LORIS robustly predicts patient outcomes with immune checkpoint blockade therapy using common clinical, pathologic and genomic features.

Despite the revolutionary impact of immune checkpoint blockade (ICB) in cancer treatment, accurately predicting patient responses remains challenging. Here, we analyzed a large dataset of 2,881 ICB-treated and 841 non-ICB-treated patients across 18 solid tumor types, encompassing a wide range of clinical, pathologic and genomic features. We developed a clinical score called LORIS (logistic regression-based immunotherapy-response score) using a six-feature logistic regression model. LORIS outperforms previous signatures in predicting ICB response and identifying responsive patients even with low tumor mutational burden or programmed cell death 1 ligand 1 expression. LORIS consistently predicts patient objective response and short-term and long-term survival across most cancer types. Moreover, LORIS showcases a near-monotonic relationship with ICB response probability and patient survival, enabling precise patient stratification. As an accurate, interpretable method using a few readily measurable features, LORIS may help improve clinical decision-making in precision medicine to maximize patient benefit. LORIS is available as an online tool at https://loris.ccr.cancer.gov/ .

Ultrasound-guided percutaneous high-frequency irreversible electroporation in porcine livers using four electrode needles: A feasibility and safety study.

BACKGROUND: Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high-frequency irreversible electroporation (H-FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound-guided percutaneous H-FIRE using four electrode needles in porcine livers. METHODS: Twelve experimental pigs underwent percutaneous H-FIRE ablation using a compound steep-pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast-enhanced ultrasound (CEUS), contrast-enhanced magnetic resonance imaging (MRI), and hematoxylin-eosin staining were performed to evaluate the ablation performance. RESULTS: Ultrasound-guided percutaneous H-FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H-FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. CONCLUSIONS: This study demonstrated the feasibility and safety of ultrasound-guided percutaneous H-FIRE ablation in porcine livers in vivo, and proposed a four-needle method to optimize its clinical application.

Three new griseofulvin derivatives from Aureobasidium pullulans.

Three new griseofulvin derivatives, griseofulvinoside A-C (1-3), were isolated from the ethyl acetate extract of the solid fermentation product of Aureobasidium pullulans. Their structures were elucidated based on extensive spectroscopic data analysis of MS, 1D and 2D NMR. The antifungal activities of new compounds were evaluated against four phytopathogenic fungi in vitro, and all test compounds demonstrated inhibitory effects. Among them, compound 2 exhibited the most potent activities against the four selected phytopathogenic fungi with inhibitory rates ranging from 40.2 to 75.8% at 0.2 mg/mL.

Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Effectiveness of a 10-year continuous reduction of controlled-release nitrogen fertilizer on production, nitrogen loss and utilization of double-cropping rice.

Considerable literature has demonstrated the advantage of controlled-release nitrogen (CRN) fertilizer in improving crop productivity. However, few researches have explored the long-term impacts of using CRN fertilizers as alternative to common urea on production and N utilization in double-cropping paddy. To address this gap, our study utilized a database derived from a 10-year field experiment from 2013 to 2022. During early and late rice seasons, compared to common urea (early rice, 150 kg hm-2; late rice, 180 kg hm-2), CRN fertilizer (150 kg hm-2; 180 kg hm-2) input significantly increased yield by 7.4 %, and 11.7 %, as well as N use efficiency (NUE) from 23.0 % and 24.6 % to 33.0 % and 37.5 %, respectively. CRN application significantly reduced N losses, evidenced by decrease in runoff (23.1 % and 19.4 %), leaching (12.7 % and 12.1 %), ammonia volatilization (28.9 % and 30.2 %), and N2O emissions (10.4 % and 16.1 %). A reduction of 10 % in CRN fertilizer input maintained yield. Compared with normal amount, reducing 10, 20, and 30 % CRN input increased NUE by 7.0-7.6 %, 7.3-7.4 %, and 11.6-12.6 %; reduced runoff loss by 16.1-17.9 %, 27.9-30.7 %, and 35.0-37.2 %; decreased leaching loss by 7.6-12.8 %, 18.1-22.6 %, and 26.5-31.4 %; decreased ammonia volatilization by 9.9-12.3 %, 16.3-22.7 %, and 23.2-29.3 %, and decreased N2O loss by 7.8-13.3 %, 12.8-32.8 %, and 20.3-36.9 %, respectively. Soils with CRN input showed higher total and inorganic N contents than the soils with common urea, and the content increased in parallel with CRN fertilizer input. Soil N content and N runoff loss were significantly related to yield and N uptake, and N runoff and leaching losses were significantly related to NUE. These results support the sustainable use of CRN fertilizers as a viable alternative to common urea, indicating that application rate of 135 and 162 kg N hm-2 of early and late rice, respectively, maintain yield and enhance N utilization in double-season paddy of southern China.

