Realveolarization with inhalable mucus-penetrating lipid nanoparticles for the treatment of pulmonary fibrosis in mice.

The stemness loss-associated dysregeneration of impaired alveolar type 2 epithelial (AT2) cells abolishes the reversible therapy of idiopathic pulmonary fibrosis (IPF). We here report an inhalable mucus-penetrating lipid nanoparticle (LNP) for codelivering dual mRNAs, promoting realveolarization via restoring AT2 stemness for IPF treatment. Inhalable LNPs were first formulated with dipalmitoylphosphatidylcholine and our in-house-made ionizable lipids for high-efficiency pulmonary mucus penetration and codelivery of dual messenger RNAs (mRNAs), encoding cytochrome b5 reductase 3 and bone morphogenetic protein 4, respectively. After being inhaled in a bleomycin model, LNPs reverses the mitochondrial dysfunction through ameliorating nicotinamide adenine dinucleotide biosynthesis, which inhibits the accelerated senescence of AT2 cells. Concurrently, pathological epithelial remodeling and fibroblast activation induced by impaired AT2 cells are terminated, ultimately prompting alveolar regeneration. Our data demonstrated that the mRNA-LNP system exhibited high protein expression in lung epithelial cells, which markedly extricated the alveolar collapse and prolonged the survival of fibrosis mice, providing a clinically viable strategy against IPF.

Potential planting regions of Pterocarpus santalinus (Fabaceae) under current and future climate in China based on MaxEnt modeling.

This study modeled the habitat distribution of Pterocarpus santalinus, a valuable rosewood species, across China under current and future climate scenarios (SSPs126, SSPs245, and SSPs585) using MaxEnt. Our findings reveal that the current suitable habitat, spanning approximately 409,600 km2, is primarily located in the central and southern parts of Guangdong, Guangxi, Fujian, and Yunnan, as well as in the Hainan provinces, along with the coastal regions of Taiwan, and the Sichuan-Chongqing border. The habitat's distribution is significantly influenced by climatic factors such as temperature seasonality (bio4), mean temperature of the wettest quarter (bio8), annual mean temperature (bio1), and annual precipitation (bio12), while terrain and soil factors play a lesser role. Under future climate scenarios, the suitable habitat for P. santalinus is projected to expand, with a northeastward shift in its distribution center. This research not only sheds light on the geoecological characteristics and geographical distribution of P. santalinus in China but also offers a scientific basis for planning its cultivation areas and enhancing cultivation efficiency under changing climate conditions.

The Effect of Human Umbilical Cord Mesenchymal Stem Cell on Premature Ovarian Cell Senilism Through miR-10a.

Objective: To investigate the potential protective impact of miR-10a-modified HUMSCs-derived exosomes on both premature ovarian failure and the functionality of ovarian granulosa cells in a POF model. Methods: KGN cells were co-cultured with cisplatin-diaminedichloroplatinum (II) (10 µM) for 24 h to establish an in vitro POF model. The cells were distributed into three distinct groups: the control group, the POF group, and the POF + HUCMSC group. The plasmid sh-NC, sh-miR-10 a and miR-10 a mimic were transfected into KGN cells. After co-cultured with HUCMSC-EVs for 48 h, they were divided into HUCMSC group, sh-miR-10 a-HUMSCs-exosomes group and miR-10 a-HUMSCs-exosomes group. Flow cytometry was adopted to assess the impact of HUMSCs surface immune antigens and miR-10a-HUCMSCs-exosomes on KGN cell apoptosis. Additionally, the evaluation of cell proliferation was carried out through CCK-8 and EDU assays. Western blot analysis was utilized to detect the Caspase-3, Bax, and Bcl-2 proteins levels. Furthermore, the levels of TNF-α, IL-6, IL-10, MDA, SOD, and CAT were quantified using ELISA. Results: Compared with the Control group, the POF group inhibited the growth of ovarian granulosa cells (P<0.01), reduced the number of EDU cells (P<0.01), and increased the protein expression of Caspase-3 (P<0.05) and Bax (P<0.01). HUMSCs treatment significantly down-regulated the expression of IL-6, TNF-α and MDA, while up-regulating the expression of IL-10, SOD and CAT (P<0.01); the overexpression of miR-10a promoted cell growth, besides, the introduction of miR-10a-HUMSCs-derived exosomes led to an elevation in the proliferation rate of OGCs affected by POF and concurrently suppressed the apoptosis rate. Conclusion: HUMSCs-derived exosomes modified by miR-10a have protective effects on premature ovarian failure and ovarian granulosa cell function in POF model.

