MOF-derived porous carbon nanozyme-based flexible electrochemical sensing system for in situ and real-time monitoring of H2O2 released from cells.

A novel flexible electrochemical sensor based on porous carbon nanosheets (PCNSs) nanozyme has been constructed for in situ and real-time monitoring of H2O2 released by cells. The PCNSs are prepared with the integration of thermal transformation, thermal activation and sonochemical exfoliation by using zeolitic imidazolate frameworks as template. The PCNSs exhibit high electrical conductivity, electrochemical activity and peroxidase-like catalytic properties, which is beneficial to H2O2 assay. With the transfer printing method, the flexible electrochemical sensor is obtained, which has excellent performances for H2O2 electrochemical detecting with wide linear range from 1 µM to 20 mM and a low detection limit of 0.76 µM. Owing to the great biocompatibility, the flexible sensor guarantees the growth of living cells for 72 h and realizes in situ and real-time monitoring the release of H2O2 from HeLa cells. The strategy of porous nanozyme preparation and flexible sensor construction provided a promising way for in situ and real-time assay of small molecules in the cellular microenvironment.

YangXueQingNaoWan attenuated blood brain barrier disruption after thrombolysis with tissue plasminogen activator in ischemia stroke.

ETHNOPHARMACOLOGICAL RELEVANT: YangXueQingNaoWan (YXQNW), a compound Chinese medicine, has been widely used for dizziness, irritability, insomnia, and dreaminess caused by blood deficiency and liver hyperactivity in China. However, whether YXQNW can inhibit cerebral microvascular exudation and cerebral hemorrhage (CH) caused by blood brain barrier (BBB) damage after tissue plasminogen activator (tPA) still unknown. AIM OF THE RESEARCH: To observe the effect of YXQNW on cerebral microvascular exudation and CH after tPA and investigate its mechanism in protecting BBB. MATERIALS AND METHODS: Male C57BL/6 N mice suffered from ischemia stroke by mechanical detachment of carotid artery thrombi with the stimulation of ferric chloride. Then mice were treated with tPA (10 mg/kg) and/or YXQNW (0.72 g/kg) at 4.5 h. Cerebral blood flow (CBF), infarct size, survival rate, neurological scores, gait analysis, Evans blue extravasation, cerebral water content, fluorescein isothiocyanate-labeled albumin leakage, hemorrhage, junction and basement membrane proteins expression, leukocyte adhesion and matrix metalloproteinases (MMPs) expression were evaluated 24 h after tPA. Proteomics was used to identify target proteins. RESULTS: YXQNW inhibited cerebral infarction, neurobehavioral deficits, decreased survival, Evans blue leakage, albumin leakage, cerebral water content and CH after tPA thrombolysis; improved CBF, low-expression and degradation of junction proteins, basement membrane proteins, Arhgap21 and its downstream α-catenin and ß-catenin proteins expression; and suppressed the increase of adherent leukocytes and the release of MMP-9 derived from macrophage. CONCLUSION: YXQNW relieved BBB damage and attenuated cerebral microvascular exudation and CH after tPA thrombolysis. The effect of YXQNW on cerebral microvascular exudation was associated with the inhibition of the low-expression of junction proteins, especially AJs mediated by Rho GTPase-activating protein 21 (Arhgap21), while the effect on CH was associated with the inhibition of leukocyte adhesion, the release of MMP-9 derived from macrophage, and low-expression and degradation of collagen IV and laminin in the vascular basement membrane.

