to rs339331, exhibits synergistic prognostic value for PCa recurrence and metastasis. This comprehensive in vitro and in vivo studies demonstrate the oncogenic functions of RFX6 in promoting PCa cell proliferation and metastasis. Mechanistically, RFX6 upregulates HOXA10 that profoundly correlates with adverse PCa outcomes and is pivotal in RFX6-mediated PCa progression, facilitating the epithelial-mesenchymal transition (EMT) and modulating the TGFß/SMAD signaling axis. Clinically, HOXA10 elevation is associated with increased EMT scores, tumor advancement and PCa recurrence. Remarkably, reducing RFX6 expression restores enzalutamide sensitivity in resistant PCa cells and tumors. This findings reveal a complex interplay of genetic and epigenetic mechanisms in PCa pathogenesis and drug resistance, centered around disrupted prostate lineage AR signaling and abnormal RFX6 expression.

Construction of Marigold-like Poly(vinyl alcohol) Microspheres for Catalytic Microreactors.

It has long been pursued to develop polymer microspheres with various special morphologies and structures for better results in applications such as catalysis, drug delivery, and bioscaffolds. However, it remains a challenge to develop a facile method to produce poly(vinyl alcohol) (PVA) microspheres with special morphologies. Herein, a micron-sized marigold-like poly(vinyl alcohol) (CE-PVATPA) microsphere was engineered and fabricated by a feasible strategy, that is, emulsification-cross-linking, freeze-drying, and secondary acetal reaction steps. The morphological evolution of microspheres was systematically investigated under different conditions, and the procedure of constructing PVA microspheres with stabilizing marigold-like structures was proposed. More importantly, a specially structured PVA microsphere microreactor synergistically loading palladium metal nanoparticles (CE-PVATPA@Pd) for the heterogeneous catalyst 4-nitrophenol (4-NP) could be further demonstrated, which indicated high catalytic activity and excellent recyclability. The resultant stabilized fabricating method is promising to provide valuable guidance for the design and fabrication of a high-performance PVA microsphere microreactor.

Arsenophonus Interacts with Buchnera to Improve Growth Performance of Aphids under Amino Acid Stress.

Amino acids play a crucial role in the growth and development of insects. Aphids cannot ingest enough amino acids in plant phloem to meet their requirements, and therefore, they are mainly dependent on the obligate symbiont Buchnera aphidicola to synthesize essential amino acids. Besides Buchnera, aphids may harbor another facultative symbiont, Arsenophonus, which alters the requirement of the cotton-melon aphid Aphis gossypii for amino acid. However, it is unclear how Arsenophonus regulates the requirement. Here, we found that Arsenophonus ameliorated growth performance of A. gossypii on an amino acid-deficient diet. A deficiency in lysine (Lys) or methionine (Met) led to changes in the abundance of Arsenophonus. Arsenophonus suppressed the abundance of Buchnera when aphids were fed a normal amino acid diet, but this suppression was eliminated or reversed when aphids were on a Lys- or Met-deficient diet. The relative abundance of Arsenophonus was positively correlated with that of Buchnera, but neither of them was correlated with the body weight of aphids. The relative expression levels of Lys and Met synthase genes of Buchnera were affected by the interaction between Arsenophonus infections and Buchnera abundance, especially in aphids reared on a Lys- or Met-deficient diet. Arsenophonus coexisted with Buchnera in bacteriocytes, which strengthens the interaction. IMPORTANCE The obligate symbiont Buchnera can synthesize amino acids for aphids. In this study, we found that a facultative symbiont, Arsenophonus, can help improve aphids' growth performance under amino acid deficiency stress by changing the relative abundance of Buchnera and the expression levels of amino acid synthase genes. This study highlights the interaction between Arsenophonus and Buchnera to ameliorate aphid growth under amino acid stress.

Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library.

