Solvated Electrons Generated on the Surface of Na-SPHI for Boosting Visible Light Photocatalytic Hydrogen Evolution with Ultra-High AQE.

Enhancing the utilization of visible-light-active semiconductors with an excellent apparent quantum efficiency (AQE) remains a significant and challenging goal in the realm of photocatalytic water splitting. In this study, a fully condensed sulfur-doped poly(heptazine imide) metalized with Na (Na-SPHI) is synthesized by an ionothermal method by using eutectic NaCl/LiCl mixture as the ionic solvent. Comprehensive characterizations of the obtained Na-SPHI reveal several advantageous features, including heightened light absorption, facilitated exciton dissociation, and expedited charge transfer. More importantly, solvated electron, powerful reducing agents, can be generated on the surface of Na-SPHI upon irradiation with visible light. Benefiting from above advantage, the Na-SPHI exhibits an excellent H2 evolution rate of 571.8 µmol·h-1 under visible light illumination and a super-high AQE of 61.7% at 420 nm. This research emphasizes the significance of the solvated electron on the surface of photocatalyst in overcoming the challenges associated with visible light-driven photocatalysis, showcasing its potential application in photocatalytic water splitting.

Multi-Scale Engineered 2D Carbon Polyhedron Array with Enhanced Electrocatalytic Performance.

Electrocatalyst engineering from the atomic to macroscopic level of electrocatalysts is one of the most powerful routes to boost the performance of electrochemical devices. However, multi-scale structure engineering mainly focuses on the range of atomic-to-particle scale such as hierarchical porosity engineering, while catalyst engineering at the macroscopic level, such as the arrangement configuration of nanoparticles, is often overlooked. Here, a 2D carbon polyhedron array with a multi-scale engineered structure via facile chemical etching, ice-templating induced self-assembly, and high-temperature pyrolysis processes is reported. Controlled phytic acid etching of the carbon precursor introduces homogeneous atomic phosphorous and nitrogen doping, as well as a well-defined mesoporous structure. Subsequent ice-templated self-assembly triggers the formation of a 2D particle array superstructure. The atomic-level doping gives rise to high intrinsic activity, while the well-engineered porous structure and particle arrangement addresses the mass transport limitations at the microscopic particle level and macroscopic electrode level. As a result, the as-prepared electrocatalyst delivers outstanding performance toward oxygen reduction reaction in both acidic and alkaline media, which is better than recently reported state-of-the-art metal-free electrocatalysts. Molecular dynamics simulation together with extensive characterizations indicate that the performance enhancement originates from multi-scale structural synergy.

Pre-Coordination Induced Further Deamination to Create Inter-Chain Cross-Linking in Carbon Nitride for Enhanced Photocatalytic H2O2 Production.

Creating cross-linking to establish efficient inter-chain charge-transfer channels in carbon nitride represents a promising strategy for enhancing its photocatalytic capabilities. Molten salt-assisted calcining has emerged as a method for preparing cross-linked carbon nitrides. However, the precise influence of molten salts on the molecular structure of carbon nitride remains to be fully elucidated. Herein, we develop a KCl guided cross-linking reaction to preliminarily reveal the formation mechanism of cross-linking. The cross-linking reaction is initiated by the pre-coordination of amino groups with K+. Subsequent heating at high temperature converts the amino groups into chlorines. Then, dechlorination leads to the formation of cross-linking. Thus, this cross-linking reaction can be accurately described as a pre-coordination-induced, two-step deamination reaction. The pre-coordination step plays a pivotal role in the cross-linking process. Sufficient pre-coordination results in a relatively high cross-linking degree of the as-prepared CNK-2. Consequently, CNK-2 demonstrates a significantly enhanced photocatalytic H2O2 production, with a generation rate of 682 µmol L-1 h-1, about 59 times that of traditional carbon nitride.

Enhanced Interface Charge Carrier Transport of SnO2/CeO2 via Oxygen Vacancy Synergized Heterojunction for Triethylamine Sensing Property.

