Efficient Solar-Driven Water Splitting Enabled by Perovskite Photovoltaics and a Halogen-Modulated Metal-Organic Framework Electrocatalyst.

Solar-driven water splitting powered by photovoltaics enables efficient storage of solar energy in the form of hydrogen fuel. In this work, we demonstrate efficient solar-to-hydrogen conversion using perovskite (PVK) tandem photovoltaics and a halogen-modulated metal-organic framework (MOF) electrocatalyst. By substituting tetrafluoroterephthalate (TFBDC) for terephthalic (BDC) ligands in a nickel-based MOF, we achieve a 152 mV improvement in oxygen evolution reaction (OER) overpotential at 10 mA·cm2. Through X-ray photoelectron spectroscopy (XPS), X-ray adsorption structure (XAS) analysis, theoretical simulation, and electrochemical results, we demonstrated that the introduction of fluorine atoms enhanced the intrinsic activity of Ni sites as well as the transfer property and accessibility of the MOF. Using this electrocatalyst in a bias-free photovoltaic electrochemical (PV-EC) system with a PVK/organic tandem solar cell, we achieve 6.75% solar-to-hydrogen efficiency (ηSTH). We also paired the electrocatalyst with a PVK photovoltaic module to drive water splitting at 206.7 mA with ηSTH of 10.17%.

Knowledge and attitudes of medical and pharmacy students about pharmacogenomics: a systematic review and meta-analysis.

Pharmacogenomics (PGx) is rapidly growing branch of molecular genetics with high potentials to influence therapeutics. This review evaluates knowledge and attitudes of medical and pharmacy students about PGx. A literature search was conducted in electronic databases and studies were selected by following precise eligibility criteria. After quality assessment, studies were reviewed systematically, and meta-analyses of proportions were performed to estimate response rates of students. Fifteen studies (5509 students; 69% [95% confidence interval (CI): 60%, 77%] females) were included. Among students, 28% [95%CI: 12, 46] had adequate PGx knowledge; 65% [95%CI: 55, 75] were willing to have PGx test for their own risk assessment; 78% [95%CI: 71, 84] had intention to incorporate PGx in future practice; and 32% [95%CI: 21, 43] were satisfied with current PGx component of curriculum. Age, advanced year of educational program, and more time spent in PGx education were positively associated with PGx knowledge and positive attitudes.

Molecular Engineering of Metal-Organic Frameworks as Efficient Electrochemical Catalysts for Water Oxidation.

Metal-organic framework (MOF) solids with their variable functionalities are relevant for energy conversion technologies. However, the development of electroactive and stable MOFs for electrocatalysis still faces challenges. Here, a molecularly engineered MOF system featuring a 2D coordination network based on mercaptan-metal links (e.g., nickel, as for Ni(DMBD)-MOF) is designed. The crystal structure is solved from microcrystals by a continuous-rotation electron diffraction (cRED) technique. Computational results indicate a metallic electronic structure of Ni(DMBD)-MOF due to the Ni-S coordination, highlighting the effective design of the thiol ligand for enhancing electroconductivity. Additionally, both experimental and theoretical studies indicate that (DMBD)-MOF offers advantages in the electrocatalytic oxygen evolution reaction (OER) over non-thiol (e.g., 1,4-benzene dicarboxylic acid) analog (BDC)-MOF, because it poses fewer energy barriers during the rate-limiting *O intermediate formation step. Iron-substituted NiFe(DMBD)-MOF achieves a current density of 100 mA cm-2 at a small overpotential of 280 mV, indicating a new MOF platform for efficient OER catalysis.

Dioscin induces M1 macrophage polarization through Connexin-43 Channels in Tumor-associated-macrophages-mediated melanoma metastasis.