Objective: The objective of this study was to screen lymphoma radiotherapy-resistant genes using CRISPR activation (CRISPRa). Methods: The Human CRISPRa library virus was packaged and then transfected into lymphoma cells to construct an activation library cell line, which was irradiated at the minimum lethal radiation dose to screen radiotherapy-resistant cells. Radiotherapy-resistant cell single-guide RNA (sgRNA) was first amplified by quantitative polymerase chain reaction (qPCR) in the coding region and then subject to next-generation sequencing (NGS) and bioinformatics analysis to screen radiotherapy-resistant genes. Certain radiotherapy-resistant genes were then selected to construct activated cell lines transfected with a single gene so as to further verify the relationship between gene expression and radiotherapy resistance. Results: A total of 16 radiotherapy-resistant genes, namely, C20orf203, MTFR1, TAF1L, MYADM, NIPSNAP1, ZUP1, RASL11A, PSMB2, PSMA6, OR8H3, TMSB4Y, CD300LF, EEF1A1, ATP6AP1L, TRAF3IP2, and SNRNP35, were screened based on the NGS results and bioinformatics analysis of the radiotherapy-resistant cells. Activated cell lines transfected with a single gene were constructed using 10 radiotherapy-resistant genes. The qPCR findings showed that, when compared with the control group, the experimental group had significantly up-regulated mRNA expression of MTFR1, NIPSNAP1, ZUP1, PSMB2, PSMA6, EEF1A1, TMSB4Y and TAF1L (p < 0.05). No significant difference in the mRNA expression of AKT3 or TRAF3IP2 (p > 0.05) was found between the two groups (p > 0.05). Conclusion: The 16 genes screened are potential lymphoma radiotherapy-resistant genes. It was initially determined that the high expression of 8 genes was associated with lymphoma radiotherapy resistance, and these genes could serve as the potential biomarkers for predicting lymphoma radiotherapy resistance or as new targets for therapy.

A Hydrolyzable Supra-amphiphile as a Marangoni Self-Propulsion Fuel for Efficient Macroscopic Supramolecular Self-Assembly.

Self-assembly of µm-to-mm components is important for achieving all-scale ordering with requirements of extra energy for motion and interaction of components. Marangoni flows caused by surfactants on water provide appropriate energy but have limited lifetimes because of the inevitable interfacial aggregation and difficult decomposition of aggregated covalent surfactants that inactivate Marangoni effects. Here we have synthesized a supra-amphiphile Marangoni "fuel"-sodium-4-(benzylideneamino) benzenesulfonate (SBBS)-that can be hydrolyzed in a timely manner to a species without surface activity to extend the motion time by 10-fold. The motion was optimized at pH=2 by a fine equilibrium between the releasing and removal of interfacial SBBS, leading to the self-assembly of millimeter-scaled ordered dimers. The underlying mechanism was interpreted by motion analyses and simulation. This strategy provides an active solution to self-assembly at the µm-to-mm scale, as well as interactive ideas between miniaturized chemical robots.

Wound healing mechanism of antimicrobial peptide cathelicidin-DM.

Background and Purpose: Chronic wound infections and the development of antibiotic resistance are serious clinical problems that affect millions of people worldwide. Cathelicidin-DM, an antimicrobial peptide from Duttaphrynus melanostictus, has powerful antimicrobial activity and wound healing efficacy. So, it could be a potential candidate to address this problem. In this paper, we investigate the wound healing mechanism of cathelicidin-DM to establish a basis for preclinical studies of the drug. Experimental Approach: The effects of cathelicidin-DM on cell proliferation and migration, cytokines, and mitogen-activated protein kinase (MAPK) signaling pathways were examined. Then mice whole skin wound model was constructed to evaluate the wound healing activity of cathelicidin-DM, and further histological changes in the wounds were assessed by hematoxylin-eosin staining (H&E) and immunohistochemical assays. Key Results: Cathelicidin-DM promotes the proliferation of HaCaT, HSF, and HUVEC cells in a concentration-dependent manner and the migration of HSF, HUVEC, and RAW.264.7 cells. Moreover,cathelicidin-DM can involve in wound healing through activation of the MAPK signaling pathway by upregulating phosphorylation of ERK, JNK, and P38. However, cathelicidin-DM didn't affect the secretion of IL-6 and TNF-α. At the animal level, cathelicidin-DM accelerated skin wound healing and early debridement in mice as well as promoted re-epithelialization and granulation tissue formation, α-SMA expression, and collagen I deposition in mice. Conclusion and Implications: Our data suggest that cathelicidin-DM can be engaged in the healing of infected and non-infected wounds through multiple pathways, providing a new strategy for the treatment of infected chronic wounds.