Baitouweng decoction repairs the intestinal barrier in DSS-induced colitis mice via regulation of AMPK/mTOR-mediated autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is one of non-specific inflammatory bowel disease that mainly affects the colon. Recently, UC has become a significant social and economic problem worldwide. Baitouweng decoction (BD), a traditional Chinese medicine described in the "Treatise on Febrile Diseases", has been used for centuries to treat intestinal diseases. However, its underlying mechanism remains largely unexplored. AIM OF STUDY: In this study, we aimed to investigate the effect of BD on autophagy for repairing the colonic barrier in DSS-induced colitis mice and explored its role in regulating the autophagic signaling pathway AMPK/mTOR. MATERIALS AND METHODS: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 7 days. The effectiveness of BD in treating DSS-induced colitis was evaluated through body weight, disease activity index (DAI), colon length, pathological changes, organ index, and proportion of blood cells. Moreover, intestinal epithelial permeability was analyzed by examining FITC-dextran leakage, the bacterial load of mesenteric lymph nodes (MLNs), and bacterial infiltration of colon tissues. Barrier function was evaluated by assessing the number and proportion of colonic goblet cells and the expression of tight junction proteins, including ZO-1, claudin-1, and occludin. Furthermore, the levels of autophagy were assessed by examining the number of autophagosomes and the expression of the autophagy-related proteins LC3, Beclin1, and P62. Additionally, network pharmacology research was conducted to analyze the potential mechanisms underlying the medicinal effects, as indicated by the role of AMPK/mTOR in regulating the autophagic signaling pathway. RESULTS: BD improved colitis symptoms in mice by restoring body weight and colon length and reducing inflammatory cell infiltration. Additionally, BD decreased the diffusion of FITC-dextran and bacterial translocation in MLNs, as well as bacterial infiltration of the colonic mucosa. The number and proportion of colonic goblet cells, the expression of ZO-1, Claudin-1, and Occludin, and the levels of autophagy were also increased by BD. Network pharmacology analysis suggested that BD might affect intestinal autophagy through the AMPK signaling pathway, which was confirmed by the activation of AMPK phosphorylation and the downregulation of mTOR expression following BD treatment. CONCLUSION: Our study demonstrated that BD repaired the intestinal epithelial barrier in DSS-induced colitis mice by activating AMPK phosphorylation and inhibiting mTOR expression to promote autophagy.

Evaluation of the efficacy and safety of Suxiao Jiuxin Pill in the treatment of stable angina: A randomized, double-blind, placebo-controlled, multi-center clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The Suxiao Jiuxin Pill (SJP) has been used for treating chronic stable angina (SA) for more than 40 years in China. SJP is composed of two Chinese herbs and has the effect of activating blood and promoting qi, according to traditional Chinese medicine (TCM) theory. AIM OF THE STUDY: The study aims to determine the effects of adjunct SJP on conventional therapy in patients with SA which provides a complementary choice and its evidence for clinical medication for treating SA. MATERIALS AND METHODS: Participants with SA were recruited and randomized 1:1 to either the SJP group or the control group for 24 weeks. Both groups received conventional treatment according to local tertiary hospital protocols, and the participants received additional SJP (composed of Ligusticum wallichii and Borneol) or placebo in treatment and control groups respectively. The primary outcome was the curative efficacy rate at week 4. Secondary outcomes are the curative efficacy rate, the total score of angina pectoris symptoms, CCS Angina Classification improvement, Seattle Angina Questionnaire (SAQ) score, TCM syndrome scores (TCMSS), and the curative efficacy rate of TCMSS. Adverse events and adverse drug reactions were observed and recorded for safety analysis. RESULTS: A total of 324 participants with SA from 13 hospitals in China were enrolled in this trial. Compared with the control group, the curative efficacy rate of SA, the curative efficacy rate of TCMSS significantly increased, and the total score of angina pectoris symptoms and TCMSS significantly reduced in the SJP group at week 4, 12, and 24, accompanied by the statistically significant improvement in the curative efficacy rate based on CCS grade reduction (all P < 0.05). Furthermore, the SAQ score (physical limitation, angina stability, and treatment satisfaction) was evaluated as the quality of life significantly improved after treatment (P < 0.05). The medication compliance, concomitant medication, and rates of adverse events were similar between the two groups (P > 0.05). CONCLUSION: The present prospective, multicenter, randomized, double-blind, placebo-controlled, clinical trial confirms that adjunct SJP to conventional treatment increased the curative efficacy and life quality of SA patients with no significant adverse drug reactions during the clinical application. CLINICAL TRIAL REGISTRATION: (ID, ChiCTR1900021876, URL = http://www.chictr.org.cn/showproj.aspx?proj=34955).

Improvement and Evaluation of a Device That Determines the Interfacial Shear Strength of Carbon Fiber/Polyphenylene Sulfide Composites.