BACKGROUND: Tumor-associated macrophages (TAMs) are important constituent parts of tumor microenvironment that connected with tumor metastasis in melanoma. Connexin 43 (Cx43) was expressed in all the immune cells which modulated different aspects of immune response. However, the concrete molecular mechanism maintains unclear. PURPOSE: The study aimed to find a natural drug monomer effectively reversed the polarity of tumor-associated macrophages inhibiting melanoma metastasis and improving survival time. METHODS: Flow cytometry was used to determine the effects of dioscin on the macrophage phenotype. Western bolt and ELISA were performed to explore the underlying mechanism of dioscin and a co-culture experiment in vitro was applied to assess the role of dioscin on TAMs-mediated melanoma proliferation, invasion and migration. Moreover, in vivo melanoma metastasis models were established for examining effects of dioscin on TAMs-mediated melanoma metastasis. RESULTS: Dioscin repolarized macrophages from M2 towards M1-like phenotype. Dioscin suppressed M2-like phenotype macrophages through enhanced the expression and transport function of Cx43. Furthermore, the stimulation IFN-γ/STAT1 pathway and suppression IL-4/JAK2/STAT3 pathway were major mechanism of dioscin. Importantly, dioscin suppressed Cx43G21R mutation TAMs induced proliferation, invasion, migration and metastasis of melanoma cells. It worthily noting that dioscin ameliorated tumor-associated-macrophages-mediated melanoma metastasis in vitro and vivo. CONCLUSION: Dioscin re-polarized macrophages from M2 to M1 phenotype through activation of Cx43-gap-junction-intercellular-communications (Cx43-GJs)/IFN-γ/STAT1 pathway and inhibition of Cx43-GJs/IL-4/JAK2/STAT3 suppressing migration, invasion and metastasis of melanoma, which provided a theoretical and experimental basis for treating melanoma metastasis.

Clinical characteristics and risk factors for a prolonged length of stay of patients with asymptomatic and mild COVID-19 during the wave of Omicron from Shanghai, China.

BACKGROUND: This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant. METHODS: A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8-10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis. RESULTS: The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS. CONCLUSIONS: Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.

Freestanding 2D NiFe Metal-Organic Framework Nanosheets: Facilitating Proton Transfer via Organic Ligands for Efficient Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) is crucial to electrochemical hydrogen production. However, designing and fabricating efficient electrocatalysts still remains challenging. By confinedly coordinating organic ligands with metal species in layered double hydroxides (LDHs), an innovative LDHs-assisted approach is developed to facilely synthesize freestanding bimetallic 2D metal-organic framework nanosheets (2D MOF NSs), preserving the metallic components and activities in OER. Furthermore, the research has demonstrated that the incorporation of carboxyl organic ligands coordinated with metal atoms as proton transfer mediators endow 2D MOF NSs with efficient proton transfer during the electrochemical OHads  â†’ Oads transition. These freestanding NiFe-2D MOF NSs require a small overpotential of 260 mV for a current density of 10 mA cm-2 . When this strategy is applied to LDH nanosheets grown on nickel foam, the overpotential can be reduced to 221 mV. This outstanding OER activity supports the capability of multimetallic organic frameworks for the rational design of water oxidation electrocatalysts. This strategy provides a universal path to the synthesis of 2D MOF NSs that can be used as electrocatalysts directly.

Prognostic value and predictive biomarkers of phenotypes of tumour-associated macrophages in colorectal cancer.

BACKGROUND: The roles of different subtypes of tumour-associated macrophages (TAMs) in predicting the prognosis of colorectal cancer (CRC) remain controversial. In this study, different subtypes of TAMs were investigated as prognostic and predictive biomarkers for CRC. METHODS: Expressions of CD68, CD86 and CD163 were investigated by immunohistochemistry (IHC) and immunofluorescence (IF), and the correlation between the expression of CD86 and CD163 was calculated in colorectal cancer tissues from 64 CRC patients. RESULTS: The results showed that high expressions of CD86+ and CD68+ CD86+ TAMs as well as low expression of CD163+ and CD68+ CD163+ TAMs were significantly associated with favourable overall survival (OS). The level of CD86 protein expression showed a negative correlation with CD163 protein expression. In addition, CD86 protein expression remarkably negatively correlated with tumour differentiation and tumour node metastasis (TNM) stage, while CD163 protein expression significantly positively correlated with tumour differentiation and tumour size. As an independent risk factor, high expression of CD86 TAMs had prominently favourable prognostic efficacy, while high expression of CD68+ CD163+ TAMs had significantly poor prognostic efficacy. CONCLUSIONS: These results indicate that CD86+ and CD68+ CD163+ TAMs as prognostic and predictive biomarkers for CRC.

