Multibranch Elastic Bound States in the Continuum.

Constructing a highly localized wave field by means of bound states in the continuum (BICs) promotes enhanced wave-matter interaction and offers approaches to high-sensitivity devices. Elastic waves can carry complex polarizations and thus differ from electromagnetic waves and other scalar mechanical waves in the formation of BICs, which is yet to be fully explored and exploited. Here, we report the investigation of local resonance modes supported by a Lamb waveguide side-branched with two pairs of resonant pillars and show the emergence of two groups of elastic BICs with different polarizations or symmetries. Particularly, the two groups of BICs exhibit distinct responses to external perturbations, based on which a label-free sensing scheme with enhanced-sensitivity is proposed. Our study reveals the rich properties of BICs arising from the complex wave dynamics in elastic media and demonstrates their unique functionality for sensing and detection.

Electronic-Structure-Modulated Cu,Co-Coanchored N-Doped Nanocarbon as a Difunctional Electrocatalyst for Hydrogen Evolution and Oxygen Reduction Reactions.

To alleviate the problems of environmental pollution and energy crisis, aggressive development of clean and alternative energy technologies, in particular, water splitting, metal-air batteries, and fuel cells involving two key half reactions comprising hydrogen evolution reaction (HER) and oxygen reduction (ORR), is crucial. In this work, an innovative hybrid comprising heterogeneous Cu/Co bimetallic nanoparticles homogeneously dispersed on a nitrogen-doped carbon layer (Cu/Co/NC) was constructed as a bifunctional electrocatalyst toward HER and ORR via a hydrothermal reaction along with post-solid-phase sintering technique. Thanks to the interfacial coupling and electronic synergism between the Cu and Co bimetallic nanoparticles, the Cu/Co/NC catalyst showed improved catalytic ORR activity with a half-wave potential of 0.865 V and an excellent stability of more than 30 h, even compared to 20 wt% Pt/C. The Cu/Co/NC catalyst also exhibited excellent HER catalytic performance with an overpotential of below 149 mV at 10 mA/cm2 and long-term operation for over 30 h.

Tetrahedral Bonding Structure (Ni3 -Se) Induced by Lattice-Distortion of Ni to Achieve High Catalytic Activity in Na-Se Battery.

Fabrication of transition-metal catalytic materials is regarded as a promising strategy for developing high-performance sodium-selenium (Na-Se) batteries. However, more systematic explorations are further demanded to find out how their bonding interactions and electronic structures can affect the Na storage process. This study finds that lattice-distorted nickel (Ni) structure can form different bonding structures with Na2 Se4 , providing high activity to catalyze the electrochemical reactions in Na-Se batteries. Using this Ni structure to prepare electrode (Se@NiSe2 /Ni/CTs) can realize rapid charge transfer and high cycle stability of the battery. The electrode exhibits high storage performance of Na+ ; i.e., 345 mAh g⁻1 at 1 C after 400 cycles, and 286.4 mAh g⁻1 at 10 C in rate performance test. Further results reveal the existence of a regulated electronic structure with upshifts of the d-band center in the distorted Ni structure. This regulation changes the interaction between Ni and Na2 Se4 to form a Ni3 -Se tetrahedral bonding structure. This bonding structure can provide higher adsorption energy of Ni to Na2 Se4 to facilitate the redox reaction of Na2 Se4 during the electrochemical process. This study can inspire the design of bonding structure with high performance in conversion-reaction-based batteries.

Aberrant BMP15/HIF-1α/SCF signaling pathway in human granulosa cells is involved in the PCOS related abnormal follicular development.