This study improved homemade apparatus for characterizing the interfacial shear strength (IFSS) of carbon-fiber-reinforced polyphenylene sulfide (PPS/CF) composites. The upgraded generation II experimental device includes a newly developed experimental clamp for samples, as well as testing systems. Compared with the initial generation I apparatus and the commercial Toei instrument, the generation II device is easier and more efficient to operate. The average interfacial adhesion values obtained using these devices were consistently approximately 40 MPa, with relatively low data scatter, showing excellent repeatability and applicability during microbond tests. Notably, the generation II experimental device was equipped with an additional high-frequency data-capturing tool to identify the debonding peak force more precisely, which demonstrated a higher interfacial shear strength of 42.81 MPa during testing. Therefore, the new instrument was able to reflect the change in the interfacial stress state during the interface debonding process more accurately and reliably.

Effects of Electron Irradiation and Temperature on Mechanical Properties of Polyimide Film.

Polyimide (PI) is widely deployed in space missions due to its good radiation resistance and durability. The influences from radiation and harsh temperatures should be carefully evaluated during the long-term service life. In the current work, the coupled thermal and radiation effects on the mechanical properties of PI samples were quantitatively investigated via experiments. At first, various PI specimens were prepared, and electron irradiation tests were conducted with different fluences. Then, both uniaxial tensile tests at room temperature and the dynamic mechanical analysis at varied temperatures of PI specimens with and without electron irradiation were performed. After that, uniaxial tensile tests at low and high temperatures were performed. The fracture surface of the PI film was observed using a scanning electron microscope, and its surface topography was measured using atomic force microscopy. In the meantime, the Fourier-transform infrared spectrum tests were conducted to check for chemical changes. In conclusion, the tensile tests showed that electron irradiation has a negligible effect during the linear stretching period but significantly impacts the hardening stage and elongation at break. Moreover, electron irradiation slightly influences the thermal properties of PI according to the differential scanning calorimetry results. However, both high and low temperatures dramatically affect the elastic modulus and elongation at break of PI.

Defunctioning stoma and anastomotic stricture in rectal cancer surgery: a propensity score matching study.

BACKGROUND: In cases of rectal cancer surgery, patients at high risk of anastomotic leakage often receive a defunctioning stoma (DS). However, its role in postoperative anastomotic strictures (AS) remains unclear. This study aimed to investigate the correlation between DS and AS and outcomes of transanal endoscopic microsurgery (TEM) in treating rectal AS. METHODS: This retrospective study was conducted from January 2019 to September 2021 and included patients who underwent rectal cancer surgery. A 1:1 ratio was used for propensity score matching (PSM). Univariate analyses were performed to identify statistically significant variables, and multivariate analyses were conducted to determine the factors affecting AS. RESULTS: This study included 383 patients. The results of the univariate analysis suggested that surgery time (HR 4.597, 95% CI 1.563-13.525, P=0.006), postoperative anastomotic leakage (HR 11.830, 95% CI 3.773-37.094, P<0.001), and DS (HR 15.475, 95% CI 6.042-39.641, P<0.001) were significantly associated with AS. In the multivariate analysis, postoperative anastomotic leakage (HR 7.596, 95% CI 1.987-29.044, P= 0.003) and DS (HR 11.252, 95% CI 4.113-30.779, P<0.001) were identified as significant risk factors for AS. After matching, the univariate analysis revealed that postoperative anastomotic leakage (HR 8.333, 95% CI 1.541-45.052, P= 0.014) and DS (HR 9.965, 95% CI 2.200-45.142, P= 0.003) were associated with AS. The multivariate analysis indicated that postoperative anastomotic leakage (HR 14.549, 95% CI 1.765-119.913, P= 0.013) and DS (HR 12.450, 95% CI 2.418-64.108, P= 0.003) were significant risk factors for AS. CONCLUSIONS: This study provides evidence that DS is independently associated with AS, and postoperative anastomotic leakage increases the risk of AS. Furthermore, this study suggests that TEM could be a valuable treatment option for AS.

The impact of the national volume-based procurement policy on the use of policy-related drugs in Nanjing: an interrupted time-series analysis.