Surface engineered CoP/Co3O4 heterojunction for high-performance bi-functional water splitting electro-catalysis.

In the electrochemical water splitting process, integrating hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in the same electrolyte with the same catalyst is highly beneficial for increasing the energy efficiency and reducing the fabrication cost. However, most OER catalysts are unstable in the acidic solution, while HER shows poor kinetics in the alkaline solution, which hinders the scale-up application of electro-catalytic water splitting. In this work, a CoP/Co3O4 heterostructure is firstly fabricated and then O and P defects are introduced via surface engineering (s-CoP/Co3O4). The as-prepared material was employed as the catalyst towards electrochemical water splitting in an alkaline environment. In alkaline HER, a current density of -10 mA cm-2 can be achieved at an overpotential of 106 mV vs. RHE. In the OER process, the overpotential of s-CoP/Co3O4 electrode is only 211 mV vs. RHE at 10 mA cm-2 in 1 M KOH, and the corresponding Tafel slope is only 58.4 mV dec-1 so that the s-CoP/Co3O4 electrode could be used as the bifunctional catalyst for alkaline water splitting. This work provides a simple and low-cost approach to fabricate a Co-based heterojunction electrode with unsaturated metal sites to improve the electro-catalytic activities towards water splitting.

Exploring the Mechanism of Action of Herbal Medicine (Gan-Mai-Da-Zao Decoction) for Poststroke Depression Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Poststroke depression (PSD) is the most common and serious neuropsychiatric complication occurring after cerebrovascular accidents, seriously endangering human health while also imposing a heavy burden on society. Nevertheless, it is difficult to control disease progression. Gan-Mai-Da-Zao Decoction (GMDZD) is effective for PSD, but its mechanism of action in PSD is unknown. In this study, we explored the mechanism of action of GMDZD in PSD treatment using network pharmacology and molecular docking. Material and methods. We obtained the active components of all drugs and their targets from the public database TCMSP and published articles. Then, we collected PSD-related targets from the GeneCards and OMIM databases. Cytoscape 3.8.2 was applied to construct PPI and composite target disease networks. In parallel, the DAVID database was used to perform GO and KEGG enrichment analyses to determine the biological processes enriched in the treatment-related drugs in vivo. Finally, molecular docking was used to verify the association between the main active ingredients and their targets. RESULTS: The network pharmacological analysis of GMDZD in PSD revealed 107 active ingredients with important biological effects, including quercetin, luteolin, kaempferol, naringenin, and isorhamnetin. In total, 203 potential targets for the treatment of this disease were screened, including STAT3, JUN, TNF, TPT53, AKT1, and EGFR. These drugs are widely enriched in a series of signaling pathways, such as TNF, HIF-1, and toll-like receptor. Moreover, molecular docking analysis showed that the core active components were tightly bound to their core targets, further confirming their anti-PSD effects. CONCLUSION: This prospective study was based on the integrated analysis of large data using network pharmacology technology to explore the feasibility of GMDZD for PSD treatment that was successfully validated by molecular docking. It reflects the multicomponent and multitarget characteristics of Chinese medicine and, more importantly, brings hope for the clinical treatment of PSD.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of COVID-19: a multicenter retrospective cohort study of 4086 cases in China.

