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Semiconductor mixed-halide perovskites featured with a tunable energy bandgap are ideal candidates for light absorbers in tandem solar cells as well as fluorescent materials in light-emitting diodes and nanoscale lasers. These device advancements are currently hindered by the light-induced phase segregation effect, whereby ion migration would yield smaller-bandgap domains with red-shifted photoluminescence. Here we show that upon laser excitation all-inorganic mixed-halide nanocrystals unexpectedly exhibit a blue shift in the photoluminescence peak that can revert back in the dark, thus depicting the processes of ion migration out of and back to the originally excited nanocrystals. Interestingly, this reversible photoluminescence shift can also be induced by electrical biasing of mixed-halide nanocrystals without the injection of charge carriers. The above findings suggest that it is the local electric field that breaks the ionic bonds in mixed-halide nanocrystals, which could be a universal origin for light-induced phase segregation observed in other mixed-halide perovskite materials. Mixed-halide perovskites possess excellent semiconductor properties but suffer severely from notorious light-induced phase segregation effect. Here Zhang et al. employ simple photoluminescence measurements to link the effect to the local electric field induced ion migration process.

0D perovskites have gained much attention in recent years due to their fascinating properties derived from their peculiar structure with isolated metal halide octahedra or metal halide clusters. However, the systematic discussion on the crystal and electronic structure of 0D perovskites to further understand their photophysical characteristics and the comprehensive overview of 0D perovskites for their further applications are still lacking. In this review, the unique crystal and electronic structure of 0D perovskites and their diverse properties are comprehensively analyzed, including large bandgaps, high exciton binding energy, and largely Stokes‐shifted broadband emissions from self‐trapped excitons. Furthermore, the photoluminescence regulation are discussed. Then, the various synthetic methods for 0D perovskite single crystals, nanocrystals, and thin films are comprehensively summarized. Finally, the emerging applications of 0D perovskites to light‐emitting diodes, solar cells, detectors, and some others are illustrated, and the outlook on future research in the field is also provided. The unique crystal and electronic structure of 0D perovskites and their photoluminescence mechanism are comprehensively analyzed in this review. The different synthetic methods for 0D perovskite crystals and thin films, and their diverse applications are also discussed. In addition, the outlook on future research in the field is provided.

Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases 1 , but the systematic identification of such individuals remains a challenge. Here we performed whole-genome sequencing analyses to characterize genetic variation in 235 individuals (from 209 families) with ataxia-telangiectasia, a severely debilitating and life-threatening recessive genetic disorder 2 , 3 , yielding a complete molecular diagnosis in almost all individuals. We developed a predictive taxonomy to assess the amenability of each individual to splice-switching ASO intervention; 9% and 6% of the individuals had variants that were ‘probably’ or ‘possibly’ amenable to ASO splice modulation, respectively. Most amenable variants were in deep intronic regions that are inaccessible to exon-targeted sequencing. We developed ASOs that successfully rescued mis-splicing and ATM cellular signalling in patient fibroblasts for two recurrent variants. In a pilot clinical study, one of these ASOs was used to treat a child who had been diagnosed with ataxia-telangiectasia soon after birth, and showed good tolerability without serious adverse events for three years. Our study provides a framework for the prospective identification of individuals with genetic diseases who might benefit from a therapeutic approach involving splice-switching ASOs. Whole-genome sequencing analyses in a cohort of individuals with ataxia-telangiectasia are used to identify genetic variants that might be amenable to treatment with splice-switching antisense oligonucleotides (ASOs), and develop ASOs with therapeutic potential.

Developing heterogeneous photocatalysts for the applications in harsh conditions is of high importance but challenging. Herein, by converting the imine linkages into quinoline groups of triphenylamine incorporated covalent organic frameworks (COFs), two photosensitive COFs, namely TFPA-TAPT-COF-Q and TFPA-TPB-COF-Q, are successfully constructed. The obtained quinoline-linked COFs display improved stability and photocatalytic activity, making them suitable photocatalysts for photocatalytic reactions under harsh conditions, as verified by the recyclable photocatalytic reactions of organic acid involving oxidative decarboxylation and organic base involving benzylamine coupling. Under strong oxidative condition, the quinoline-linked COFs show a high efficiency up to 11831.6 μmol·g −1 ·h −1 and a long-term recyclable usability for photocatalytic production of H 2 O 2 , while the pristine imine-linked COFs are less catalytically active and easily decomposed in these harsh conditions. The results demonstrate that enhancing the linkage robustness of photoactive COFs is a promising strategy to construct heterogeneous catalysts for photocatalytic reactions under harsh conditions. The development of heterogeneous photocatalysts applicable under harsh conditions is challenging. Here the authors report the conversion of imine linkages into quinoline groups in triphenylamine incorporated photosensitive covalent organic frameworks to develop robust heterogeneous photocatalysts for photocatalytic applications in harsh conditions.

There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention. Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study. ClinicalTrials.gov NCT02530385.

Carbon-bound boronic acids and their esters are widely used as coupling partners to make carbon-carbon bonds. More recently, these chemicals have garnered pharmaceutical interest in their own right. Li et al. report a versatile nickel-catalyzed process to replace carboxylic acids with boronate esters by using a phthalimide activator. The reaction is well suited to late-stage modification of complex molecules. The authors used the approach to produce a potent in vitro inhibitor of human neutrophil elastase, a target of interest in treating inflammatory lung diseases. Science , this issue p. eaam7355 Nickel catalyzes replacement of carboxylic acid groups with boronic acids and esters in a wide variety of compounds. The widespread use of alkyl boronic acids and esters is frequently hampered by the challenges associated with their preparation. We describe a simple and practical method to rapidly access densely functionalized alkyl boronate esters from abundant carboxylic substituents. This broad-scope nickel-catalyzed reaction uses the same activating principle as amide bond formation to replace a carboxylic acid moiety with a boronate ester. Application to peptides allowed expedient preparations of α-amino boronic acids, often with high stereoselectivity, thereby facilitating synthesis of the alkyl boronic acid drugs Velcade and Ninlaro as well as a boronic acid version of the iconic antibiotic vancomycin. The reaction also enabled the discovery and extensive biological characterization of potent human neutrophil elastase inhibitors, which offer reversible covalent binding properties.