Self-sorting in macroscopic supramolecular self-assembly via additive effects of capillary and magnetic forces.

Supramolecular self-assembly of µm-to-mm sized components is essential to construct complex supramolecular systems. However, the selective assembly to form designated structures at this length scale is challenging because the short-ranged molecular recognition could hardly direct the assembly of macroscopic components. Here we demonstrate a self-sorting mechanism to automatically identify the surface chemistry of µm-to-mm components (A: polycations; B: polyanions) based on the A-B attraction and the A-A repulsion, which is realized by the additivity and the competence between long-ranged magnetic/capillary forces, respectively. Mechanistic studies of the correlation between the magnetic/capillary forces and the interactive distance have revealed the energy landscape of each assembly pattern to support the self-sorting results. By applying this mechanism, the assembly yield of ABA trimers has been increased from 30%~40% under conventional conditions to 100% with self-sorting. Moreover, we have demonstrated rapid and spontaneous self-assembly of advanced chain-like structures with alternate surface chemistry.

A Light-Powered Triboelectric Nanogenerator Based on the Photothermal Marangoni Effect.

The photothermal Marangoni effect enables direct light-to-work conversion, which is significant for realizing the self-propulsion of objects in a noncontact, controllable, and continuous manner. Many promising applications have been demonstrated in micro- and nanomachines, light-driven actuators, cargo transport, and gear transmission. Currently, the related studies about photothermal Marangoni effect-induced self-propulsion, especially rotational motions, remain focused on developing the novel photothermal materials, the structural designs, and the controllable self-propulsion modes. However, extending the related research from the laboratory practice to practical application remains a challenge. Herein, we combined the photothermal Marangoni effect-induced self-propulsion with the triboelectric nanogenerator technology for sunlight intensity determination. Photothermal black silicon, superhydrophobic copper foam with drag-reducing property, and triboelectric polytetrafluoroethylene film were integrated to fabricate a triboelectric nanogenerator. The photothermal-Marangoni-driven triboelectric nanogenerator (PMD-TENG) utilizes the photothermal Marangoni effect-induced self-propulsion to realize the relative motion between the triboelectric layer and the electrode, converting light into electrical signals, with a peak value of 2.35 V. The period of the output electrical signal has an excellent linear relationship with the light intensity. The accessible electrical signal generation strategy proposed here provides a new application for the photothermal Marangoni effect, which could further inspire the practical applications of the self-powered system based on the photothermal Marangoni effect, such as intelligent farming.

Plant secondary metabolite and temperature determine the prevalence of Arsenophonus endosymbionts in aphid populations.

Transmission rate and role in hosts contribute to the prevalence of an endosymbiont. However, factors affecting transmission and role of facultative endosymbionts are still not well understood. Here, we illustrated that host plants and environmental temperatures affected the transmission, relative abundance and role of Arsenophonus in the cotton aphid Aphis gossypii. The transmission rate of this endosymbiont from mother aphids to offspring was relatively lower. High temperatures impeded the transmission, and infection rates declined as aphids were exposed to 30°C. Contents of amino acids and secondary metabolites were remarkably different among host plants. Aphids feeding on zucchini leaves containing a higher titre of amino acids and lower secondary metabolites harboured a relatively lower abundance of Arsenophonus. Concentrations of an amino acid and a plant secondary metabolite, cucurbitacin B, in aphid diet were not associated with Arsenophonus abundance. However, gossypol, another plant secondary metabolite, was strongly related with the abundance. Arsenophonus imparted a fitness benefit to aphids, and the benefit was dependent on host plants and gossypol concentration. In sum, plant secondary metabolite and environmental temperature affect transmission, relative abundance and role of Arsenophonus, which determine the endosymbiont prevalence in aphid populations.

[Effects of the Three Gorges Reservoir Operation on Vertical Distribution of Chlorophyll a and Environmental Factors in Tributaries].