Efficient charge carrier transport characteristics are critical to achieving the excellent performance of metal-oxide semiconductor gas sensors. Herein, SnO2/CeO2 heterojunction layered nanosheets with abundant oxygen vacancies were successfully synthesized through a simple solvothermal assisted high-temperature calcination method. The synergistic effect of oxygen vacancies and heterojunctions promoting the charge carrier transport properties at the SnO2/CeO2 interface for the enhanced sensing properties of triethylamine (TEA) was highlighted. As a result, the optimized SnO2/CeO2 exhibits improved gas sensing performance at 173 °C to 50 ppm of TEA. These include high response (205), excellent selectivity, low detection limit, and good long-term stability. This enhanced gas sensing property of SnO2/CeO2 is mainly attributed to the fact that the heterojunction and oxygen vacancies act as dual active sites synergistically inducing electron transfer, thereby effectively modulating the transport properties of the interfacial charge carriers, and thus facilitate the surface reactions efficiently. In this work, the dual-engineering strategy of synergistic interaction of heterojunction and oxygen vacancies can provide new perspectives for the design of advanced gas sensing materials.

INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-γ signaling.

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

GFPBW1, a ß-glucan from Grifola frondosa as vaccine adjuvant: APCs activation and maturation.

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

Exploring the behavioral intentions of PICC-related thrombosis prevention in breast cancer patients undergoing chemotherapy: a qualitative study based on theory of planned behavior.

PURPOSE: To explore the behavioral intention of breast cancer patients undergoing chemotherapy to prevent PICC-related thrombosis based on the theory of planned behavior (TPB). METHODS: This qualitative study employed purposive sampling and conducted semi-structured interviews with 14 breast cancer patients undergoing chemotherapy in the outpatient chemotherapy ward of a tertiary A-level comprehensive hospital in Beijing from July to August 2023. Data were analyzed using Colaizzi's descriptive analysis framework. RESULTS: Data analysis identified 10 themes that were derived from 4 aspects. Regarding behavioral attitude, three themes were condensed: (1) Considering the benefits of preventive measures, (2) Simple and easy preventive measures, and (3) Underestimating the importance of PICC-related thrombosis prophylaxis. Subjective norms yielded two main themes and five sub-themes: (1) Support from those close to the patient motivates adherence to prophylaxis (support from the patient's family, healthcare professionals, and other patients) and (2) Patients are influenced by personal factors to form an internal driving force (physical symptoms, fear of PICC-related thrombosis). Regarding perceived behavioral control, three main themes and four sub-themes were extracted: (1) Obstacles before actual prevention exercise (prevention information, hard-to-remember information), (2) Forgetfulness is the main obstacle factor, and (3) Wanting to overcome barriers to adhere to regular prevention (confidence to overcome obstacles, hope to get support). CONCLUSIONS: The impediments and facilitators identified in this study may provide a scientific foundation for subsequent targeted non-pharmacological preventive interventions for PICC-related thrombosis based on TPB in breast cancer patients undergoing chemotherapy. Special interventions should be designed for the patients in three areas: the patients themselves, the supporters around the patient, and the healthcare professionals.

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Association between Neonatal Outcomes and Admission Hypothermia among Very Preterm Infants in Chinese Neonatal Intensive Care Units: A Multicenter Cohort Study.

OBJECTIVE: We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. STUDY DESIGN: This retrospective cohort study enrolled infants with 240/7 to 316/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. RESULTS: A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9-100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5-37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15-1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0-36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09-1.83) and 1.93 (95% CI, 1.31-2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. CONCLUSION: Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. KEY POINTS: · Admission hypothermia is common in VPIs.. · The incidence of admission hypothermia in VPIs remains high in China.. · Admission hypothermia is associated with adverse outcomes in VPIs..

Spatio-temporal variation of bacterial community structure in two intertidal sediment types of Jiaozhou Bay.