AIMS: To investigate the regulatory mechanism of SCF expression in human GCs of PCOS related follicles. MATERIALS AND METHODS: SCF, BMP15 and HIF-1α were evaluated in human serums, follicular fluids (FFs) and GCs, which were collected from 69 PCOS patients and 74 normal ovulatory patients. KGN cell line was used in this study. RESULTS: Our results showed that the rate of MII oocyte and 2PN fertilization was lower in PCOS group, though PCOS patients retrieved much more oocytes. The level of BMP15 in FF and the level of SCF in serum and FF were also lower in PCOS patients. We found a weakened expression of HIF-1α and SCF in GCs from PCOS patients when compared with the non-PCOS patients. The expression of HIF-1α and SCF was significantly increased in KGN cells after treating cells with rhBMP15, however, this promotion effects of BMP15 on HIF-1α and SCF expression were obviously abolished by co-treatment with BMP-I receptor inhibitor (DM). Moreover, knock down of HIF-1α expression in KGN cells significantly reduced the expression of SCF in human GCs, in spite of activating BMP15 signaling pathway. CONCLUSIONS: The present study suggest that BMP15 could induce SCF expression by up-regulating HIF-1α expression in human GCs, the aberrance of this signaling pathway might be involved in the PCOS related abnormal follicular development.

Simultaneous determination of nirmatrelvir and ritonavir in human plasma using LC-MS/MS and its pharmacokinetic application in healthy Chinese volunteers.

Paxlovid, a copackaged medication of nirmatrelvir tablets (150 mg) and ritonavir tablets (100 mg) developed by Pfizer, is one of the first orally accessible COVID-19 antiviral medicines to be approved for emergency usage. In this research, an efficient LC-MS/MS method for simultaneous determination of nirmatrelvir and ritonavir in human plasma was established and validated with remdesivir as an internal standard. Chromatographic separations were carried out on a Thermo BDS Hypersil C18 column (4.6 × 100 mm, 2.4 µm) using deionized water and methanol as mobile phase, both added with 0.1% (v/v) formic acid. Based on the positive electrospray ionization mode, nirmatrelvir and ritonavir were analyzed by selective reaction monitoring. Excellent precision, accuracy, recovery, and linearity were demonstrated, covering the range of 50-5000 ng/mL for nirmatrelvir and 10-1000 ng/mL for ritonavir. Then, the established method was used for determining the pharmacokinetic profile of Paxlovid in healthy Chinese volunteers. The pharmacokinetic parameters, including Cmax , Tmax , t1/2 , and AUC0 - ∞ of Western volunteers, correspond well with the results of this pharmacokinetic investigation.

A novel heterozygous variant in PANX1 is associated with oocyte death and female infertility.

PURPOSE: Oocyte death is a severe clinical phenotype that causes female infertility and recurrent in vitro fertilization and intracytoplasmic sperm injection failure. We aimed to identify pathogenic variants in a female infertility patient with oocyte death phenotype. METHODS: Sanger sequencing was performed to screen PANX1 variants in the affected patient. Western blot analysis was used to check the effect of the variant on PANX1 glycosylation pattern in vitro. RESULTS: We identified a novel PANX1 variant (NM_015368.4 c.86G > A, (p. Arg29Gln)) associated with the phenotype of oocyte death in a non-consanguineous family. This variant displayed an autosomal dominant inheritance pattern with reduced penetrance. Western blot analysis confirmed that the missense mutation of PANX1 (c.86G > A) altered the glycosylation pattern in HeLa cells. Moreover, the mutation effects on the function of PANX1 were weaker than recently reported variants. CONCLUSION: Our findings expand the inheritance pattern of PANX1 variants to an autosomal dominant mode with reduced penetrance and enrich the variational spectrum of PANX1. These results help us to better understand the genetic basis of female infertility with oocyte death.

Mo-Doped Cu2S Multilayer Nanosheets Grown In Situ on Copper Foam for Efficient Hydrogen Evolution Reaction.

Metal sulfide electrocatalyst is developed as a cost-effective and promising candidate for hydrogen evolution reaction (HER). In this work, we report a novel Mo-doped Cu2S self-supported electrocatalyst grown in situ on three-dimensional copper foam via a facile sulfurization treatment method. Interestingly, Mo-Cu2S nanosheet structure increases the electrochemically active area, and the large fleecy multilayer flower structure assembled by small nanosheet facilitates the flow of electrolyte in and out. More broadly, the introduction of Mo can adjust the electronic structure, significantly increase the volmer step rate, and accelerate the reaction kinetics. As compared to the pure Cu2S self-supported electrocatalyst, the Mo-Cu2S/CF show much better alkaline HER performance with lower overpotential (18 mV at 10 mA cm-2, 322 mV at 100 mA cm-2) and long-term durability. Our work constructs a novel copper based in-situ metal sulfide electrocatalysts and provides a new idea to adjust the morphology and electronic structure by doping for promoting HER performance.