The hydrodynamics and environmental factors in the Xiangxi River (XXR) and Shennong River (SNR), which are tributaries of the Three Gorges Reservoir (TGR), were monitored from July to August (the low water level period) and in October (the impoundment period) in 2018. The vertical distribution characteristics of chlorophyll a and other indicators of the two tributaries were analyzed during the different operation periods, and the factors that affected the vertical distribution in each period were discussed. The results showed that the vertical distribution of dissolved oxygen, water temperature, pH value, and chlorophyll a of the XXR and SNR during the low water level period was relatively consistent. The indexes 0-10 m (0-5 m for chlorophyll a) from the surface of the XXR and SNR, respectively, showed significant stratification and decreased with increasing water depth; the stability index of thermal stratification (RWCS/H) was 13.71-29.07 m-1, which was stable. After the water depth reached 10 m (5 m for chlorophyll a), the indexes tended to be stable along the water depth. During the impoundment period, there was no obvious stratification for each index; the stability index of thermal stratification was 0-0.5 m-1, the stability of the water body was weak, and the vertical variation of each index was relatively stable. The comprehensive trophic state index (TLI) of the XXR and SNR were 55 and 53 during the low water level period, respectively, indicating that they were in a slightly eutrophic state, and 39 and 46 during the impoundment period, respectively, indicating a mesotrophic state. Linear regression analysis showed that chlorophyll a, dissolved oxygen, water temperature, and pH in the two tributaries were significantly correlated in the vertical direction in the low water level period, indicating that dissolved oxygen, water temperature stratification, and pH were important factors affecting the vertical distribution of chlorophyll a. During the impoundment period, a large amount of backflow from the Yangtze River, a large fluctuation in tributary water level, and the decrease in RWCS/H were the important factors that affected the small vertical change in the water body. The enhancement of vertical mixing and the decrease in Zeu/Zmix were the key factors affecting the nutritional status of the water.

Treatment of vitiligo with 308-nm light emitting diode: Our experience from a two-year follow-up of Chinese patients.

BACKGROUND: A light emitting diode (LED), with a wavelength of 308 nm, has been utilized in the dermatologic treatment of vitiligo. OBJECTIVES: We investigated the efficacy and safety of 308-nm LED for use in the treatment of vitiligo. METHODS: We conducted a retrospective study of 70 stable-stage vitiligo patients (with a total of 99 lesions) who received 308-nm LED treatment at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to June 2020. Treatment efficacy was evaluated after 8 treatment sessions, 16 treatment sessions, and the final treatment session, to estimate the percentage of re-pigmentation in the treated area. The Kruskal-Wallis test was used for data analysis. RESULTS: Based on the final treatment session analysis of all 99 lesions, 0 lesions showed no response, 21 lesions showed poor response, 29 lesions showed moderate response, 23 lesions showed good response, and 26 lesions showed excellent response. The efficacy rate was 49.49%, and there was a significant correlation between the six distinct anatomical regions treated and re-pigmentation grade (χ2  = 13.419, p = .009). Among these regions, facial lesions showed the best response to treatment, while the hands and feet lesions showed the poorest response. CONCLUSIONS: The clinical efficacy of 308-nm LED treatment is limited based on the treatment area. It demonstrated significant practical application in the treatment of vitiligo.

Impact of the malnutrition on mortality in Rheumatoid arthritis patients: A cohort study from NHANES 1999-2014.

