Vapor Phase Growth of Air-Stable Hybrid Perovskite FAPbBr3 Single-Crystalline Nanosheets.

Organic-inorganic hybrid perovskites have attracted tremendous attention owing to their fascinating optoelectronic properties. However, their poor air stability seriously hinders practical applications, which becomes more serious with thickness down to the nanoscale. Here we report a one-step vapor phase growth of HC(NH2)2PbBr3 (FAPbBr3) single-crystalline nanosheets of tunable size up to 50 µm and thickness down to 20 nm. The FAPbBr3 nanosheets demonstrate high stability for over months of exposure to air with no degradation in surface roughness and photoluminescence efficiency. Besides, the FAPbBr3 photodetectors exhibit superior overall performance as compared to previous devices based on nonlayered perovskite nanosheets, such as an ultralow dark current of 24 pA, an ultrahigh responsivity of 1033 A/W, an external quantum efficiency over 3000%, a rapid response time around 25 ms, and a high on/off ratio of 104. This work provides a strategy to tackle the challenges of hybrid perovskites toward integrated optoelectronics with requirements of nanoscale thickness, high stability, and excellent performance.

Charge Generation Dynamics in Organic Photovoltaic Blends under One-Sun-Equivalent Illumination Detected by Highly Sensitive Terahertz Spectroscopy.

Organic photovoltaic (OPV) devices attain high performance with nonfullerene acceptors by utilizing the synergistic dual channels of charge generation that originate from excitations in both the donor and acceptor materials. However, the specific intermediate states that facilitate both channels are subject to debate. To address this issue, we employ time-resolved terahertz spectroscopy with improved sensitivity (ΔE/E < 10-6), enabling direct probing of charge generation dynamics in a prototypical PM6:Y6 bulk heterojunction system under one-sun-equivalent excitation density. Charge generation arising from donor excitations is characterized with a rise time of ∼9 ps, while that from acceptor excitations shows a rise time of ∼18 ps. Temperature-dependent measurements further reveal notably distinct activation energies for these two charge generation pathways. Additionally, the two channels of charge generation can be substantially manipulated by altering the ratio of bulk to interfaces. These findings strongly suggest the presence of two distinct intermediate states: interfacial and intramoiety excitations. These states are crucial in mediating the transfer of electrons and holes, driving charge generation within OPV devices.

Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury.

Podocyte injury and loss are hallmarks of diabetic nephropathy (DN). However, the molecular mechanisms underlying these phenomena remain poorly understood. YAP (Yes-associated protein) is an important transcriptional coactivator that binds with various other transcription factors, including the TEAD family members (nuclear effectors of the Hippo pathway), that regulate cell proliferation, differentiation, and apoptosis. The present study found an increase in YAP phosphorylation at S127 of YAP and a reduction of nuclear YAP localization in podocytes of diabetic mouse and human kidneys, suggesting dysregulation of YAP may play a role in diabetic podocyte injury. Tamoxifen-inducible podocyte-specific Yap gene knockout mice (YappodKO) exhibited accelerated and worsened diabetic kidney injury. YAP inactivation decreased transcription factor WT1 expression with subsequent reduction of Tead1 and other well-known targets of WT1 in diabetic podocytes. Thus, our study not only sheds light on the pathophysiological roles of the Hippo pathway in diabetic podocyte injury but may also lead to the development of new therapeutic strategies to prevent and/or treat DN by targeting the Hippo signaling pathway.

Development of Platinum Complexes for Tumor Chemoimmunotherapy.

Platinum complexes are potential antitumor drugs in chemotherapy. Their impact on tumor treatment could be greatly strengthened by combining with immunotherapy. Increasing evidences indicate that the antitumor activity of platinum complexes is not limited to chemical killing effects, but also extends to immunomodulatory actions. This review introduced the general concept of chemoimmunotherapy and summarized the progress of platinum complexes as chemoimmunotherapeutic agents in recent years. Platinum complexes could be developed into inducers of immunogenic cell death, blockers of immune checkpoint, regulators of immune signaling pathway, and modulators of tumor immune microenvironment, etc. The synergy between chemotherapeutic and immunomodulatory effects reinforces the antitumor activity of platinum complexes, and helps them circumvent the drug resistance and systemic toxicity. The exploration of platinum complexes for chemoimmunotherapy may create new opportunities to revive the discovery of metal anticancer drugs.