BACKGROUND: In September 2019, the "4 + 7" centralized procurement pilot program was expanded nationwide aiming at reducing drug prices by means of volume-based procurement and using accredited generic drugs for branded drug substitutes. Given the current uncertain effect of the policy outside pilot areas, this study was conducted to evaluate the impact of the National Volume-based Procurement policy on the use of policy-related drugs after expansion. METHOD: A single-group interrupted time series was applied using drug purchase data, covering 25 months from December 2018 to December 2020. Drugs related to the centralized procurement policy were selected as samples, including 25 first-batch policy-related drugs and 56 alternative drugs. Centralized procured drugs can be divided into bid-winning and non-winning products, where non-winning products were sorted into generic and branded drugs, and alternative products were classified according to different degrees of substitution. Purchase volume, expenditures, and daily costs were measured. RESULTS: After the implementation of the policy, a significant increase was associated with the volume of bid-winning drugs (p < 0.001) and the volume of generic and branded drugs decreased immediately. The DDDc of drugs under the same generic name significantly reduced (an instantaneous drop of bid-winning drugs by approximately 25%, 7.62 CNY for generics and 3.07 CNY for branded drugs), saving 48.2 million CNY of drug expenditures. The policy has a significant effect on the drug for the treatment of cardiovascular diseases and exerted little influence on the drug for the treatment of nervous diseases, and the substitution of generics for antitumor-branded drugs was not obvious. In addition, the procurement volume of alternative drugs appeared to be a "carry-over". CONCLUSIONS: These findings indicated that the policy demonstrated positive effects in terms of price reductions and cost savings and accelerated the substitution of generics against branded drugs. The "patent cliff" for branded drugs has gradually emerged. Besides, a short-term "spillover effect" of the volume of alternative drugs was observed, requiring special attention and vigilance.

circ_0000018 downregulation peripherally ameliorates neuroprotection against acute ischemic stroke through the miR­871/BCL2L11 axis.

Acute ischemic stroke (AIS) is a common acute cerebrovascular disease. Circular RNAs (circRNAs) have been demonstrated to have critical functions in a wide range of physiological processes and disorders in humans. However, their precise function in ischemic stroke (IS) remains largely unknown. The present study explored the function and potential mechanisms of circ_0000018 in AIS in vivo and in vitro. The cerebral ischemia/reperfusion injury model was established in vivo and in vitro using the oxygen­glucose deprivation (OGD/R) and transient middle cerebral artery occlusion (tMCAO) methods. Subsequently, the impact of circ_0000018 on cerebral ischemia/reperfusion injury was assessed using various techniques, including TTC staining, quantitative PCR, western blotting, cell counting kit­8 assay, Annexin V­FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others. The levels of circ_0000018 were markedly increased in the OGD/R­treated neuronal cells and in a mouse model of tMCAO. The blocking of microRNA (miR)­871 by circ_0000018 promoted Bcl­2­like protein 11 (BCL2L11) expression to increase neuronal cell damage. Furthermore, circ_0000018 knockdown significantly improved neuronal cell viability and attenuated OGD/R­treated neuronal cell death. Meanwhile, circ_0000018 knockdown improved brain infarct volume and neuronal apoptosis in tMCAO mice. The present study found that circ_0000018 knockdown relieved cerebral ischemia­reperfusion injury progression in vitro and in vivo. Mechanistically, circ_0000018 regulated the levels of BCL2L11 by sponging miR­871.

Mitochondrial VOLTAGE-DEPENDENT ANION CHANNEL 3 regulates stomatal closure by abscisic acid signaling.