Enhanced Homogeneity of Moiré Superlattices in Double-Bilayer WSe2 Homostructure.

Moiré superlattices have emerged as a promising platform for investigating and designing optically generated excitonic properties. The electronic band structure of these systems can be qualitatively modulated by interactions between the top and bottom layers, leading to the emergence of new quantum phenomena. However, the inhomogeneities present in atomically thin bilayer moiré superlattices created by artificial stacking have hindered a deeper understanding of strongly correlated electron properties. In this work, we report the fabrication of homogeneous moiré superlattices with controllable twist angles using a 2L-WSe2/2L-WSe2 homostructure. By adding extra layers, we provide additional degrees of freedom to tune the optical properties of the moiré superlattices while mitigating the nonuniformity problem. The presence of an additional bottom layer acts as a buffer, reducing the inhomogeneity of the moiré superlattice, while the encapsulation effect of the additional top and bottom WSe2 monolayers further enhances the localized moiré excitons. Our observations of alternating circularly polarized photoluminescence confirm the existence of moiré excitons, and their characteristics were further confirmed by theoretical calculations. These findings provide a fundamental basis for studying moiré potential correlated quantum phenomena and pave the way for their application in quantum optical devices.

Pressure-Induced Dynamic Tuning of Interlayer Coupling in Twisted WSe2/WSe2 Homobilayers.

Moiré superlattices induced by twisted van der Waals (vdW) heterostructures or homostructures have recently gained significant attention due to their potential to generate exotic strong-correlation electronic and phonon phenomena. However, the lack of dynamic tuning for interlayer coupling of moiré superlattices hinders a thorough understanding and development of the moiré correlation state. Here, we present a dynamic tuning method for twisted WSe2/WSe2 homobilayers using a diamond anvil cell (DAC). We demonstrate the powerful tuning of interlayer coupling and observe an enhanced response to pressure for interlayer breathing modes and the rapid descent of indirect excitons in twisted WSe2/WSe2 homobilayers. Our findings indicate that the introduction of a moiré superlattice for WSe2 bilayers gives rise to hybridized excitons, which lead to the different pressure-evolution exciton behaviors compared to natural WSe2 bilayers. Our results provide a novel understanding of moiré physics and offer an effective method to tune interlayer coupling of moiré superlattices.

[Clinical and genetic analysis of a child with X-linked dominant Alport syndrome].

OBJECTIVE: To investigate the clinical features and genetic variant of a child with X-linked dominant Alport syndrome (XLAS). METHODS: A child who had presented at the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data of the child was collected. Next generation sequencing (NGS) was carried out for the child. Candidate variants were validated by Sanger sequencing of his family members. RESULTS: The child, a 12-year-old boy, had mainly manifested gross hematuria, proteinuria, nephrotic syndrome, and progressive renal impairment in conjunct with hearing loss. Kidney biopsy has revealed uneven glomerular basement membrane thickness. DNA sequencing revealed that the child and his mother have both carried a heterozygous c.2632G>A (p.G878R) variant of the COL4A5 gene, for which his father and brother were of the wild type. This variant was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PS1+PM1+PM2_Supporting+PP3). CONCLUSION: The maternally derived hemizygous c.2632G>A (p.G878R) variant of the COL4A5 gene probably underlay the XLAS in this child. Above finding has enriched the mutational spectrum of the COL4A5 gene.

Satellite record reveals 1960s acceleration of Totten Ice Shelf in East Antarctica.

Wilkes Land and Totten Glacier (TG) in East Antarctica (EA) have been losing ice mass significantly since 1989. There is a lack of knowledge of long-term mass balance in the region which hinders the estimation of its contribution to global sea level rise. Here we show that this acceleration trend in TG has occurred since the 1960s. We reconstruct ice flow velocity fields of 1963-1989 in TG from the first-generation satellite images of ARGON and Landsat-1&4, and build a five decade-long record of ice dynamics. We find a persistent long-term ice discharge rate of 68 ± 1 Gt/y and an acceleration of 0.17 ± 0.02 Gt/y2 from 1963 to 2018, making TG the greatest contributor to global sea level rise in EA. We attribute the long-term acceleration near grounding line from 1963 to 2018 to basal melting likely induced by warm modified Circumpolar Deep Water. The speed up in shelf front during 1973-1989 was caused by a large calving front retreat. As the current trend continues, intensified monitoring in the TG region is recommended in the next decades.

Observation of optical anisotropy and a linear dichroism transition in layered silicon phosphide.