Background: Patients with Rheumatoid arthritis (RA) are prone to malnutrition. However, it is rare studies assessing the relationship between malnutrition and all-cause mortality in patients with RA. Objective: To investigate the relationship between malnutrition and all-cause mortality in patients with RA in a large national sample cohort. Methods: We analyzed data on 1,976 adults ≥ 18 years of age during National Health and Nutrition Examination Survey (NHANES) 1999-2014. We chose the Controlled Nutritional Status Score (CONUT) and the Nutritional Risk Index (NRI) to assess the nutritional status of patients with RA. The Kaplan-Meier (KM) survival curves Cox proportional hazards regression models were used to analyze the associations between malnutrition and all-cause mortality. Results: Of the 1,976 patients with RA (57.38 ± 0.40 years, female 59.9%, non-Hispanic white 69.9%), the prevalence of malnutrition was 18.8% by used the CONUT and 26.6% by used the NRI. The KM survival curves showed that malnutrition was associated with a higher incidence of all-cause mortality during the 10-year follow-up period (log-rank test, P < 0.001). In the fully corrected model, the adjusting hazard ratio (aHR) for all-cause mortality in patients with moderate to severe malnutrition with CONUT and NRI were 5.63 (95% CI, 2.55-12.45; P < 0.001) and 2.56 (95% CI, 1.81-3.62; P < 0.001), respectively, compared with patients without malnutrition. Conclusion: Malnutrition is very prevalent in patients with RA, approximately 18.8% (CONUT) to 26.6% (NRI). Malnutrition is strongly associated with an increased risk of all-cause mortality. These findings underscore the importance of attention and intervention in the nutritional status of patients with RA. Further clinical trials are needed to prospectively assess the effect of nutritional interventions on the prognosis of patients with RA.

Efficacy and safety of Chinese herbal medicine Wen Xin granules for the treatment of unstable angina pectoris with Yang deficiency and blood stasis syndrome: study protocol for a randomized controlled trial.

INTRODUCTION: Unstable angina pectoris (UAP) is the common type of coronary heart disease with the risk of developing into acute myocardial infarction (AMI). Currently, there are still numerous patients suffering from recurrent angina after revascularization or conventional medication due to the microvascular lesions, endothelial dysfunction, chronic inflammation, in-stent restenosis, and other factors. As an important part of China's medical and health care system, traditional Chinese medicine (TCM) has rich clinical experience in the treatment of UAP. According to the theory of TCM, Yang deficiency and blood stasis syndrome is a common type of UAP. Wen Xin decoction, as a type of Chinese herbal medicine, has been used in the clinic for years and shown great efficacy in the treatment of UAP with Yang deficiency and blood stasis syndrome. This study aims to evaluate the efficacy and safety of Wen Xin granular in patients with UAP. METHODS AND ANALYSIS: This is a double-blinded, randomized, placebo-controlled clinical trial. A total of 502 participants will be randomly allocated to the intervention group and the placebo group. Based on conventional medication, the intervention group will be treated with Wen Xin granular and the placebo group will be treated with Wen Xin granular placebo. The primary outcomes are major adverse cardiovascular events (MACE). Assessments will be performed 1 year after the treatment. The secondary outcomes include TCM symptom scale score, Seattle angina questionnaire, and thromboelastography. Assessments will be performed at baseline (before randomization) and 4 and 8 weeks after randomization. DISCUSSION: This trial will provide high-quality data on the benefits and risks of Wen Xin granular in patients with UAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT04661709 . Registered on 30 November 2020.

Mechanistic insights into genetic susceptibility to prostate cancer.

Prostate cancer (PCa) is the second most common cancer in men and is a highly heritable disease that affects millions of individuals worldwide. Genome-wide association studies have to date discovered nearly 270 genetic loci harboring hundreds of single nucleotide polymorphisms (SNPs) that are associated with PCa susceptibility. In contrast, the functional characterization of the mechanisms underlying PCa risk association is still growing. Given that PCa risk-associated SNPs are highly enriched in noncoding cis-regulatory genomic regions, accumulating evidence suggests a widespread modulation of transcription factor chromatin binding and allelic enhancer activity by these noncoding SNPs, thereby dysregulating gene expression. Emerging studies have shown that a proportion of noncoding variants can modulate the formation of transcription factor complexes at enhancers and CTCF-mediated 3D genome architecture. Interestingly, DNA methylation-regulated CTCF binding could orchestrate a long-range chromatin interaction between PCa risk enhancer and causative genes. Additionally, one-causal-variant-two-risk genes or multiple-risk-variant-multiple-genes are prevalent in some PCa risk-associated loci. In this review, we will discuss the current understanding of the general principles of SNP-mediated gene regulation, experimental advances, and functional evidence supporting the mechanistic roles of several PCa genetic loci with potential clinical impact on disease prevention and treatment.