The effects of community-based home health care on the physical and mental health of older adults with chronic diseases.

PURPOSE: This study aimed to explore the effects of community-based home health care (HHC) on the physical and mental health of older adults with chronic diseases in China. METHODS: The study data were retrieved from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey. Ordinary least squares regression model was used to assess the effects of community-based HHC on the health. Entropy balancing was used to test the robustness of the regression results. RESULTS: A total of 5571 older adults with chronic diseases were included. The results showed that older adults who had received community-based HHC reported significantly better self-rated health (coefficient = 0.051, 95%CI [0.004, 0.098]), less physical discomfort (coefficient = - 0.021, 95%CI [- 0.042, - 0.001]), lower depression scores (coefficient = - 0.263, 95%CI [- 0.490, - 0.037]), and lower anxiety scores (coefficient = - 0.233, 95%CI [- 0.379, - 0.088]) compared with those who had not received community-based HHC. Overall, community-based HHC conferred greater positive effects on the health of rural older adults, older adults with multiple chronic diseases, and older adults with low incomes. CONCLUSION: Community-based HHC was beneficial for improving self-rated health and reducing physical discomfort, depression, and anxiety in older adults with chronic diseases, thus improving their quality of life. It is important to promote its development nationwide in China.

Survival analysis of patients with extrahepatic cholangiocarcinoma: a nomogram for clinical and MRI features.

BACKGROUND: This study aimed to establish a predictive model to estimate the postoperative prognosis of patients with extrahepatic cholangiocarcinoma (ECC) based on preoperative clinical and MRI features. METHODS: A total of 104 patients with ECC confirmed by surgery and pathology were enrolled from January 2013 to July 2021, whose preoperative clinical, laboratory, and MRI data were retrospectively collected and examined, and the effects of clinical and imaging characteristics on overall survival (OS) were analyzed by constructing Cox proportional hazard regression models. A nomogram was constructed to predict OS, and calibration curves and time-dependent receiver operating characteristic (ROC) curves were employed to assess OS accuracy. RESULTS: Multivariate regression analyses revealed that gender, DBIL, ALT, GGT, tumor size, lesion's position, the signal intensity ratio of liver to paraspinal muscle (SIRLiver/Muscle), and the signal intensity ratio of spleen to paraspinal muscle (SIRSpleen/Muscle) on T2WI sequences were significantly associated with OS, and these variables were included in a nomogram. The concordance index of nomogram for predicting OS was 0.766, and the AUC values of the nomogram predicting 1-year and 2-year OS rates were 0.838 and 0.863, respectively. The calibration curve demonstrated good agreement between predicted and observed OS. 5-fold and 10-fold cross-validation show good stability of nomogram predictions. CONCLUSIONS: Our nomogram based on clinical, laboratory, and MRI features well predicted OS of ECC patients, and could be considered as a convenient and personalized prediction tool for clinicians to make decisions.

Machine learning-driven SERS analysis platform for rapid and accurate detection of precancerous lesions of gastric cancer.

A novel approach is proposed leveraging surface-enhanced Raman spectroscopy (SERS) combined with machine learning (ML) techniques, principal component analysis (PCA)-centroid displacement-based nearest neighbor (CDNN). This label-free approach can identify slight abnormalities between SERS spectra of gastric lesions at different stages, offering a promising avenue for detection and prevention of precancerous lesion of gastric cancer (PLGC). The agaric-shaped nanoarray substrate was prepared using gas-liquid interface self-assembly and reactive ion etching (RIE) technology to measure SERS spectra of serum from mice model with gastric lesions at different stages, and then a SERS spectral recognition model was trained and constructed using the PCA-CDNN algorithm. The results showed that the agaric-shaped nanoarray substrate has good uniformity, stability, cleanliness, and SERS enhancement effect. The trained PCA-CDNN model not only found the most important features of PLGC, but also achieved satisfactory classification results with accuracy, area under curve (AUC), sensitivity, and specificity up to 100%. This demonstrated the enormous potential of this analysis platform in the diagnosis of PLGC.