Clinical laboratory characteristics in patients with suspected COVID-19: One single-institution experience.

OBJECTIVES: Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. The aim of the study is to investigate the demographic, clinical, and laboratory characteristics in suspected COVID-19 patients in our institution. METHODS: In this retrospective study, we investigated suspected COVID-19 patients admitted to the University of Alabama at Birmingham with a request for an interleukin-6 send-out test, from March 28 to June 27, 2020. Patients' demographic, clinical, and laboratory characteristics were collected by chart review. RESULTS: Fifty patients suspected with COVID-19 were included in our study, of whom 24 patients were positive with severe acute respiratory syndrome coronavirus-2 infection and 26 were negative. During the observation period, 30 patients were discharged, 17 died during hospitalization, and three remained in hospital. Compared to non-COVID-19 patients, COVID-19 patients had older age, more comorbidities, and elevated levels of inflammation markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and lactate dehydrogenase (LDH). However, there was no significant difference in laboratory data between survivors and nonsurvivors in COVID-19 patients in our study. CONCLUSION: This study indicated that potential risk factors of older age, multiple comorbidities, and high levels of ESR, CRP, serum ferritin, and LDH could help the clinician to identify potential COVID-19 patients. However, this data needs to be further validated in a larger population.

Controlled Synthesis of V-Doped Heterogeneous Ni3S2/NiS Nanorod Arrays as Efficient Hydrogen Evolution Electrocatalysts.

The development of low-cost and high-efficient electrocatalysts toward hydrogen evolution reaction (HER) is highly desirable and challenging. Herein, the novel V-doped Ni3S2/NiS heterostructure nanorod arrays grown on nickel foam (VNS/NF-WM) are synthesized via a facile methanol-assisted hydrothermal method. We demonstrate that the morphology, phase composition, and crystallinity of VNS/NF are well modulated by tuning the ratios of water/methanol solvent. The optimized VNS/NF-WM-heterostructured nanorod (volume ratio of water/methanol is 3:1) exhibits superior HER electrocatalytic activity with low overpotentials of 85 and 218 mV to yield current density values of 10 and 100 mA cm-2, respectively, meanwhile sustaining an excellent stability with almost an unchanged current density of 10 mA cm-2 for 60 h. Our work offers fresh insights into the rational design of highly active and stable earth-abundant-heterostructured electrocatalysts for the hydrogen fuel production.

Biomarkers for monitoring chemotherapy-induced cardiotoxicity.

Cardiotoxicity, including acute and late-onset cardiotoxicity, is a well-known adverse effect of many types of antitumor agents. Early identification of patients with cardiotoxicity is important to ensure prompt treatment and minimize toxic effects. The etiology of chemotherapy-induced cardiotoxicity is multifactorial. Traditional methods for assessment of chemotherapy-induced cardiotoxicity typically involve serial measurements of cardiac function via multi-modality imaging techniques. Typically, however, significant left ventricular dysfunction has already occurred when cardiotoxicity is detected by imaging techniques. Biomarkers, most importantly cardiac natriuretic peptides and troponins, are promising markers for identifying patients potentially at risk for clinical heart failure symptoms. This review summarizes the recent progress in clinical utilization of biomarkers for early diagnosis of acute cardiotoxicity and for prediction of late-onset cardiotoxicity. We also discuss the conflicting results of different studies and the association of results with study design.

Adjusting the Chemical Bonding of SnO2 @CNT Composite for Enhanced Conversion Reaction Kinetics.