To establish an effective nomogram for predicting in-hospital mortality of COVID-19, a retrospective cohort study was conducted in two hospitals in Wuhan, China, with a total of 4,086 hospitalized COVID-19 cases. All patients have reached therapeutic endpoint (death or discharge). First, a total of 3,022 COVID-19 cases in Wuhan Huoshenshan hospital were divided chronologically into two sets, one (1,780 cases, including 47 died) for nomogram modeling and the other (1,242 cases, including 22 died) for internal validation. We then enrolled 1,064 COVID-19 cases (29 died) in Wuhan Taikang-Tongji hospital for external validation. Independent factors included age (HR for per year increment: 1.05), severity at admission (HR for per rank increment: 2.91), dyspnea (HR: 2.18), cardiovascular disease (HR: 3.25), and levels of lactate dehydrogenase (HR: 4.53), total bilirubin (HR: 2.56), blood glucose (HR: 2.56), and urea (HR: 2.14), which were finally selected into the nomogram. The C-index for the internal resampling (0.97, 95% CI: 0.95-0.98), the internal validation (0.96, 95% CI: 0.94-0.98), and the external validation (0.92, 95% CI: 0.86-0.98) demonstrated the fair discrimination ability. The calibration plots showed optimal agreement between nomogram prediction and actual observation. We established and validated a novel prognostic nomogram that could predict in-hospital mortality of COVID-19 patients.

A simple paper-based colorimetric analytical device for rapid detection of Enterococcus faecalis under the stress of chlorophenols.

Bacteria detection and toxicity measurement are essential in many aspects. Becoming increasingly popular in recent years, paper-based analytical devices (PADs) have proven to be cost-effective, portable and eco-friendly with quantitative diagnostic results. In this work, by a straightforward soaking-drying method, a resazurin-deposited PAD has been developed for rapid bacteria detection and biotoxicity measurement. The colorimetric response on the PAD was generated from metabolic reduction of resazurin by Enterococcus faecalis, a facultative anaerobic bacterial strain. After recording and quantifying the colorimetric response with Hue value by a smartphone, the bioassay on PAD enables the detection of resazurin reduction kinetics difference among bacteria at various densities in 10 min. Thereby, the bioassay on PAD was applied to study the toxicity of two chlorophenols, i.e. pentachlorophenol (PCP) and 4-chlorophenol (4-CP), to E. faecalis. Compared to growth-based inhibition test, which takes 5 h, this assay shows higher efficiency, i.e. in 30 min, the biotoxicity difference between PCP and 4-CP can be identified.

High Current Enabled Stable Lithium Anode for Ultralong Cycling Life of Lithium-Oxygen Batteries.

Rechargeable lithium-oxygen (Li-O2) batteries (LOBs) with extremely high theoretical energy density have been regarded as a promising next-generation energy storage technology. However, the limited cycle life, undesirable corrosion, and safety hazards are seriously limiting the practical application of the lithium metal anode in LOBs. Here, we demonstrate a rational design of the Li-Al alloy (LiAlx) anode that successfully achieves ultralong cycling life of LOBs with stable Li cycling. Through in situ high-current pretreatment technology, Al atoms accumulates, and a stable Al2O3-containing solid electrolyte interphase protective film formed on the LiAlx anode surface to suppress side reactions and O2 crossover. The cycling life of LOB with the protected LiAlx anode increases to 667 cycles under a fixed capacity of 1000 mA h g-1, as compared to 17 cycles without pretreatment. We believe that this in situ high-current pretreatment strategy presents a new vision to protect the lithium-containing alloy anodes, such as Li-Al, Li-Mg, Li-Sn, and Li-In alloys for stable and safe lithium metal batteries (Li-O2 and Li-S batteries).

High efficient adsorption and storage of iodine on S, N co-doped graphene aerogel.