Forkheadbox protein 3 (FOXP3), initially identified as a key transcription factor for regulatory T cells (Treg cells), was also expressed in many tumors including pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC progression remains elusive. In this study, we utilized 120 PDAC tissues after radical resection to detect cancer-FOXP3 and Treg cells by immunohistochemistry and evaluated clinical and pathological features of these patients. Cancer-FOXP3 was positively correlated with Treg cells accumulation in tumor tissues derived from PDAC patients. In addition, high cancer-FOXP3 expression was associated with increased tumor volumes and poor prognosis in PDAC especially combined with high levels of Treg cells. Overexpression of cancer-FOXP3 promoted the tumor growth in immunocompetent syngeneic mice but not in immunocompromised or Treg cell-depleted mice. Furthermore, CCL5 was directly trans-activated by cancer-FOXP3 and promoted the recruitment of Treg cells from peripheral blood to the tumor site in vitro and in vivo . This finding has been further reinforced by the evidence that Treg cells recruitment by cancer-FOXP3 was impaired by neutralization of CCL5, thereby inhibiting the growth of PDAC. In conclusion, cancer-FOXP3 serves as a prognostic biomarker and a crucial determinant of immunosuppressive microenvironment via recruiting Treg cells by directly trans-activating CCL5. Therefore, cancer-FOXP3 could be used to select patients with better response to CCL5/CCR5 blockade immunotherapy.

On 15 January 2022, the Hunga Tonga‐Hunga Ha'apai (HT) eruption injected SO2 and water into the middle stratosphere. The SO2 is rapidly converted to sulfate aerosols. The aerosol and water vapor anomalies have persisted in the Southern Hemisphere throughout 2022. The water vapor anomaly increases the net downward IR radiative flux whereas the aerosol layer reduces the direct solar forcing. The direct solar flux reduction is larger than the increased IR flux. Thus, the net tropospheric forcing will be negative. The changes in radiative forcing peak in July and August and diminish thereafter. Scaling to the observed cooling after the 1991 Pinatubo eruption, HT would cool the 2022 Southern Hemisphere's average surface temperatures by less than 0.037°C. Plain Language Summary The Hunga Tonga‐Hunga Ha'apai submarine volcanic eruption on 15 January 2022 produced aerosol and water vapor plumes in the stratosphere. These plumes have persisted mostly in the Southern Hemisphere throughout 2022. Enhanced tropospheric warming due to the added stratospheric water vapor is offset by the larger stratospheric aerosol attenuation of solar radiation. The change in the radiative flux could result in a very slight cooling in Southern Hemisphere surface temperatures. Key Points Following the January 2022 Hunga‐Tonga eruption, both aerosols and water vapor increased in the stratosphere The stratospheric water vapor increases the net downward radiative flux up to 0.3 W/m2 and aerosols reduce the solar flux up to ∼1.5 W/m2 The reduction in radiative forcing by the Hunga‐Tonga eruption will slightly cool the Southern Hemisphere in 2022

SummaryOur study demonstrated a high incidence of recollapse of the augmented vertebrae after PVP treatment for OVCFs. A risk score based on all significant factors can predict the rate of recollapse and gain clinical benefits to prevent recollapse in patients at high risk.BackgroundRecollapse of the augmented vertebrae after percutaneous vertebroplasty (PVP) treatment for osteoporotic vertebral compression fractures (OVCFs) has obtained much attention. However, little is known about risk factors and score for recollapse of the augmented vertebrae.ObjectiveTo determine risk factors and furthermore develop a risk score related to recollapse of the augmented vertebrae after PVP treatment for OVCFs.MethodsPatients who were treated with PVP for single OVCFs and met this study’s inclusion criteria were retrospectively reviewed. The follow-up period was at least 2 years. Associations of recollapse with co-variates (age, gender, bone mass density [BMD] with a T-score, fracture level, intravertebral cleft [IVC], fracture type, cement volume, cement leakage, leakage into a disc, cement distribution pattern, Non-PMMA-endplate-contact [NPEC], preoperative fracture severity, reduction rate [RR], reduction angle [RA]) were analyzed and a risk score for recollapse was further developed to predict recollapse.ResultsA total of 152 patients were included. Recollapse group was found in 42 (27.6%) patients. Preoperative IVC, solid lump cement distribution pattern, more RR (a cutoff value of 7%) and larger RA (a cutoff value of 3°) was significantly associated with increased risk for recollapse of the augmented vertebrae. A risk score was developed based on the number of risk factors present in each patient. Patients with a score of 4 had an approximately ninefold increased risk of developing recollapse over patients with a score of 0. The receiver operating characteristic curve of the risk score generated an area under the curve of 0.899 (95% CI 0.642–0.836, P = 0.000).ConclusionA risk score based on preoperative IVC, cement distribution pattern, reduction rate, and reduction angle predicts the rate of recollapse. Additional studies should aim to validate this score and inspect clinical benefits of recollapse prophylaxis in patients at high risk.