The intertidal sediment environment is dynamic and the biofilm bacterial community within it must constantly adapt, but an understanding of the differences in the biofilm bacterial community within sediments of different types is still relatively limited. The semi-enclosed Jiaozhou Bay has a temperate monsoon climate, with strong currents at the mouth of the bay. In this study, the structure of the bacterial community in Jiaozhou Bay sediment biofilms are described using high-throughput 16 S rRNA gene sequencing and the effects of temporal change and different sediment environment types are discussed. Alpha diversity was significantly higher in sandy samples than in muddy samples. Sandy sediments with increased heterogeneity promote bacterial aggregation. Beta diversity analysis showed significant differences between sediment types and between stations. Proteobacteria and Acidobacteria were significantly more abundant at ZQ, while Campilobacterota was significantly more abundant at LC. The relative abundances of Bacteroidetes, Campilobacterota, Firmicutes, and Chloroflexi were significantly higher in the muddy samples, while Actinobacteria and Proteobacteria were higher in the sandy samples. There were different phylum-level biomarkers between sediment types at different stations. There were also different patterns of functional enrichment in biogeochemical cycles between sediment types and stations with the former having more gene families that differed significantly, highlighting their greater role in determining bacterial function. Bacterial amplicon sequence variant variation between months was less than KEGG ortholog variation between months, presumably the temporal change had an impact on shaping the intertidal sediment bacterial community, although this was less clear at the gene family level. Random forest prediction yielded a combination of 43 family-level features that responded well to temporal change, reflecting the influence of temporal change on sediment biofilm bacteria.

Perinatal characteristics and neonatal outcomes of singletons and twins in Chinese very preterm infants: a cohort study.

BACKGROUND: The prevalence of preterm birth has been rising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China. METHODS: The study population comprised all infants born before 32 weeks in the Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Three-level and population-average generalized estimating equation (GEE)/alternating logistic regression (ALR) models were used to determine the association of twins with neonatal morbidities and the use of NICU resources. RESULTS: During the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weights of 1333.70 g and 1294.63 g, respectively. Twins were significantly more likely to be delivered by caesarean section (p < 0.01), have antenatal steroid usage (p = 0.048), have been conceived by assisted reproductive technology (ART) (p < 0.01), have a higher prevalence of maternal diabetes (p < 0.01) and be inborn (p < 0.01) than singletons. In addition, twins had a lower prevalence of small for gestational age, maternal hypertension, and primigravida mothers than singletons (all p < 0.01). After adjusting for potential confounders, twins had higher mortality rates (adjusted odds ratio [AOR] 1.28, 95% confidence interval [CI] 1.10-1.49), higher incidences of short-term composite outcomes (AOR 1.28, 95% CI 1.09-1.50), respiratory distress syndrome (RDS) (AOR 1.30, 95% CI 1.12-1.50), and bronchopulmonary dysplasia (BPD) (AOR 1.10, 95% CI 1.01-1.21), more surfactant usage (AOR 1.22, 95% CI 1.05-1.41) and prolonged hospital stays (adjusted mean ratio 1.03, 95% CI 1.00-1.06), compared to singletons. CONCLUSION: Our work suggests that twins have a greater risk of mortality, a higher incidence of RDS and BPD, more surfactant usage, and longer NICU stays than singletons among VPIs in China.

Delta large-channel technique versus microscopy-assisted laminar fenestration decompression for lumbar spinal stenosis: a one-year prospective cohort study.

PURPOSE: When it comes to treating lumbar spinal stenosis (LSS), a procedure known as microscope-assisted fenestration decompression has expediently become the gold standard. With the advancement of spinal endoscopy, the Delta large-channel approach has shown promising clinical outcomes in the management of lumbar spinal stenosis. However, case studies of this method being used to treat lumbar spinal stenosis are still uncommon. The purpose of this research was to examine how well microscopy-assisted laminectomy and the Delta large-channel approach work in treating LSS in the clinic. METHODS: From May 2018 to June 2020, 149 patients diagnosed with LSS were divided into 80 patients in Delta large-channel technique groups (FE group) and 69 patients in microscope groups (Micro group). Lower back and lower limb pain were measured using the visual analogue scale (VAS-LBP and VAS-LP), while lower limb numbness was evaluated using the 11-point numerical rating scale (NRS-LN); modified Oswestry Disability Index (ODI) was used to evaluate the quality of life, and modified MacNab criteria were used to assess the clinical efficacy before surgery and at one week, three months, six months, and 12 months after surgery. All patients had single-level lumbar spinal stenosis, and clinical data such as hospital stay, operation time, intraoperative blood loss were statistically analyzed. RESULTS: Finally, 111 patients (62 in FE group and 49 in Micro group) completed follow-up. Compared with preoperative results, postoperative VAS-LBP, VAS-LP, NRS-LN score and modified ODI score were significantly improved in 2 groups (P < 0.05), but there was no significant difference in postoperative follow-up at each time point (P > 0.05), Except 1 week after surgery, VAS-LBP in FE group was lower than that in Micro group (P < 0.05). It is noteworthy that the FE group had a shorter hospital stay, less intraoperative blood loss, and a quicker time of getting out of bed when compared with the microscope group，but the operation time was just the opposite (P < 0.05). The excellent and good rate was 83.87% in FE group and 85.71% in Micro group (P > 0.05). CONCLUSIONS: Both microscope-assisted laminar fenestration decompression and Delta large-channel procedures provide satisfactory treatment outcomes, however the Delta large-channel approach has some potential advantages for the treatment of LSS, including quicker recovery and sooner reduced VAS-LBP. Long-term consequences, however, will necessitate additional follow-up and research.