Delivery of nanosecond laser pulses by multi-mode anti-resonant hollow core fiber at 1†µm wavelength.

In this paper we explore the application of low-loss multimode anti-resonant hollow-core fiber (MM-AR-HCF) in the delivery of nanosecond laser pulses at 1 µm wavelength. MM-AR-HCF with large core offers a rich content of low-loss higher-order modes which plays a key role in the efficient coupling and transmission of high-power laser of low beam quality. In the experiment, laser pulses of an average pulse energy of 21.8 mJ with 14.6 ns pulse width (corresponding a peak power of 1.49 MW) are transmitted through MM-AR-HCF of 9.8 m length without damage. 85% transmission efficiency is achieved where the incident laser beam suffers a low beam quality with M2 x and M2 y of 2.18 and 1.99 respectively. Laser-induced damage threshold (LIDT) of MM-AR-HCF was measured to be 22.6 mJ for 85% transmission efficiency, which is 7 times higher than that for a multimode silica optical fiber with a large core of 200 µm.

Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

The cooperative migration dynamics of particles correlates to the nature of hexatic-isotropic phase transition in 2D systems of corner-rounded hexagons.

In the two-dimensional (2D) melting transition of colloidal systems, the hexatic-isotropic (H-I) transition can be either first-order or continuous. However, how particle dynamics differs at the single-particle level during these two different melting transitions remains to be disclosed. In this work, by Brownian dynamics (BD) simulations, we have systematically studied the dynamic behavior of corner-rounded hexagons during the H-I transition, for a range of corner-roundness ζ = 0.40 to 0.99 that covers the crossover from the continuous to first-order nature of H-I transition. The results show that hexagons with ζ ≤ 0.5 display a continuous H-I transition, whereas those with ζ ≥ 0.6 demonstrate a first-order H-I transition. Dynamic analysis shows different evolution pathways of the dominant cluster formed by migrating particles, which results in a droplet-like cluster structure for ζ = 0.40 hexagons and a tree-like cluster structure for ζ = 0.99 hexagons. Further investigations on the hopping activities of particles suggest a cooperative origin of migrating clusters. Our work provides a new aspect to understand the dependence of the nature of H-I transition on the roundness of hexagons through particle dynamic behavior.

Enhance Carrier Diffusion of Monolayer MoSe2 by Interface Engineering.

Two-dimensional materials hold great potentials for beyond-CMOS (complementary metal-oxide-semiconductor) electronical and optoelectrical applications, and the development of field effect transistors (FET) with excellent performance using such materials is of particular interest. How to improve the performance of devices thus becomes an urgent issue. The performance of FETs depends greatly on the intrinsic electrical properties of the channel materials, meanwhile the device interface quality, such as extrinsic scattering of charged impurities, charge traps, and substrate surface roughness have a great influence on the performance. In this paper, the impact of the interface quality on the carrier diffusion behaviors of monolayer (ML) MoSe2 has been investigated by using an in situ ultrafast laser technique to avoid the surface contamination during device fabrication process. Two types of self-assembled monolayers (SAMs) are introduced to modify the gate dielectric surface through an interface engineering approach to obtain chemical-stable interfaces. The results showed that the transport properties of ML MoSe2 were enhanced after interface engineering, for example, the carrier mobility of ML MoSe2 was improved from ∼59.4 to ∼166.5 cm2 V-1 s-1 after the SAM modification. Meanwhile, the photocarrier dynamics of ML MoSe2 before and after interfacial engineering were also carefully studied. Our studies provide a feasible method for improving the carrier diffusion behaviors of such materials, and making them suited for application in future integrated circuit.

PD-L1 expression in ovarian clear cell carcinoma using the 22C3 pharmDx assay.

BACKGROUND: Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti-PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC. METHODS AND RESULTS: The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion. CONCLUSIONS: In conclusion, anti-PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.