Carbon nanotubes (CNTs) with excellent electron conductivity are widely used to improve the electrochemical performance of the SnO2 anode. However, the chemical bonding between SnO2 and CNTs is not clearly elucidated despite it may affect the lithiation/delithiation behavior greatly. In this work, an SnO2 @CNT composite with SnC and SnOC bonds as a linkage bridge is reported and the influence of the SnC and SnOC bonds on the lithium storage properties is revealed. It is found that the SnC bond can act as an ultrafast electron transfer path, facilitating the reversible conversion reaction between Sn and Li2 O to form SnO2 . Therefore, the SnO2 @CNT composite with more SnC bond shows high reversible capacity and nearly half capacity contributes from conversion reaction. It is opposite for the SnO2 @CNT composite with more SnOC bond that the electrons cannot be transferred directly to CNTs, resulting in depressed conversion reaction kinetics. Consequently, this work can provide new insight for exploration and design of metal oxide/carbon composite anode materials in lithium-ion battery.

Utility of chromogranin A, pancreatic polypeptide, glucagon and gastrin in the diagnosis and follow-up of pancreatic neuroendocrine tumours in multiple endocrine neoplasia type 1 patients.

OBJECTIVE: Pancreatic neuroendocrine tumours (PNETs) are the major source of disease-specific mortality in multiple endocrine neoplasia type 1 (MEN1) patients. Chromogranin A (CgA), pancreatic polypeptide (PP), glucagon and gastrin have some diagnostic value in sporadic PNETs, but there is very little evidence for their efficacy in diagnosing PNETs in MEN1 patients. DESIGN: We performed a retrospective chart review of the existing MEN1 database in our institution. PATIENTS: One hundred and thirteen patients were eligible for diagnostic value analysis of tumour markers. Patients were excluded if measurement of tumour markers was missing, either 3 months prior to PNET diagnosis (PNET patients) or prior to abdominal imaging (non-PNET patients). MEASUREMENTS: Clinicopathologic characteristics and of tumour marker measurements were analysed. RESULTS: Of 293 confirmed MEN1 cases, 55 PNETs and 58 non-PNETs met inclusion criteria. The area under the curve (AUC) for CgA, PP, glucagon and gastrin in MEN1 cases was 59·5%, 64·1%, 77·0% and 75·9%, respectively. The AUC for the combination of CgA, PP and gastrin was 59·6%. PP, but not CgA, glucagon or gastrin was significantly associated with both age and PNET functional status (P = 0·0485 and 0·0188, respectively). No markers were significantly associated with sex, PNET size, tumour number, tumour location, American Joint Committee on Cancer (AJCC) stage, presence of lymph node metastasis, lymphovascular invasion or overall survival. CgA values were not significantly lower following PNET resection than pre-operatively (P = 0·554). CONCLUSIONS: The value of blood markers for diagnosing PNETs in MEN1 patients is relatively low, even when used in combination.

Tissue transglutaminase regulates ß-catenin signaling through a c-Src-dependent mechanism.

Tissue transglutaminase (TG2) is a multifunctional enzyme involved in protein cross-linking and cell adhesion to fibronectin (FN). In cancer, TG2 induces an epithelial to mesenchymal transition, contributing to metastasis. Because cadherins bind ß-catenin at cell-cell junctions, disruption of adherens junctions destabilizes cadherin-catenin complexes. The goal of the present study was to analyze whether and how TG2 interacts with and regulates ß-catenin signaling in ovarian cancer (OC) cells. We observed a significant correlation between TG2 and ß-catenin expression levels in OC cells and tumors. TG2 augmented Wnt/ß-catenin signaling, as evidenced by enhanced ß-catenin transcriptional activity, inducing transcription of target genes cyclin D1 and c-Myc. By promoting integrin-mediated cell adhesion to FN, TG2 physically associates with and recruits c-Src, which in turn phosphorylates ß-catenin at Tyr(654), releasing it from E-cadherin and rendering it available for transcriptional regulation. By interacting with FN and enhancing ß-catenin signaling, complexed TG2 stimulates OC cell proliferation. In summary, our data demonstrate that TG2 regulates ß-catenin expression and function in OC cells and define the c-Src-dependent mechanism through which this occurs.

Vapor deposition strategy for implanting isolated Fe sites into papermaking nanofibers-derived N-doped carbon aerogels for liquid Electrolyte-/All-Solid-State Zn-Air batteries.