The influence of male and female overweight/obesity on IVF outcomes: a cohort study based on registration in Western China.

BACKGROUND: Overweight/obesity can affect fertility, increase the risk of pregnancy complications, and affect the outcome of assisted reproductive technology (ART). However, due to confounding factors, the accuracy and uniformity of published findings on IVF outcomes have been disputed. This study aimed to assess the effects of both male and female body mass index (BMI), individually and in combination, on IVF outcomes. METHODS: This retrospective cohort study included 11,191 couples undergoing IVF. Per the Chinese BMI standard, the couples were divided into four groups: normal; female overweight/obesity; male overweight/obesity; and combined male and female overweight/obesity. The IVF outcomes of the four groups were compared and analysed. RESULTS: Regarding the 6569 first fresh IVF-ET cycles, compared with the normal weight group, the female overweight/obesity and combined male/female overweight/obesity groups had much lower numbers of available embryos and high-quality embryos (p < 0.05); additionally, the fertilization (p < 0.001) and normal fertilization rates (p < 0.001) were significantly decreased in the female overweight/obesity group. The combined male/female overweight/obesity group had significant reductions in the available embryo (p = 0.002), high-quality embryo (p = 0.010), fertilization (p = 0.001) and normal fertilization rates (p < 0.001); however, neither male or female overweight/obesity nor their combination significantly affected the clinical pregnancy rate (CPR), live birth rate (LBR) or abortion rate (p > 0.05). CONCLUSION: Our findings support the notion that overweight/obesity does not influence pregnancy success; however, we found that overweight/obesity affects the fertilization rate and embryo number and that there are sex differences.

Trends in Acupuncture Therapy in Cardiovascular Disease: A Bibliometric Analysis.

Purpose: Acupuncture has been used for almost half a century to treat and prevent cardiovascular (CV) problems. However, most of its effects are poorly understood, and there are few studies based on bibliometric analysis of the general trends in acupuncture therapy in cardiovascular disorders (CVD). Thus, we aimed to show the present state and trends in this sector during the last few years. Methods: Articles were obtained from the Web of Science Core Collection (WOSCC) from its inception to May 30, 2021. The acquired information from the articles was analyzed by The Online Bibliometric Analysis Platform website (https://bibliometric.com), Citespace and VOSviewer in respective form in order to assess and forecast the hottest areas and trends in this field. Results: The final analysis included a total of 384 articles and reviews. Over the years, the number of publications has gradually increased. The United States and University of California Irvine were the country and institution that contributed the most to the field. John C Longhurst was the most productive author; Li P the most cited author. Co-occurrence analysis revealed 5 branches (including acupuncture, blood pressure, electroacupuncture, stimulation, cardiovascular responses) and 12 clusters. Recent keyword bursts included "reflex," "arcuate nucleus," "electroacupuncture," "cardiovascular disease" and "hypertension." Conclusion: Yearly publications continue to increase every decade, indicating a bright future in this scientific field. Acupuncture's function in CVD is a future study priority.

Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum.