COVID-19 and retinal layer thickness: A bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have reported that COVID-19 is associated with alterations in retinal layer thickness, including changes in the ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL). However, the causal relationships remain unknown. Therefore, we assessed the direction and strength of the causal relationship between COVID-19 and GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian randomization (MR) design. METHODS: Data were obtained from a large-scale COVID-19 Host Genetics Initiative (Nsample = 6,512,887), GCIPL dataset (Ncase = 31,434), and RNFL dataset (Ncase = 31,434). The inverse-variance weighted (IVW) method is the primary approach used to estimate causal effects. MR Egger, weighted median, weighted mode, MR Egger (bootstrap), and penalized weighted median methods were applied. Sensitivity analyses were implemented with RadialMR, MRPRESSO, MR-Egger regression, Cochran's Q statistic, leave-one-out analysis, and the funnel plot. RESULTS: Forward MR analysis revealed that genetically identified COVID-19 susceptibility significantly increased the risk of GCIPL thickness (OR = 2.428, 95 % confidence interval [CI]:1.493-3.947, PIVW = 3.579 × 10-4) and RNFL thickness (OR = 1.735, 95 % CI:1.198-2.513, PIVW = 3.580 × 10-3) after Bonferroni correction. Reverse MR analysis did not indicate a significant causal association between GCIPL and RNFL thicknesses and COVID-19 phenotypes. No significant horizontal pleiotropy was found in the sensitivity analysis. CONCLUSIONS: The host genetic liability to COVID-19 susceptibility was causally associated with increased GCIPL and RNFL thicknesses. Documenting this association increases our understanding of the pathophysiological mechanisms underlying COVID -19 susceptibility in retinopathy.

Research Progress of Single-Photon Emitters Based on Two-Dimensional Materials.

From quantum communications to quantum computing, single-photon emitters (SPEs) are essential components of numerous quantum technologies. Two-dimensional (2D) materials have especially been found to be highly attractive for the research into nanoscale light-matter interactions. In particular, localized photonic states at their surfaces have attracted great attention due to their enormous potential applications in quantum optics. Recently, SPEs have been achieved in various 2D materials, while the challenges still remain. This paper reviews the recent research progress on these SPEs based on various 2D materials, such as transition metal dichalcogenides (TMDs), hexagonal boron nitride (hBN), and twisted-angle 2D materials. Additionally, we summarized the strategies to create, position, enhance, and tune the emission wavelength of these emitters by introducing external fields into these 2D system. For example, pronounced enhancement of the SPEs' properties can be achieved by coupling with external fields, such as the plasmonic field, and by locating in optical microcavities. Finally, this paper also discusses current challenges and offers perspectives that could further stimulate scientific research in this field. These emitters, due to their unique physical properties and integration potential, are highly appealing for applications in quantum information and communication, as well as other physical and technological fields.

Radiomic Prediction of CCND1 Expression Levels and Prognosis in Low-grade Glioma Based on Magnetic Resonance Imaging.

OJECTIVES: Low-grade glioma (LGG) is associated with increased mortality owing to recrudescence and the tendency for malignant transformation. Therefore, it is imperative to discover novel prognostic biomarkers as existing traditional prognostic biomarkers of glioma, including clinicopathological features and imaging examinations, are unable to meet the clinical demand for precision medicine. Accordingly, we aimed to evaluate the prognostic value of cyclin D1 (CCND1) expression levels and construct radiomic models to predict these levels in patients with LGG MATERIALS AND METHODS: A total of 412 LGG cases from The Cancer Genome Atlas (TCGA) were used for gene-based prognostic analysis. Using magnetic resonance imaging (MRI) images stored in The Cancer Imaging Archive with genomic data from TCGA, 149 cases were selected for radiomics feature extraction and model construction. After feature extraction, the radiomic signature was constructed using logistic regression (LR) and support vector machine (SVM) analyses. RESULTS: CCND1 was identified as a prognosis-related gene with differential expression in tumor and normal samples and plays a role in regulating both the cell cycle and immune response. Landmark analysis revealed that high-expression levels of CCND1 were beneficial for survival (P < 0.05) in advanced LGG. Four optimal radiomics features were selected to construct radiomics models. The performance of LR and SVM achieved areas under the curve of 0.703 and 0.705, as well as 0.724 and 0.726 in the training and validation sets, respectively. CONCLUSION: Elevated levels of CCND1 expression could impact the prognosis of patients with LGG. MRI-based radiomics, especially the AUC values, can serve as a novel tool for predicting CCND1 expression and understanding the correlation between elevated CCND1 expression and prognosis. AVAILABILITY OF DATA AND MATERIALS: The datasets analyzed during the current study are available in the TCGA, TCIA, UCSC XENA and GTEx repository, https://portal.gdc.cancer.gov/, https://www.cancerimagingarchive.net/, https://xenabrowser.net/datapages/, https://www.gtexportal.org/home/.