High efficient adsorption of radioiodine in nuclear waste has attracted extensive attentions all over the world. In this work, we fabricated sulfur and nitrogen co-doped graphene aerogels (SN-GA) through one-step hydrothermal method, and investigated its iodine adsorption behavior including adsorption kinetics and isotherms in water. Our results reveal that SN-GA exhibits a 3D porous architecture with thiophene-S, oxidized-S, pyridine-N, pyrrole-N and graphite-N co-doped into the sp2 carbon frameworks. The adsorption experiment showed SN-GA has a maximum iodine adsorption capacity of 999 mg g-1 determined by Langmuir isotherm, and the adsorption process could be better described by the pseudo-second-order model.

Lithium Dendrite Suppression and Enhanced Interfacial Compatibility Enabled by an Ex Situ SEI on Li Anode for LAGP-Based All-Solid-State Batteries.

The electrode-electrolyte interface stability is a critical factor influencing cycle performance of All-solid-state lithium batteries (ASSLBs). Here, we propose a LiF- and Li3N-enriched artificial solid state electrolyte interphase (SEI) protective layer on metallic lithium (Li). The SEI layer can stabilize metallic Li anode and improve the interface compatibility at the Li anode side in ASSLBs. We also developed a Li1.5Al0.5Ge1.5(PO4)3-poly(ethylene oxide) (LAGP-PEO) concrete structured composite solid electrolyte. The symmetric Li/LAGP-PEO/Li cells with SEI-protected Li anodes have been stably cycled with small polarization at a current density of 0.05 mA cm-2 at 50 °C for nearly 400 h. ASSLB-based on SEI-protected Li anode, LAGP-PEO electrolyte, and LiFePO4 (LFP) cathode exhibits excellent cyclic stability with an initial discharge capacity of 147.2 mA h g-1 and a retention of 96% after 200 cycles.

Targeted Delivery of Immunomodulators to Lymph Nodes.

Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node addressin molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo.

Dynamic morphological changes in the skulls of mice mimicking human Apert syndrome resulting from gain-of-function mutation of FGFR2 (P253R).

Apert syndrome is caused mainly by gain-of-function mutations of fibroblast growth factor receptor 2. We have generated a mouse model (Fgfr2(+/P253R)) mimicking human Apert syndrome resulting from fibroblast growth factor receptor 2 Pro253Arg mutation using the knock-in approach. This mouse model in general has the characteristic skull morphology similar to that in humans with Apert syndrome. To characterize the detailed changes of form in the overall skull and its major anatomic structures, euclidean distance matrix analysis was used to quantitatively compare the form and growth difference between the skulls of mutants and their wild-type controls. There were substantial morphological differences between the skulls of mutants and their controls at 4 and 8 weeks of age (P < 0.01). The mutants showed shortened skull dimensions along the rostrocaudal axis, especially in their face. The width of the frontal bone and the distance between the two orbits were broadened mediolaterally. The neurocrania were significantly increased along the dorsoventral axis and slightly increased along the mediolateral axis, and also had anteriorly displayed opisthion along the rostrocaudal axis. Compared with wild-type, the mutant mandible had an anteriorly displaced coronoid process and mandibular condyle along the rostrocaudal axis. We further found that there was catch-up growth in the nasal bone, maxilla, zygomatic bone and some regions of the mandible of the mutant skulls during the 4-8-week interval. The above-mentioned findings further validate the Fgfr2(+/P253R) mouse strain as a good model for human Apert syndrome. The changes in form characterized in this study will help to elucidate the mechanisms through which the Pro253Arg mutation in fibroblast growth factor receptor 2 affects craniofacial development and causes Apert syndrome.

Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses, we found that 2-month-old Fgfr3(G369C/+) mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wild-type mice, Fgfr3(G369C/+) cultures showed decreased cell proliferation, increased osteogenic differentiation including up-regulation of alkaline phosphatase activity and expressions of osteoblast marker genes, and reduced bone matrix mineralization. Furthermore, our studies also suggest that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3(G369C/+) BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization. In addition, in vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3(G369C/+) mice. These findings demonstrate that gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating both osteoblast and osteoclast activities. Our studies provide new insight into the mechanism underlying the development of ACH.