Single-atom catalysts (SACs), with precisely controlled metal atom distribution and adjustable coordination architecture, have gained intensive concerns as efficient oxygen reduction reaction (ORR) electrocatalysts in Zn-air batteries (ZAB). The attainment of a monodispersed state for metallic atoms anchored on the carbonaceous substrate remains the foremost research priority; however, the persistent challenges lie in the relatively weak metal-support interactions and the instability of captured single atom active sites. Furthermore, in order to achieve rapid transport of O2 and other reactive substances within the carbon matrix, manufacturing SACs based on multi-stage porous carbon substrates is highly anticipated. Here, we propose a methodology for the fabrication of carbon aerogels (CA)-supported SACs utilizing papermaking nanofibers, which incorporates advanced strategies for N-atom self-doping, defect/vacancy introduction, and single-atom interface engineering. Specifically, taking advantages of using green and energy-efficient feedstocks, combining with a direct pore-forming template volatilization and chemical vapor deposition approach, we successfully developed N-doped carbon aerogels immobilized with separated iron sites (Fe-SAC@N/CA-Cd). The obtained Fe-SAC@N/CA-Cd exhibited substantially large specific surface area (SBET = 1173 m2/g) and a multi-level pore structure, which can effectively mitigate the random aggregation of Fe atoms during pyrolysis. As a result, it demonstrated appreciable activity and stability in catalyzing the ORR progress (E1/2 = 0.88 V, Eonset = 0.96 V). Furthermore, the assembled liquid electrolyte-state Zn-air batteries (LES-ZAB) and all-solid-state Zn-air battery (ASS-ZAB) also provides encouraging performance, with a peak power density of 169 mW cm-2 for LES-ZAB and a maximum power density of 124 mW cm-2 for ASS-ZAB.

Reduced PATL2 Impairs the Proliferation of Ovarian Granulosa Cells by Decreasing ADM2 Expression in Patients with PCOS.

It is recognized that PCOS patients are often accompanied with aberrant follicular development, which is an important factor leading to infertility in patients. However, the relevant regulatory mechanisms of abnormal follicular development are not well understood. In the present study, by collecting human ovarian granulosa cells (GCs) from PCOS patients who underwent in vitro fertilization (IVF), we found that the proliferation ability of GCs in PCOS patients was significantly reduced. Surprisingly, PATL2 and adrenomedullin 2 (ADM2) were obviously decreased in the GCs of PCOS patients. To further explore the potential roles of PATL2 and ADM2 on GC, we transfected PATL2 siRNA into KGN cells to knock down the expression of PATL2. The results showed that the growth of GCs remarkably repressed after knocking down the PATL2, and ADM2 expression was also weakened. Subsequently, to study the relationship between PATL2 and ADM2, we constructed PATL2 mutant plasmid lacking the PAT construct and transfected it into KGN cells. The cells showed the normal PATL2 expression, but attenuated ADM2 expression and impaired proliferative ability of GCs. Finally, the rat PCOS model experiments further confirmed our findings in KGN cells. In conclusion, our study suggests that PATL2 promoted the proliferation of ovarian GCs by stabilizing the expression of ADM2 through "PAT" structure, which is beneficial to follicular development, whereas, in the ovary with polycystic lesions, reduction of PATL2 could result in the decreased expression of ADM2, subsequently weakened the proliferation ability of GCs and finally led to the occurrence of aberrant follicles.

Observation of phononic skyrmions based on hybrid spin of elastic waves.

Skyrmions with topologically stable configuration have shown a promising route toward high-density magnetic and photonic information processing due to their defect-immune and low-driven energy. Here, we experimentally report and observe the existence of phononic skyrmions as new topological structures formed by the three-dimensional hybrid spin of elastic waves. We demonstrate that the frequency-independent spin configuration leads to ultra-broadband feature of phononic skyrmions, which can be produced in any solid structure, including chip-scale ones. We further experimentally show the excellent robustness of the flexibly movable phononic skyrmion lattices against local defects of disorder, sharp corners, and even rectangular holes. Our research opens a vibrant horizon toward an unprecedented way for elastic wave manipulation and structuration by spin configuration and offers a promising lever for alternative phononic technologies, including information processing, biomedical testing, and wave engineering.