Convergent Neuroimaging and Molecular Signatures in Mild Cognitive Impairment and Alzheimer's Disease: A Data-Driven Meta-Analysis with N = 3,118.

The current study aimed to evaluate the susceptibility to regional brain atrophy and its biological mechanism in Alzheimer's disease (AD). We conducted data-driven meta-analyses to combine 3,118 structural magnetic resonance images from three datasets to obtain robust atrophy patterns. Then we introduced a set of radiogenomic analyses to investigate the biological basis of the atrophy patterns in AD. Our results showed that the hippocampus and amygdala exhibit the most severe atrophy, followed by the temporal, frontal, and occipital lobes in mild cognitive impairment (MCI) and AD. The extent of atrophy in MCI was less severe than that in AD. A series of biological processes related to the glutamate signaling pathway, cellular stress response, and synapse structure and function were investigated through gene set enrichment analysis. Our study contributes to understanding the manifestations of atrophy and a deeper understanding of the pathophysiological processes that contribute to atrophy, providing new insight for further clinical research on AD.

Highly Efficient Acidic Electrosynthesis of Hydrogen Peroxide at Industrial-Level Current Densities Promoted by Alkali Metal Cations.

Acidic H2O2 synthesis through electrocatalytic 2e- oxygen reduction presents a sustainable alternative to the energy-intensive anthraquinone oxidation technology. Nevertheless, acidic H2O2 electrosynthesis suffers from low H2O2 Faradaic efficiencies primarily due to the competing reactions of 4e- oxygen reduction to H2O and hydrogen evolution in environments with high H+ concentrations. Here, we demonstrate the significant effect of alkali metal cations, acting as competing ions with H+, in promoting acidic H2O2 electrosynthesis at industrial-level currents, resulting in an effective current densities of 50-421 mA cm-2 with 84-100 % Faradaic efficiency and a production rate of 856-7842 µmol cm-2 h-1 that far exceeds the performance observed in pure acidic electrolytes or low-current electrolysis. Finite-element simulations indicate that high interfacial pH near the electrode surface formed at high currents is crucial for activating the promotional effect of K+. In situ attenuated total reflection Fourier transform infrared spectroscopy and ab initio molecular dynamics simulations reveal the central role of alkali metal cations in stabilizing the key *OOH intermediate to suppress 4e- oxygen reduction through interacting with coordinated H2O.

Acupuncture for poststroke coma: A systematic review and meta-analysis.

BACKGROUND: Despite being widely applied in clinical practice, the wake-promoting effect of acupuncture in poststroke coma patients remains controversial. OBJECTIVE: This study aimed to evaluate the efficacy of acupuncture for the treatment of poststroke coma. METHODS: Randomized controlled trials (RCTs) of acupuncture for treating poststroke coma were identified in PubMed, Cochrane Library, EMBASE, CNKI, WanFang and VIP up to 25 November 2023. The main outcomes were Glasgow Coma Scale (GCS) score, National Institute of Health Stroke Scale (NIHSS) score, awakening ratio and clinically effective ratio. Stata 17 and Review Manager 5.4 software were used for mate analysis. RESULTS: A total of 34 RCTs involving 2757 patients were included. GCS (WMD = 1.78; 95% CI: 1.35 to 2.21) and NIHSS score (WMD = -2.84; 95% CI: -3.84 to -1.84) were significantly increased in acupuncture group compared with control group. Acupuncture combined with routine treatment may be better than routine treatment in improving the awakening ratio (RR= 1.65; 95% CI: 1.24 to 2.91) and the clinically effective ratio (RR= 1.20; 95% CI: 1.13 to 1.27). Some methodological flaws were identified in the included studies, including non-implementation of blinding, inappropriate disease assessment and heterogeneous interventions. CONCLUSIONS: The existing evidence suggests that acupuncture combined with conventional treatment may be an effective treatment for poststroke coma patients. In the meantime, more high-quality RCTs are needed to demonstrate these findings due to methodological weaknesses like randomization, blinding, heterogeneous interventions and long-term follow-up.