In Arabidopsis (Arabidopsis thaliana), stomatal closure mediated by abscisic acid (ABA) is redundantly controlled by ABA receptor family proteins (PYRABACTIN RESISTANCE 1 (PYR1)/PYR1-LIKE [PYLs]) and subclass III SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2 (SnRK2s). Among these proteins, the roles of PYR1, PYL2, and SnRK2.6 are more dominant. A recent discovery showed that ABA-induced accumulation of reactive oxygen species (ROS) in mitochondria promotes stomatal closure. By analyzing stomatal movements in an array of single and higher order mutants, we revealed that the mitochondrial protein VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3) jointly regulates ABA-mediated stomatal closure with a specialized set of PYLs and SnRK2s by affecting cellular and mitochondrial ROS accumulation. VDAC3 interacted with nine PYLs and all three subclass III SnRK2s. Single mutation in VDAC3, PYLs (except PYR1 and PYL2), or SnRK2.2/2.3 had little effect on ABA-mediated stomatal closure. However, knocking out PYR1, PYL1/2/4/8, or SnRK2.2/2.3 in vdac3 mutants resulted in significantly delayed or attenuated ABA-mediated stomatal closure, despite the presence of other PYLs or SnRK2s conferring redundant functions. We found that cellular and mitochondrial accumulation of ROS induced by ABA was altered in vdac3pyl1 mutants. Moreover, H2O2 treatment restored ABA-induced stomatal closure in mutants with decreased stomatal sensitivity to ABA. Our work reveals that VDAC3 ensures redundant control of ABA-mediated stomatal closure by canonical ABA signaling components.

Determining the Number of Graphene Nanoribbons in Dual-Gate Field-Effect Transistors.

Bottom-up synthesized graphene nanoribbons (GNRs) are increasingly attracting interest due to their atomically controlled structure and customizable physical properties. In recent years, a range of GNR-based field-effect transistors (FETs) has been fabricated, with several demonstrating quantum-dot (QD) behavior at cryogenic temperatures. However, understanding the relationship between the cryogenic charge-transport characteristics and the number of the GNRs in the device is challenging, as the length and location of the GNRs in the junction are not precisely controlled. Here, we present a methodology based on a dual-gate FET that allows us to identify different scenarios, such as single GNRs, double or multiple GNRs in parallel, and a single GNR interacting with charge traps. Our dual-gate FET architecture therefore offers a quantitative approach for comprehending charge transport in atomically precise GNRs.

Magnetic Topological Insulator MnBi2Te4 Nanosheets for Femtosecond Pulse Generation.

The van der Waals layered material MnBi2Te4, as a magnetic topological insulator, has attracted tremendous interest for novel physics research in the fields of condensed matter physics and materials science. However, the nonlinear optical properties of MnBi2Te4 and its applications in ultrafast optics have rarely been explored. In this study, high-quality MnBi2Te4 nanosheets have been successfully synthesized by the self-flux method. The morphology, chemical composition, magnetic properties, and nonlinear optical characteristics were systematically investigated. The magnetic transition of MnBi2Te4 was confirmed by a low-temperature spatially resolved spectroscopic technique. The saturable absorption property of MnBi2Te4 was measured by a balanced twin-detector system with a modulation depth of 4.5% and a saturation optical intensity of 2.35 GW/cm2. Furthermore, by inserting the MnBi2Te4-based saturable absorber, a soliton mode-locking laser operating at 1558.8 nm was obtained with a pulse duration of 331 fs. This research will pave the way for applications of the magnetic TI MnBi2Te4 in nonlinear optics and photonics.

Intrinsic Stress-strain in Barium Titanate Piezocatalysts Enabling Lithium-Oxygen Batteries with Low Overpotential and Long Life.

Rechargeable lithium-oxygen (Li-O2 ) batteries with high theoretical energy density are considered as promising candidates for portable electronic devices and electric vehicles, whereas their commercial application is hindered due to poor cyclic stability caused by the sluggish kinetics and cathode passivation. Herein, the intrinsic stress originated from the growth and decomposition of the discharge product (lithium peroxide, Li2 O2 ) is employed as a microscopic pressure resource to induce the built-in electric field, further improving the reaction kinetics and interfacial Lithium ion (Li+ ) transport during cycling. Piezopotential caused by the intrinsic stress-strain of solid Li2 O2 is capable of providing the driving force for the separation and transport of carriers, enhancing the Li+ transfer, and thus improving the redox reaction kinetics of Li-O2 batteries. Combined with a variety of in situ characterizations, the catalytic mechanism of barium titanate (BTO), a typical piezoelectric material, was systematically investigated, and the effect of stress-strain transformation on the electrochemical reaction kinetics and Li+ interface transport for the Li-O2 batteries is clearly established. The findings provide deep insight into the surface coupling strategy between intrinsic stress and electric fields to regulate the electrochemical reaction kinetics behavior and enhance the interfacial Li+ transport for battery system.