Correlation between immunotherapy biomarker PD-L1 expression and genetic alteration in patients with non-small cell lung cancer.

Programmed death-ligand 1 (PD-L1) has been widely used in immunotherapy evaluation of patients with non-small cell lung cancer (NSCLC). However, the effect is not particularly ideal, and the association between PD-L1 and genetic alterations requires more exploration. Here, we performed targeted next-generation sequencing and PD-L1 immunohistochemistry (IHC) testing for PD-L1 expression on both tumor cells (TCs) and tumor-infiltrating immune cells (ICs) in 1549 patients. Our studies showed that surgical method of resection was positively correlated with IC+, and a low tumor mutation burden (TMB) was negatively correlated with TC+. Furthermore, we found that EGFR was mutually exclusive with both ALK and STK11. In addition, the features between PD-L1 expression status and genomic alterations were characterized. These results suggest that clinical characteristics and molecular phenotypes are associated with PD-L1 expression signatures, which may provide novel insights for improving the efficiency of immune checkpoint inhibitors (ICIs) in immunotherapy.

Micrometer-Scale Carrier Transport in the Solid Film of Giant CdSe/CdS Nanocrystals Imaged by Transient Absorption Microscopy.

For the practical applications in solar cells and photodetectors, semiconductor colloidal nanocrystals (NCs) are assembled into a high-concentration film with carrier transport characteristics, the full understanding and effective control of which are critical for the achievement of high light-to-electricity conversion efficiencies. Here we have applied transient absorption microscopy to the solid film of giant CdSe/CdS NCs and discovered that at high pump fluences the carrier transport could reach a long distance of ∼2 µm within ∼30 ps after laser pulse excitation. This intriguing behavior is attributed to the metal-insulator transition and the associated bandlike transport, which are promoted by the enhanced electronic coupling among neighboring NCs with extended wave functions overlap of the excited-state charge carriers. Besides providing fundamental transport information in the regime of high laser pump fluences, the above findings shed light on the rational design of high-power light detecting schemes based on colloidal NCs.

Discrete Elemental Distributions inside a Single Mixed-Halide Perovskite Nanocrystal for the Self-Assembly of Multiple Quantum-Light Sources.

An in-depth understanding of the structure-property relationships in semiconductor mixed-halide perovskites is critical for their potential applications in various light-absorbing and light-emitting optoelectronic devices. Here we show that during the crystal growth of mixed-halide CsPbBr1.2I1.8 nanocrystals (NCs), abundant Ruddlesden-Popper (RP) plane stacking faults are formed to release the lattice strain. These RP planes hinder the exchange of halide species across them, resulting in the presence of multiple nanodomains with discrete mixed-halide compositions inside a single CsPbBr1.2I1.8 NC. Photoluminescence peaks from these pre-segregated nanodomains, whose correlated intensity and wavelength variations signify the interactions of coupled quantum dots within a single CsPbBr1.2I1.8 NC, can be simultaneously resolved at cryogenic temperature. Our findings thus point to a fascinating scenario in which a semiconductor nanostructure can be further divided into multiple quantum-light sources, the interaction and manipulation of which will promote novel photophysics to facilitate their potential applications in quantum information technologies.

Agonists and Inhibitors of the cGAS-STING Pathway.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is pivotal in immunotherapy. Several agonists and inhibitors of the cGAS-STING pathway have been developed and evaluated for the treatment of various diseases. The agonists aim to activate STING, with cyclic dinucleotides (CDNs) being the most common, while the inhibitors aim to block the enzymatic activity or DNA binding ability of cGAS. Meanwhile, non-CDN compounds and cGAS agonists are also gaining attention. The omnipresence of the cGAS-STING pathway in vivo indicates that its overactivation could lead to undesired inflammatory responses and autoimmune diseases, which underscores the necessity of developing both agonists and inhibitors of the cGAS-STING pathway. This review describes the molecular traits and roles of the cGAS-STING pathway and summarizes the development of cGAS-STING agonists and inhibitors. The information is supposed to be conducive to the design of novel drugs for targeting the cGAS-STING pathway.