The investigation of in-plane two-dimensional (2D) anisotropic materials has garnered significant attention due to their exceptional electronic, optical, and mechanical characteristics. The anisotropic optical properties and angle-dependent photodetectors based on 2D anisotropic materials have been extensively studied. However, novel in-plane anisotropic materials still need to be explored to satisfy for distinct environments and devices. Here, we report the remarkable anisotropic behavior of excitons and demonstrate a unique linear-dichroism transition of absorption between ultraviolet and visible light in layered silicon phosphide (SiP) through the analysis of polarization photoluminescence (PL) and absorbance spectra. Its high absorption linear dichroism ratio of 1.16 at 388 nm, 1.15 at 532 nm, and 1.19 at 733 nm is revealed, suggesting the brilliant non-isotropic responses. The robust periodic variation of the A1 and A2 Raman modes in 2D SiP materials allows for the determination of their crystal orientation. Furthermore, the presence of indirect excitons with phonon sidebands in the temperature-dependent PL spectra exhibits non-monotonic energy shifts with increasing temperature, which is attributed to an enhanced electron-phonon interaction and thermal expansion. Our findings provide valuable insights into the fundamental physical properties of layered SiP and offer guidelines for designing polarization-sensitive photodetectors and angle-dependent devices based on 2D anisotropic materials.

Optimizing cancer immunotherapy response prediction by tumor aneuploidy score and fraction of copy number alterations.

Identifying patients that are likely to respond to cancer immunotherapy is an important, yet highly challenging clinical need. Using 3139 patients across 17 different cancer types, we comprehensively studied the ability of two common copy-number alteration (CNA) scores-the tumor aneuploidy score (AS) and the fraction of genome single nucleotide polymorphism encompassed by copy-number alterations (FGA)-to predict survival following immunotherapy in both pan-cancer and individual cancer types. First, we show that choice of cutoff during CNA calling significantly influences the predictive power of AS and FGA for patient survival following immunotherapy. Remarkably, by using proper cutoff during CNA calling, AS and FGA can predict pan-cancer survival following immunotherapy for both high-TMB and low-TMB patients. However, at the individual cancer level, our data suggest that the use of AS and FGA for predicting immunotherapy response is currently limited to only a few cancer types. Therefore, larger sample sizes are needed to evaluate the clinical utility of these measures for patient stratification in other cancer types. Finally, we propose a simple, non-parameterized, elbow-point-based method to help determine the cutoff used for calling CNAs.

Microglial Galectin3 enhances endothelial metabolism and promotes pathological angiogenesis via Notch inhibition by competitively binding to Jag1.

Microglia were considered as immune cells in inflammation until their angiogenic role was widely understood. Although the pro-inflammatory role of microglia in retinal angiogenesis has been explored, little is known about its role in pro-angiogenesis and the microglia-endothelia interaction. Here, we report that galectin-3 (Gal3) released by activated microglia functions as a communicator between microglia and endothelia and competitively binds to Jag1, thus inhibiting the Notch signaling pathway and enhancing endothelial angiogenic metabolism to promote angiogenesis. These results suggest that Gal3 may be a novel and effective target in the treatment of retinal angiogenesis.

Strain-tunable valley polarization and localized excitons in monolayer WSe2.

Monolayer transition metal dichalcogenides (TMDs) have a crystalline structure with broken spatial inversion symmetry, making them promising candidates for valleytronic applications. However, the degree of valley polarization is usually not high due to the presence of intervalley scattering. Here, we use the nanoindentation technique to fabricate strained structures of WSe2 on Au arrays, thus demonstrating the generation and detection of strained localized excitons in monolayer WSe2. Enhanced emission of strain-localized excitons was observed as two sharp photoluminescence (PL) peaks measured using low-temperature PL spectroscopy. We attribute these emerging sharp peaks to excitons trapped in potential wells formed by local strains. Furthermore, the valley polarization of monolayer WSe2 is modulated by a magnetic field, and the valley polarization of strained localized excitons is increased, with a high value of up to approximately 79.6%. Our results show that tunable valley polarization and localized excitons can be realized in WSe2 monolayers, which may be useful for valleytronic applications.

Genome Re-Annotation and Transcriptome Analyses of Sanghuangporus sanghuang.