Recent progress of molybdenum carbide based electrocatalysts for electrocatalytic hydrogen evolution reaction.

Electrocatalytic hydrogen evolution reaction (HER) is one of the most promising and clean strategies to prepare hydrogen on a large scale. Nevertheless, the efficiency of HER is greatly restricted by the large overpotential at the anode, and it is necessary to develop low cost electrocatalysts with excellent performance and stability. Molybdenum carbide has shown great potential in the field of HER due to its unique electronic structure and physical and chemical properties. In this paper, the current progress of molybdenum carbide-based catalysts for HER is summarized. The influence of phase structure, nanostructure, heterostructure and heteroatoms doping on its catalytic performance is discussed in detail. Especially, the catalytic mechanisms are analyzed according to structural characterization and theoretical calculation results. Finally, the challenges and prospects for the further development of molybdenum carbide-based catalysts for HER are put forward to guide the progress of this field.

C3N nanodots inhibits Aß peptides aggregation pathogenic path in Alzheimer's disease.

Despite the accumulating evidence linking the development of Alzheimer's disease (AD) to the aggregation of Aß peptides and the emergence of Aß oligomers, the FDA has approved very few anti-aggregation-based therapies over the past several decades. Here, we report the discovery of an Aß peptide aggregation inhibitor: an ultra-small nanodot called C3N. C3N nanodots alleviate aggregation-induced neuron cytotoxicity, rescue neuronal death, and prevent neurite damage in vitro. Importantly, they reduce the global cerebral Aß peptides levels, particularly in fibrillar amyloid plaques, and restore synaptic loss in AD mice. Consequently, these C3N nanodots significantly ameliorate behavioral deficits of APP/PS1 double transgenic male AD mice. Moreover, analysis of critical tissues (e.g., heart, liver, spleen, lung, and kidney) display no obvious pathological damage, suggesting C3N nanodots are biologically safe. Finally, molecular dynamics simulations also reveal the inhibitory mechanisms of C3N nanodots in Aß peptides aggregation and its potential application against AD.

Recent advances in CRISPR-Cas system for the treatment of genetic hearing loss.

Genetic hearing loss has emerged as a significant public health concern that demands attention. Among the various treatment strategies, gene therapy based on gene editing technology is considered the most promising approach for addressing genetic hearing loss by repairing or eliminating mutated genes. The advent of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has revolutionized gene therapy through its remarkable gene editing capabilities. This system has been extensively employed in mammalian gene editing and is currently being evaluated through clinical trials. Against this backdrop, this review aims to provide an overview of recent advances in utilizing the CRISPR-Cas system to treat genetic hearing loss. Additionally, we delve into the primary challenges and prospects associated with the current application of this system in addressing genetic hearing loss.

Efficacy of online cognitive behavioral therapy for nonorganic erectile dysfunction in reproductive-age males during the COVID-19 pandemic: a randomized wait list-controlled trial.

BACKGROUND: Previous research has documented the impact of the COVID-19 pandemic on male sexual and mental health. However, no prior study has evaluated the efficacy of online cognitive behavioral therapy (CBT) during the COVID-19 pandemic for treating nonorganic erectile dysfunction (ED) by improving negative emotions and self-esteem. AIM: To test the efficacy of online CBT for nonorganic ED during the COVID-19 pandemic in Shanghai, China. METHODS: A randomized controlled trial was conducted during the COVID-19 pandemic. Paired t-tests and 1-way analysis of variance were used to analyze and compare erectile functioning, self-esteem, and emotional state between and within groups. OUTCOMES: The main outcome measures included scores on the 5-item International Index of Erectile Function, Rosenberg Self-esteem Scale, 9-item Patient Health Questionnaire, and 7-item Generalized Anxiety Disorder scale to evaluate erectile functioning, self-esteem, depression, and anxiety, respectively. RESULTS: In the CBT group, erectile functioning, intercourse satisfaction, orgasmic functioning, sexual desire, and overall satisfaction were significantly improved at posttreatment as compared with pretreatment (P < .05). After treatment, group differences in emotional state and self-esteem were observed between the CBT group and the control group. Results revealed that the CBT group had significantly better scores than the control group at posttreatment on the Rosenberg Self-esteem Scale (mean ± SD, 30.43 ± 6.51 vs 22.67 ± 10.74), Patient Health Questionnaire (7.07 ± 2.74 vs 11.07 ± 4.41), and Generalized Anxiety Disorder scale (8.36 ± 1.97 vs 11.13 ± 3.94; P < .05). CLINICAL IMPLICATIONS: This study represents an important advance in understanding of the efficacy of online CBT for treating nonorganic ED in reproductive-age males during the COVID-19 pandemic. STRENGTHS AND LIMITATIONS: The study participants, treatment modality, and COVID-19 pandemic background of this study are innovative and therefore strengths. However, our study has several limitations-namely, its sample size and use of self-report data to measure erectile functioning due to the pandemic. Further studies should incorporate sexual functioning-monitoring instruments as well as self-report data to measure erectile function. CONCLUSION: Online CBT clearly improved the emotional state and self-esteem of patients with ED during the COVID-19 pandemic.