The anti-myotoxic effects and mechanisms of Sinonatrix annularis serum and a novel plasma metalloproteinase inhibitor towards Deinagkistrodon acutus envenomation.

Non-venomous snakes commonly evolve natural resistance to venom to escape predators. Sinonatrix annularis serum has been shown to inhibit Deinagkistrodon acutus venom-induced hemorrhage and upregulation of serum CK, CK-MB, LDH, AST and ALT levels. Using TMT-labeled proteomics analysis, 168 proteins were found to be altered significantly in the envenomed gastrocnemius muscle and categorized into pathways such as complement and coagulation cascades, leukocyte transendothelial migration, and JAK/STAT signaling. These alterations were mitigated by S. annularis serum. Subsequently, a novel metalloproteinase inhibitor, SaMPI, was isolated from S. annularis serum by two-step chromatography. It showed strong antidotal effects against D. acutus envenomation, including inhibition of subcutaneous bleeding caused by crude venom and DaMP (a metalloproteinase derived from D. acutus) activity in a 1:1 ratio. Histology and immunoblotting analyses demonstrated that SaMPI mitigated myonecrosis, reduced neutrophil infiltration and local inflammatory factor release, and retarded JAK/STAT and MAPK signaling activation. Analysis of the SaMPI gene cloned by 5'-RACE revealed a shared sequence identity of 58-79% with other SVMP inhibitors. These findings demonstrate the protective effects of SaMPI and indicate its potential value as a candidate for viper bite adjuvant therapy.

High-density low-coordination Ni single atoms anchored on Ni-embedded nanoporous carbon nanotubes for boosted alkaline hydrogen evolution.

Modulating the coordination environment of single-atom catalysts is considered an effective way to boost the electrocatalytic activity of the hydrogen evolution reaction. Herein, a novel electrocatalyst comprising high-density low-coordination Ni single atoms anchored on Ni-embedded nanoporous carbon nanotubes (Ni-N-C/Ni@CNT-H) is constructed through a self-template assisted synthetic strategy. We demonstrate that the in situ generated AlN nanoparticles not only serve as the template for the formation of the nanoporous structure, but also contribute to the coordination between Ni and N atoms. Benefiting from the optimized charge distribution and hydrogen adsorption free energy of the unsaturated Ni-N2 active structure and nanoporous structure of the carbon nanotube substrate, the resultant Ni-N-C/Ni@CNT-H exhibited outstanding electrocatalytic hydrogen evolution activity with a low overpotential of 175 mV at a current density of 10 mA cm-2, and a long-term durability for over 160 h in continuous operation. This work provides a new insight and approach to the design and synthesis of efficient single-atom electrocatalysts toward hydrogen fuel production.

V-doped Ni2P nanoparticle grafted g-C3N4 nanosheets for enhanced photocatalytic hydrogen evolution performance under visible light.

Exploring low-cost and highly active photocatalysts with noble metal-free cocatalysts is of great significance for photocatalytic hydrogen evolution under simulated sunlight irradiation. In this work, a novel V-doped Ni2P nanoparticle loaded g-C3N4 nanosheet is reported as a highly efficient photocatalyst for H2 evolution under visible light irradiation. The results demonstrate that the optimized 7.8 wt% V-Ni2P/g-C3N4 photocatalyst exhibits a high hydrogen evolution rate of 271.5 µmol g-1 h-1, which is comparable to that of the 1 wt% Pt/g-C3N4 photocatalyst (279 µmol g-1 h-1), and shows favorable hydrogen evolution stability for five successive runs within 20 h. The remarkable photocatalytic hydrogen evolution performance of V-Ni2P/g-C3N4 is mainly due to the enhanced visible light absorption ability, the facilitated separation of photo-generated electron-hole pairs, the prolonged lifetime of photo-generated carriers and the fast transmission ability of electrons.