Tandem Synergistic Effect of Cu-In Dual Sites Confined on the Edge of Monolayer CuInP2 S6 toward Selective Photoreduction of CO2 into Multi-Carbon Solar Fuels.

One-unit-cell, single-crystal, hexagonal CuInP2 S6 atomically thin sheets of≈0.81 nm in thickness was successfully synthesized for photocatalytic reduction of CO2 . Exciting ethene (C2 H4 ) as the main product was dominantly generated with the yield-based selectivity reaching ≈56.4 %, and the electron-based selectivity as high as ≈74.6 %. The tandem synergistic effect of charge-enriched Cu-In dual sites confined on the lateral edge of the CuInP2 S6 monolayer (ML) is mainly responsible for efficient conversion and high selectivity of the C2 H4 product as the basal surface site of the ML, exposing S atoms, can not derive the CO2 photoreduction due to the high energy barrier for the proton-coupled electron transfer of CO2 into *COOH. The marginal In site of the ML preeminently targets CO2 conversion to *CO under light illumination, and the *CO then migrates to the neighbor Cu sites for the subsequent C-C coupling reaction into C2 H4 with thermodynamic and kinetic feasibility. Moreover, ultrathin structure of the ML also allows to shorten the transfer distance of charge carriers from the interior onto the surface, thus inhibiting electron-hole recombination and enabling more electrons to survive and accumulate on the exposed active sites for CO2 reduction.

Room-temperature epitaxial welding of 3D and 2D perovskites.

Formation of epitaxial heterostructures via post-growth self-assembly is important in the design and preparation of functional hybrid systems combining unique properties of the constituents. This is particularly attractive for the construction of metal halide perovskite heterostructures, since their conventional solution synthesis usually leads to non-uniformity in composition, crystal phase and dimensionality. Herein, we demonstrate that a series of two-dimensional and three-dimensional perovskites of different composition and crystal phase can form epitaxial heterostructures through a ligand-assisted welding process at room temperature. Using the CsPbBr3/PEA2PbBr4 heterostructure as a demonstration, in addition to the effective charge and energy transfer across the epitaxial interface, localized lattice strain was observed at the interface, which was extended to the top layer of the two-dimensional perovskite, leading to multiple new sub-bandgap emissions at low temperature. Given the versatility of our strategy, unlimited hybrid systems are anticipated, yielding composition-, interface- and/or orientation-dependent properties.

Alcohol increases treatment failure for Helicobacter pylori eradication in Asian populations.

BACKGROUND AND AIM: Whether alcohol intake is associated with Helicobacter pylori (H. pylori) eradication failure remains controversial, and this meta-analysis was aimed at investigating the effect of alcohol on the risk of H. pylori eradication failure. METHODS: Relevant studies were systematically screened for and retrieved from PubMed and Web of Science (updated to January 2022), and relevant references were manually reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup, publication bias, and sensitivity analyses were also conducted. RESULTS: A total of 40 studies were included in the meta-analysis. No significant association was found between alcohol consumption and the risk of H. pylori eradication failure (OR = 1.09, 95% CI, 0.94-1.26). However, in subgroup analyses stratified by region, a positive association was found in Asian patients (OR = 1.23, 95% CI, 1.03-1.47). In Asian patients, alcohol consumption was associated with the risk of H. pylori eradication failure when the duration of therapy was > 7 days (OR = 1.17, 95% CI, 1.10-1.25), when the treatment regimen included nitroimidazoles (OR = 1.16, 95% CI, 1.09-1.24), and when patients were treated with bismuth-containing quadruple therapy (OR = 1.17, 95% CI, 1.10-1.25). Alcohol intake > 40 g/day was associated with H. pylori eradication failure (OR = 3.17, 95% CI, 1.56-6.41). Moreover, in Asian patients who were administered a vonoprazan (VPZ)-based therapy regimen, alcohol consumption had no effect on H. pylori eradication rates (OR = 1.73, 95% CI, 0.98-3.05). CONCLUSION: Our meta-analysis clearly showed that a higher daily alcohol intake was associated with a higher risk of H. pylori eradication failure in Asian populations. Moreover, a VPZ-based treatment regimen can prevent this effect.