Highly stable lanthanide(III) metal-organic frameworks as ratiometric fluorescence sensors for vitamin B6.

Three lanthanide(III)-based metal-organic frameworks, formulated as [(CH3)2NH2]2[Ln6(µ3-OH)8(EBTC)3(H2O)6]·4H2O·2DMF (Ln = Eu (1), Tb (2) and Ce (3)), were synthesized using a rigid tetracarboxylate organic ligand (1,1'-ethynebenzene-3,3',5,5'-tetracarboxylic acid, H4EBTC). Complexes 1-3 possess 12-connected hexanuclear [Ln6(µ3-OH)8(OOC-)12(H2O)6] clusters with the ftw topology, which were stable in water and acid/alkaline aqueous solution. Due to the antenna effect, complexes 1 and 2 presented double fluorescence emission peaks, which are the characteristic emission peaks of Ln3+ ions and the ligand H4EBTC, respectively. The doped bimetallic EuxTb1--x-MOFs were obtained by tuning the Eu(III)/Tb(III) ratio during the reaction, which exhibited a colour change from red, orange, and yellow to green. Furthermore, complexes 1, 2 and Eu2Tb8-MOF as ratiometric fluorescence sensors exhibited excellent sensing ability for vitamin B6 (VB6) in phosphate buffer solution (pH = 7.35) and real samples with high selectivity and reusability. The low detection limit (LOD) values were calculated to be 1.03 µM for complex 1, 0.25 µM for complex 2 and 0.11 µM for Eu2Tb8-MOF in aqueous solution. Finally, a visual film based on Ln-MOF@SA was prepared to detect VB6 with high reusability.

Polymorphonuclear myeloid-derived suppressor cells and phosphatidylinositol-3 kinase gamma are critical to tobacco-mimicking oral carcinogenesis in mice.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC. METHODS: Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation. RESULTS: In our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner. CONCLUSIONS: Overall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC.

MXene-Derived Na+ -Pillared Vanadate Cathodes for Dendrite-Free Potassium Metal Batteries.

Cation-intercalated vanadates, which have considerable promise as the cathode for high-performance potassium metal batteries (PMBs), suffer from structural collapse upon K+ insertion and desertion. Exotic cations in the vanadate cathode may ease the collapse, yet their effect on the intrinsic cation remains speculative. Herein, a stable and dendrite-free PMB, composed of a Na+ and K+ co-intercalated vanadate (NKVO) cathode and a liquid NaK alloy anode, is presented. A series of NKVO with tuneable Na/K ratios are facilely prepared using MXene precursors, in which Na+ is testified to be immobilized upon cycling, functioning as a structural pillar. Due to stronger ionic bonding and lower Fermi level of Na+ compared to K+ , moderate Na+ intercalation could reduce K+ binding to the solvation sheath and favor K+ diffusion kinetics. As a result, the MXene-derived Na+ -pillared NKVO exhibits markedly improved specific capacities, rate performance, and cycle stability than the Na+ -free counterpart. Moreover, thermally-treated carbon paper, which imitates the microscopic structure of Chinese Xuan paper, allows high surface tension liquid NaK alloy to adhere readily, enabling dendrite-free metal anodes. By clarifying the role of foreign intercalating cations, this study may lead to a more rational design of stable and high-performance electrode materials.