Sanghuangporus sanghuang, the generic type of Sanghuangporus belonging to Hymenochaetaceae, is a precious medicinal wood-inhabiting macrofungus with high commercial potential. To facilitate the medicinal utilization of this fungal resource, transcriptome sequences are newly generated from S. sanghuang strain MS2. In association with the previously generated genome sequences from the same strain by our lab and all available fungal homologous protein sequences in the UniProtKB/Swiss-Prot Protein Sequence Database, a new methodology was employed for genome assembly and annotation. A total of 13,531 protein-coding genes were identified from the new version of the genome of S. sanghuang strain MS2 with a complete BUSCOs of 92.8%, which indicates a remarkable improvement in the accuracy and completeness of the genome assembly. In general, more genes involved in medicinal functions were annotated compared with the original version of the genome annotation, and most of these genes were also found in the transcriptome data of the currently sampled growth period. Given the above, the current genomic and transcriptomic data provides valuable insights into the evolution and metabolites analysis of S. sanghuang.

Van der Waals Heterostructure Mid-Infrared Emitters with Electrically Controllable Polarization States and Spectral Characteristics.

Modern infrared (IR) microscopy, communication, and sensing systems demand control of the spectral characteristics and polarization states of light. Typically, these systems require the cascading of multiple filters, polarization optics, and rotating components to manipulate light, inevitably increasing their sizes and complexities. Here, we report two-terminal mid-infrared (mid-IR) emitters, in which tuning the polarity of the applied bias can switch their emission peak wavelengths and linear polarization states along two orthogonal orientations. Our devices are composed of two back-to-back p-n junctions formed by stacking anisotropic light-emitting materials, black phosphorus and black arsenic-phosphorus with MoS2. By controlling the crystallographic orientations and engineering the band profile of heterostructures, the emissions of two junctions exhibit distinct spectral ranges and polarization directions; more importantly, these two electroluminescence (EL) units can be independently activated, depending on the polarity of the applied bias. Furthermore, we show that when operating our emitter under the polarity-switched pulse mode, the time-averaged EL exhibits the characteristics of broad spectral coverage, encompassing the entire first mid-IR atmospheric window (λ: 3-5 µm), and electrically tunable spectral shapes.

Localization-enhanced moiré exciton in twisted transition metal dichalcogenide heterotrilayer superlattices.

The stacking of twisted two-dimensional (2D) layered materials has led to the creation of moiré superlattices, which have become a new platform for the study of quantum optics. The strong coupling of moiré superlattices can result in flat minibands that boost electronic interactions and generate interesting strongly correlated states, including unconventional superconductivity, Mott insulating states, and moiré excitons. However, the impact of adjusting and localizing moiré excitons in Van der Waals heterostructures has yet to be explored experimentally. Here, we present experimental evidence of the localization-enhanced moiré excitons in the twisted WSe2/WS2/WSe2 heterotrilayer with type-II band alignments. At low temperatures, we observed multiple excitons splitting in the twisted WSe2/WS2/WSe2 heterotrilayer, which is manifested as multiple sharp emission lines, in stark contrast to the moiré excitonic behavior of the twisted WSe2/WS2 heterobilayer (which has a linewidth 4 times wider). This is due to the enhancement of the two moiré potentials in the twisted heterotrilayer, enabling highly localized moiré excitons at the interface. The confinement effect of moiré potential on moiré excitons is further demonstrated by changes in temperature, laser power, and valley polarization. Our findings offer a new approach for localizing moiré excitons in twist-angle heterostructures, which has the potential for the development of coherent quantum light emitters.

Prediabetes and all-cause mortality in young patients undergoing coronary artery angiography: a multicenter cohort study in China.

BACKGROUND: The prevalence of prediabetes is increasing in young adults and patients undergoing coronary angiography. However, whether prediabetes is a considerable risk factor for all-cause mortality remains undetermined in young patients undergoing coronary angiography. METHODS: In this study, we retrospectively included 8868 young patients (men aged < 45 years, women aged < 55 years) who underwent coronary angiography (CAG). Patients were categorized as normoglycemic, prediabetes and diabetes according to the HbA1c level or documented history of diabetes. The association of all-cause mortality with diabetes and prediabetes was detected by Cox proportional hazards regression analysis. RESULTS: A total of 3240 (36.5%) among 8868 young patients receiving CAG were prediabetes and 2218 (25.0%) were diabetes. 728 patients died during a median follow-up of 4.92 years. Compared to the normoglycemic group, prediabetes increased the risk of all-cause mortality in young CAG patients by 24%(adjusted HR: 1.24, 95% CI: 1.04-1.49, p = 0.019) and diabetes increased the risk of all-cause mortality by 46%(adjusted HR:1.46, 95% CI:1.2-1.79, p < 0.001). Subgroup analysis showed that diabetes and prediabetes increased the risk of death mainly in patients without comorbidities. CONCLUSION: Prediabetes accounts for more than one-third of the young adults undergoing CAG and was associated with an increased risk of all-cause mortality, active prevention strategy should be considered for these patients.