Life disturbance and hospital visit experiences among Chinese patients with benign prostatic hyperplasia: a qualitative study.

BACKGROUND: The impact of lower urinary tract symptoms (LUTS) on the quality of life of patients with benign prostatic hyperplasia (BPH) has been rarely reported. Additionally, the challenges faced by these patients in seeking medical care have often been overlooked. In order to explore the personal struggles caused by LUTS and the difficulties or barriers experienced by Chinese patients with BPH when seeking help, we conducted a qualitative interview study. METHODS: Qualitative interviews were conducted among 46 patients with BPH who were hospitalized in three tertiary hospitals in China from July 2021 to November 2022. Grounded theory was adopted as the methodology for the qualitative study. After obtaining written informed consent from the study participants, semi-structured interviews were conducted according to the question guidelines. The interview process was audio-recorded; subsequently, the recordings were transcribed, coded, and thematically analyzed. RESULTS: The difficulties faced by Chinese patients with BPH were classified into seven main themes: (i) disturbed life, (ii) mental burden, (iii) disease cognition and communication, (iv) delayed treatment, (v) medication status, (vi) hospital visits barriers, and (vii) medical insurance issues. Further, each theme was subdivided into 2-5 sub-themes. CONCLUSIONS: LUTS have a certain effect on the life and spirit of patients with BPH. These patients face different degrees of difficulties in treatment and hospital visits. Therefore, better healthcare systems and additional social support are crucial for improving the current plight of these patients.

Photocatalyzed C3-H Nitrosylation of Imidazo[1,2-a]pyridine under Continuous Flow and External Photocatalyst-, Oxidant-, and Additive-Free Conditions.

This study reports a protocol for the highly regioselective photocatalyzed C-H nitrosylation of imidazo[1,2-a]pyridine scaffolds at the C3 position under a combination of visible-light irradiation and continuous flow without any external photocatalyst. This protocol involves mild and safe conditions and shows good tolerance to air and water along with excellent functional group compatibility and site selectivity, generating various 3-nitrosoimidazo[1,2-a]pyridines in excellent yields under photocatalyst-, oxidant-, and additive-free conditions.Notably, the proposed nitrosylation reaction, which introduces the chromophore NO into imidazo[1,2-a]pyridine scaffolds, occurs efficiently under visible-light irradiation without any additional photocatalyst owing to the intense light-absorption characteristics of the nitrosylation products. This study could guide future studies on the development of green organic-synthesis strategies with a wide variety of potential applications.

Transcriptomic and neuroimaging data integration enhances machine learning classification of schizophrenia.

Background: Schizophrenia is a polygenic disorder associated with changes in brain structure and function. Integrating macroscale brain features with microscale genetic data may provide a more complete overview of the disease etiology and may serve as potential diagnostic markers for schizophrenia. Objective: We aim to systematically evaluate the impact of multi-scale neuroimaging and transcriptomic data fusion in schizophrenia classification models. Methods: We collected brain imaging data and blood RNA sequencing data from 43 patients with schizophrenia and 60 age- and gender-matched healthy controls, and we extracted multi-omics features of macroscale brain morphology, brain structural and functional connectivity, and gene transcription of schizophrenia risk genes. Multi-scale data fusion was performed using a machine learning integration framework, together with several conventional machine learning methods and neural networks for patient classification. Results: We found that multi-omics data fusion in conventional machine learning models achieved the highest accuracy (AUC ~0.76-0.92) in contrast to the single-modality models, with AUC improvements of 8.88 to 22.64%. Similar findings were observed for the neural network, showing an increase of 16.57% for the multimodal classification model (accuracy 71.43%) compared to the single-modal average. In addition, we identified several brain regions in the left posterior cingulate and right frontal pole that made a major contribution to disease classification. Conclusion: We provide empirical evidence for the increased accuracy achieved by imaging genetic data integration in schizophrenia classification. Multi-scale data fusion holds promise for enhancing diagnostic precision, facilitating early detection and personalizing treatment regimens in schizophrenia.