[Rapid discovery of tyrosinase inhibitors from Sophora flavescens:significance for comprehensive utilization of its non-medicinal resources].

Sophorae Flavescentis Radix,derived from the root of Sophora flavescens in the Leguminosae family,has been widely used in the medicine,agriculture,animal husbandry,and daily chemical industry. A pharmacophore model-based method for rapid discovery of tyrosinase inhibitors( TIs) from S. flavescens was established by molecular docking under Lipinski rules,and verified by enzyme assays. Briefly,the chemical constituent database of S. flavescens( CDSF) was established based on the previous papers. Theoptimal pharmacophore model( OPM) was constructed by DS 2019 on the basis of known active TIs. Eighty-three hits predominated by flavonoids having higher fitting scores with OPM than the positive control were screened out,and subjected to molecular docking based on the three-dimensional structure of tyrosinase crystal protein. The potential TIs such as kurarinone and nor-kurarinone were rapidly discovered from the compounds with higher docking scores than the positive control under the Lipinski rules. The results were verified by the in vitro enzyme assays. The inhibition activities of tyrosinase from non-medicinal parts of S. flavescens were also tested to explore the relationship between the inhibition activity and chemical compositions. This study is expected to provide data support for the comprehensive application and development of S. flavescens and also a new method for the rapid discovery of active substances or functional constituents in the complex systems.

Development and Validation of a Nomogram for Predicting Prognosis to Immune Checkpoint Inhibitors Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy improved the prognosis of patients with non-small cell lung cancer (NSCLC); however, reliable prognostic biomarkers are lacking. We explored factors associated with prognosis and developed a predictive model. METHODS: We retrospectively analyzed 130 consecutive stage IIIA-IVB NSCLC patients treated with ICIs combined with chemotherapy. Cox univariate and multivariate proportional hazards regression analyses were used to identify prognostic factors associated with progression-free survival (PFS). A nomogram was developed based on key factors in the training cohort (n = 86) and evaluated in the validation cohort (n = 44). According to the nomogram-based total point scores, we divided patients into low- and high-risk groups. RESULTS: In the training cohort, bone metastases (p = 0.017) and an increased derived neutrophil-to-lymphocyte ratio (p = 0.018) were significantly associated with poor PFS, while smoking (p = 0.007) and programmed death-ligand 1 (PD-L1) ≥50% (p = 0.001) were associated with improved PFS. A nomogram based on these factors was developed to predict PFS at 3, 6, and 12 months. The C-index of the nomogram to predict PFS was 0.725 (95% CI: 0.711-0.739) in the training cohort and 0.688 (95% CI: 0.665-0.711) in the validation cohort. The area under the curve (AUC) exhibited an acceptable discriminative ability, and calibration curves demonstrated a consistency between the actual results and predictions. In the training cohort, the median PFS (mPFS) was 12.3 and 5.7 months in the low- and high-risk groups, respectively (p < 0.001). In the validation cohort, the mPFS was 12.6 and 6.2 months in the low- and high-risk groups, respectively (p = 0.021). CONCLUSIONS: A predictive nomogram was developed to help clinicians assess prognosis early for advanced NSCLC patients who received ICI plus chemotherapy.

[Characteristics of Phosphorus Speciation and Genesis in Typical Tributaries of the Three Gorges Reservoir].

A comparative analysis of phosphate occurrence and its genesis during different dispatching periods of representative level I tributaries of the Three Gorges Reservoir was conducted. For this, water quality, hydrodynamic force, and environmental data were examined for backwater areas of the Xiangxi River and Shennong River during the low-water-level period (June), storage period (September) and high-water-level period (December) in 2018. The results suggest that the mass concentration of total phosphorus (TP) in the water body of the coves of Xiangxi River and Shennong River range from 0.049 mg·L-1 to 0.168 mg·L-1 and 0.059 mg·L-1 to 0.152 mg·L-1, respectively, surpassing the 0.02 mg·L-1 threshold for algal blooms. The mass concentration of TP, DP (orthophosphate), and PP (particulate phosphorus) in the coves of the tributaries were ranked as follows:storage period > high-water-level period > low-water-level period for TP; storage period > low-water-level period > high-water-level period for DP; low-water-level period > high-water-level period > storage period for PP. Based on Pearson's correlation coefficients, TP and DP were significantly correlated as well as temperature and pH, which are the key factors influencing the phosphorus in soils and sediments in the water-level-fluctuation zone. During the low-water-level and high-water-level periods of the Three Gorges Reservoir, the TP in the coves of the tributaries mainly exists as PP, accounting for more than 75% and 60%, respectively. The flow in the coves of the tributaries slows during storage periods, meaning that settlement of PP is enhanced, changing the dominance of TP to dissolved total phosphorus (DTP).