Serum potassium in elderly heart failure patients as a predictor of readmission within 1 year.

Blood potassium levels are associated with adverse outcomes in patients with congestive heart failure (HF). However, it is unclear whether there are differences in outcome events in elderly patients with different blood potassium levels at the time of emergency readmission within 1 year. This study used data from patients hospitalized with HF, integrating electronic medical records from the PhysioNet restricted health data database and external outcome data. We conducted a retrospective study of HF patients aged 60 years and older, using baseline data, comorbidities, laboratory tests, and medication use as covariates to analyze the effect of serum potassium levels on outcome events, with the primary outcome being readmission within 1 year. A priori was used to calculate the sample size, and this retrospective cohort study included a total of 788 elderly HF patients, of whom 20.3% had hypokalaemia (K+ < 3.5 mmol/L) and 14.7% had hyperkalemia (K+ > 4.7 mmol/L). According to a multivariate Cox regression model, patients with hyperkalemia had a shorter time interval between readmissions within 1 year, with a hazard ratio (HR) and its 95% CI of 1.134 (1.006-1.279). Three models were used to analyze patients with different blood potassium levels and, after correction, the high potassium group was at high risk relative to the low and normal groups, with significant differences in outcome events, with HRs and their 95% CI of 1.266 (1.03-1.557), 1.245 (1.01-1.534), and 1.439 (1.142-1.812), respectively. The robustness of the model was also demonstrated by competing risk models with subgroup analysis, showing that blood potassium levels had a stable effect on outcome events and were not altered by covariates (age, sex, diabetes, chronic kidney disease, NT-proBNP, high-sensitivity troponin, and glomerular filtration rate). The results show that high blood potassium levels are associated with the outcome event of readmission within 1 year in elderly patients with HF. Blood potassium levels at the time of the first hospitalization may therefore be a valuable predictor.

Quantized Exciton Motion and Fine Energy-Level Structure of a Single Perovskite Nanowire.

The quantum-confinement effect profoundly influences the exciton energy-level structures and recombination dynamics of semiconductor nanostructures but remains largely unexplored in traditional one-dimensional nanowires mainly due to their poor optical qualities. Here, we show that in defect-tolerant perovskite material of highly luminescent CsPbBr3 nanowires, the exciton's center-of-mass motion perpendicular to the axial direction is severely confined. This is reflected in the two sets of photoluminescence spectra emitted from a single CsPbBr3 nanowire, each of which consists of doublet peaks with linear polarizations perpendicular and parallel to the axial direction. Moreover, different exciton states can be mixed by the Rashba spin-orbit coupling effect, resulting in two single photoluminescence peaks with linear polarizations both along the nanowire axis. The above findings mark the emergence of an ideal platform for the exploration of intrinsic one-dimensional exciton photophysics and optoelectronics, thus bridging the long-missing research gap between the well-studied two- and zero-dimensional semiconductor nanostructures.

On the ramifications of airspace bans in aero-political conflicts: Towards a country importance ranking.

The aviation industry is facing highly volatile developments in the recent years: Following a steady growth phase with prosperous projections, the COVID-19 pandemic has hit the aviation system rather hard. While having gradually entered a recovery process in the years 2021 and 2022, with load factors close to those in the year 2019, the airspace bans between Russia, Europe, and other regions in the world, as part of the ongoing conflict centered around Russia and Ukraine, threaten the orderly operation of flights. This study explores the byproducts and potential impact of airspace bans on the aviation system and its stakeholders, by deriving a ranking of country importance and how they have the potential to influence our aviation system. While being rooted in the analysis of the Russian-Ukrainian conflict, our framework is built up in a generic way and computes an overall country importance metric. We believe that our study contributes to the better understanding of the consequences airspace bans have on our society and the severe needs for effective policies and regulations of such emerging forms of conflict resolution.