Immunogenicity is a major issue associated with the PK, efficacy, and safety evaluation of therapeutic protein products during pre-clinical and clinical studies. A multi-tiered approach consisting of screening, confirmatory, and titration assays has been widely adopted for anti-drug antibody testing. GQ1001, a recombinant humanized anti-human epidermal growth factor receptor 2 monoclonal antibody covalently linked to a cytotoxin of DM1, possesses a novel format of antibody-drug conjugates. In this study, we reported the development, validation, and application of an acid-dissociation bridging enzyme-linked immunosorbent assay for the detection of antibodies against GQ1001 in cynomolgus monkey serum. The sensitivity of the screening assay was 126.141 ng/mL in undiluted serum. The screening assay and confirmatory assay were neither affected by the naïve monkey serum nor by 2% and 5% (v/v) erythrocyte hemolysates. Moreover, the assay was not subject to interference by 2500 ng/mL of human IgG1 in the samples. Drug interference at low positive control (150 ng/mL) and high positive control (8000 ng/mL) of anti-GQ1001 antibodies was not observed when GQ1001 concentrations were below 3.125 µg/mL and 100 µg/mL, respectively. Furthermore, no hook effect was observed for the positive antibodies in the concentration range of 8 to 64 µg/mL. The validated assay was, thereafter, successfully applied to a single-dose toxicity study of GQ1001. Anti-drug antibody positive rates among dosing animals and testing samples were reported, and no significant impact was found on toxicokinetic outcomes.

Two-Dimensional Metal-Organic Framework Superstructures from Ice-Templated Self-Assembly.

Here, we report the synthesis of two-dimensional (2D) layered metal-organic framework (MOF) nanoparticle (NP) superstructures via an ice-templating strategy. MOF NP monolayers and bilayers can be obtained by regulating the concentration of colloidal MOF NPs without any external fields during self-assembly. Adjacent polyhedral MOF NPs are packed and aligned through crystalline facets, resulting in the formation of a quasi-ordered array superstructure. The morphology of the MOF layers is well preserved when subjected to pyrolysis, and the obtained carbon NPs have hollow interiors driven by the outward contraction of MOF precursors during pyrolysis. With the advantages of large surface areas, hierarchical porosity, high exposure of active sites, and fast electron transport of the 2D layered structure, the mono- and bilayered carbon NP superstructures show better oxygen reduction activity than isolated carbon particles in alkaline media. Our work demonstrates that ice-templating is a powerful strategy to fabricate superstructures of various MOFs and their derivatives.

PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1.

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.

New laboratory evidence for the association between endothelial dysfunction and COVID-19 disease progression.

There is growing evidence that angiotensin-converting enzyme 2 is highly expressed on endothelial cells, endothelial dysfunction plays a critical role in coronavirus disease 2019 (COVID-19) progression, but laboratory evidence is still lacking. This study established a multicenter retrospective cohort of 966 COVID-19 patients from three hospitals in Wuhan, China. We found that male (62.8% vs. 46.5%), old age [72 (17) vs. 60.5 (21)], and coexisting chronic diseases (88.5% vs. 60.0%) were associated with poor clinical prognosis in COVID-19. Furthermore, the deteriorated patients exhibited more severe multiorgan damage, coagulation dysfunction, and extensive inflammation. Additionally, a cross-sectional study including 41 non-COVID-19 controls and 39 COVID-19 patients assayed endothelial function parameters in plasma and showed that COVID-19 patients exhibited elevated vascular cell adhesion molecule-1 (VCAM-1) (median [IQR]: 0.32 [0.27] vs. 0.17 [0.11] µg/ml, p < 0.001), E-selectin (21.06 [12.60] vs. 11.01 [4.63] ng/ml, p < 0.001), tissue-type plasminogen activator (tPA) (0.22 [0.12] vs. 0.09 [0.04] ng/ml, p < 0.001), and decreased plasminogen activator inhibitor-1 (0.75 [1.31] vs 6.20 [5.34] ng/ml, p < 0.001), as compared to normal controls. Moreover, VCAM-1 was positively correlated with d-dimer (R = 0.544, p < 0.001); tPA was positively correlated with d-dimer (R = 0.800, p < 0.001) and blood urea nitrogen (R = 0.638, p < 0.001). Our findings further confirm the strong association between endothelial dysfunction and poor prognosis of COVID-19, which offers a rationale for targeting endothelial dysfunction as a therapeutic strategy for COVID-19.