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Penetrating glassy carbon neural electrode arrays for brain-machine interfaces.

This paper presents a fabrication method for glassy carbon neural electrode arrays that combines 3D printing and chemical pyrolysis technology. The carbon electrodes have excellent biological compatibility and can be used in neural signal recording. A pretreated Si wafer is used as the substrate for 3D printing, and then, stereolithography 3D printing technology is employed to print photosensitive resin into a cone shape. Next, chemical pyrolysis is applied to convert the 3D prints into glassy carbon electrodes and modify the electrochemical performance of the carbon electrodes. Finally, the glassy carbon electrodes are packed with conductive wires and PDMS. The proposed fabrication method simplifies the manufacturing process of carbon materials, and electrodes can be fabricated without the need of deep reactive ion etching (DRIE). The height of the carbon electrodes is 1.5 mm, and the exposure area of the tips is 0.78 mm2, which is convenient for the implantation procedure. The specific capacitance of the glassy carbon arrays is higher than that of a platinum electrode (9.18 mF/cm2 vs 3.32 mF/cm2, respectively), and the impedance at 1 kHz is lower (7.1 kΩ vs 8.8 kΩ). The carbon electrodes were tested in vivo, and they showed excellent performance in neural signal recording. The signal-to-noise ratio of the carbon electrodes is 50.73 ± 6.11, which is higher than that of the Pt electrode (20.15 ± 5.32) under the same testing conditions. The proposed fabrication method of glassy carbon electrodes provides a novel approach to manufacture penetrating electrodes for nerve interfaces in biomedical engineering and microelectromechanical systems.

T follicular helper cell-mediated IL-21 production suppresses FOXP3 expression of T follicular regulatory-like cells in diffuse large B cell lymphoma patients.

Based on CD25 expression, T follicular helper cells (Tfh) could be divided into T follicular regulatory (Tfr)-like subset (CD25+CD4+CXCR5+) and CD25- Tfh subset (CD25-CD4+CXCR5+). Patients with diffuse large B cell lymphoma (DLBCL) display high level of Tfr-like cells in blood and tumor. This Tfr-like subset could suppress CD8 T cell response while promote tumor cell proliferation. In this study, we investigated the transcription factors and regulatory elements associated with Tfr-like cells in DLBCL patients. Both circulating and tumor-infiltrating Tfr-like cells presented slightly higher Blimp-1 expression and significantly higher Foxp3 expression than the CD25- Tfh subset. As the IL-2 receptor, CD25 could be moderately upregulated in stimulated CD25- Tfh cells. However, stimulated CD25- Tfh cells could not upregulate Foxp3, indicating that the distinction between Foxp3-low CD25-CXCR5+CD4+ T cells and Foxp3-high CD25+CXCR5+CD4+ T cells was not due to differences in stimulation status. Regarding cytokine production, while both Tfr-like and CD25- Tfh cells upregulated IL-21 and IL-10 during stimulation, the CD25- Tfh cells presented significantly higher IL-21 and lower IL-10 expression than the Tfr-like cells, and the TGF-ß expression was only increased in Tfr-like cells. Interestingly, IL-21 secreted from CD25- Tfh cells negatively regulated the expression of Foxp3 and IL-10 of autologous Tfr-like cells. Together, these results demonstrated that the Tfr-like and CD25- Tfh subsets of circulating Tfh cells presented different functions and should be investigated separately.