Overcoming Cancer Resistance to Platinum Drugs by Inhibiting Cholesterol Metabolism.

Drug resistance is a serious challenge for platinum anticancer drugs. Platinum complexes may get over the drug resistance via a distinct mechanism of action. Cholesterol is a key factor contributing to the drug resistance. Inhibiting cellular cholesterol synthesis and uptake provides an alternative strategy for cancer treatment. Platinum(IV) complexes FP and DFP with fenofibric acid as axial ligand(s) were designed to combat the drug resistance through regulating cholesterol metabolism besides damaging DNA. In addition to producing reactive oxygen species and active platinum(II) species to damage DNA, FP and DFP inhibited cellular cholesterol accumulation, promoted cholesterol efflux, upregulated peroxisome proliferator-activated receptor alpha (PPARα), induced caspase-1 activation and gasdermin D (GSDMD) cleavage, thus leading to both apoptosis and pyroptosis in cancer cells. The reduction of cholesterol significantly relieved the drug resistance of cancer cells. The double-acting mechanism gave the complexes strong anticancer activity in vitro and in vivo, particularly against cisplatin-resistant cancer cells.

Platinum-Based TREM2 Inhibitor Suppresses Tumors by Remodeling the Immunosuppressive Microenvironment.

Triggering receptor expressed on myeloid cells-2 (TREM2) is a key pro-tumorigenic marker of tumor-infiltrating macrophages, showing potent immunosuppressive activity in tumor microenvironment. A platinum(IV) complex OPA derived from oxaliplatin (OP) and artesunate (ART) exhibited direct cytotoxicity against human colon cancer cells and immunomodulatory activity to inhibit TREM2 on macrophages in vitro and vivo. Furthermore, OPA deterred the tumor growth in mouse models bearing MC38 colorectal tumor by reducing the number of CD206+ and CX3 CR1+ immunosuppressive macrophages; it also promoted the expansion and infiltration of immunostimulatory dendritic, cytotoxic T, and natural killer cells. OPA is the first small-molecular TREM2 inhibitor capable of relieving immunosuppressive tumor microenvironment and enhancing chemical anticancer efficiency of a platinum drug, thus showing typical characteristics of a chemoimmunotherapeutic agent.

TAZ is important for maintenance of the integrity of podocytes.

The podocyte is an important component of the glomerular filtration barrier, and maintenance of the integrity of its highly specified structure and function is critical for normal kidney function. Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are two crucial effectors of the Hippo signaling pathway, and recent studies have shown that podocyte-specific YAP deletion causes podocyte apoptosis and the development of focal segmental glomerulosclerosis followed by progressive renal failure. In the present study, we investigated a potential role of the YAP paralog TAZ in podocytes. TAZ was found to be constitutively active in podocytes, and mice with podocyte-specific deletion of TAZ (TazpodKO) developed proteinuria starting at 4 wk of age and had increased podocyte apoptosis. Using primary cultured podocytes or immortalized mouse podocytes from Tazflox/flox mice, we found that TAZ is a transcriptional activator for TEAD-dependent expression of synaptopodin, zonula occludens-1, and zonula occludens-2. This is the first study to determine that TAZ plays an important role in the maintenance of the structure and function of podocytes.NEW & NOTEWORTHY Podocytes play an important role in maintaining the integrity of the structure and function of the kidney. We observed that mice with selective deletion of transcriptional coactivator with PDZ-binding motif (TAZ) in podocytes developed proteinuria. TAZ is constitutively active and critical for expression of synaptopodin, zonula occludens-1, and zonula occludens-2 in podocytes. The findings of this study implicate TAZ as an important mediator of podocyte structural integrity and provide further insights into the role of Hippo-Yes-associated protein/TAZ in podocyte biology.