Nomogram for stratifying patients with lifelong premature ejaculation before using the PHQ-9: An observational study.

OBJECTIVE: A PHQ-9 score ≥ 15, represented as PHQ-9+ , indicates major depressive disorder (MDD). On using PHQ-9, the psychological burden of several patients with lifelong premature ejaculation (LPE) gets aggravated, which may lead to LPE development. We aim to construct a nomogram for predicting the individual risk of PHQ-9+ in patients with LPE and discerning those with low risks, who should avoid the PHQ-9. METHODS: The nomogram was constructed by analysing data of 802 patients from Xijing Hospital and Northwest Women's & Children's Hospital. The LASSO and multivariable logistic regressions were used to identify independent predictors of PHQ-9+ , used for developing the nomogram. The discrimination, calibration and clinical usefulness of the nomogram were assessed in the derivation cohort and an independent validation cohort, which was composed of 505 prospectively enrolled patients from Daxing Hospital and Xijing Hospital. RESULTS: The duration of PE, IELT, a history of PE exacerbation, IIEF-5 score, urinary frequency and physical pain score were identified as independent predictors. The nomogram showed excellent calibration, discrimination and clinical usefulness in the derivation and validation cohorts, with a predictive accuracy of 0.781 and 0.763, respectively. Based on this nomogram, patients were divided into not recommended, recommended and strongly recommended PHQ-9 filling groups, with PHQ-9+ rates of 3.5%, 9.3% and 30.7%, respectively. CONCLUSION: A nomogram to discern LPE patients with low risks of PHQ-9+ was established. This tool can increase the positivity of MDD screening and may improve the therapeutic outcomes of those in the low-risk group.

Association between hospital and ICU structural factors and patient outcomes in China: a secondary analysis of the National Clinical Improvement System Data in 2019.

BACKGROUND: Hospital and ICU structural factors are key factors affecting the quality of care as well as ICU patient outcomes. However, the data from China are scarce. This study was designed to investigate how differences in patient outcomes are associated with differences in hospital and ICU structure variables in China throughout 2019. METHODS: This was a multicenter observational study. Data from a total of 2820 hospitals were collected using the National Clinical Improvement System Data that reports ICU information in China. Data collection consisted of a) information on the hospital and ICU structural factors, including the hospital type, number of beds, staffing, among others, and b) ICU patient outcomes, including the mortality rate as well as the incidence of ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs). Generalized linear mixed models were used to analyse the association between hospital and ICU structural factors and patient outcomes. RESULTS: The median ICU patient mortality was 8.02% (3.78%, 14.35%), and the incidences of VAP, CRBSI, and CAUTI were 5.58 (1.55, 11.67) per 1000 ventilator days, 0.63 (0, 2.01) per 1000 catheter days, and 1.42 (0.37, 3.40) per 1000 catheter days, respectively. Mortality was significantly lower in public hospitals (ß = - 0.018 (- 0.031, - 0.005), p = 0.006), hospitals with an ICU-to-hospital bed percentage of more than 2% (ß = - 0.027 (- 0.034, -0.019), p < 0.001) and higher in hospitals with a bed-to-nurse ratio of more than 0.5:1 (ß = 0.009 (0.001, 0.017), p = 0.027). The incidence of VAP was lower in public hospitals (ß = - 0.036 (- 0.054, - 0.018), p < 0.001). The incidence of CRBSIs was lower in public hospitals (ß = - 0.008 (- 0.014, - 0.002), p = 0.011) and higher in secondary hospitals (ß = 0.005 (0.001, 0.009), p = 0.010), while the incidence of CAUTIs was higher in secondary hospitals (ß = 0.010 (0.002, 0.018), p = 0.015). CONCLUSION: This study highlights the association between specific ICU structural factors and patient outcomes. Modifying structural factors is a potential opportunity that could improve patient outcomes in ICUs.