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Abstract This research work focuses on addressing the challenges of electric load forecasting through the combination of Support Vector Regression and Long Short-Term Memory (SVR/LSTM) methodology. The model has been modified by a flexible version of the Gorilla Troops optimization algorithm. The objective of this study is to enhance the precision and effectiveness of load forecasting models by integrating the adaptive functionalities of the Gorilla Troops algorithm within the SVR/LSTM framework. To assess the efficacy of the proposed methodology, a comprehensive series of experiments and evaluations have been undertaken, utilizing authentic data obtained from 200 residential properties located in Texas, United States of America. The dataset comprises historical records of electricity consumption, meteorological data, and other pertinent variables that exert an impact on energy demand. The presence of this general dataset enhances the dependability and inclusiveness of the empirical findings. The proposed methodology was evaluated against various contemporary load forecasting techniques that are widely employed in the industry. The results of a comprehensive evaluation and performance analysis indicate that the modified SVR/LSTM model exhibits superior performance compared to the existing methods in terms of accuracy and robustness. The comparison results unequivocally demonstrate the superiority of the proposed method in accurately forecasting electric load demand.

Abstract Background Sublobar resection (wedge resection and segmentectomy) has been established as an oncologically equivalent option to lobectomy for early‐stage patients with non‐small cell lung cancer (NSCLC) ≤ 2 cm. However, the optimal approach of sublobar resection remains subject to debate. In the present study we aimed to compare the oncological outcomes of wedge resection and segmentectomy in these patients. Methods We identified patients with pT1a‐bN0M0 NSCLC who underwent wedge resection and segmentectomy from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A Cox regression model and propensity‐score matching (PSM) analysis were used. Overall survival (OS) and lung cancer‐specific survival (LCSS) were compared using the Kaplan–Meier method. Results A total of 4190 patients met our selection criteria, including wedge resection in 3137 and segmentectomy in 1053. Patients undergoing wedge resection were less likely to have total lymph nodes resected (4 vs. 7, p

Musk deer (Moschus spp.) are widely known for its musk and are globally endangered as a result of poaching, habitat loss, and fragmentation. To facilitate restoration of the alpine musk deer (M. chrysogaster) in existing areas, reliable estimates of population size and influencing factors are essential to assess effectiveness of conservation interventions, particularly for isolated musk deer populations in patches. In this paper, we used line transect and camera trap data collected from 2020 to 2022 in the Helan mountains to assess the population status and characterized the influencing factors of alpine musk deer. Our findings indicate that musk deer are patchily distributed in three areas of high elevation, with the population limited to less than 200 individuals, remaining below historic levels (compared to 1995). There was a significant positive correlation between the role of sympatric species on musk deer, with red fox (Vulpes vulpes), badger (Meles meles) and blue eared-pheasant (Crossoptilon auritum) having a significant effect on the out-modeled pathway. Variable but insignificant effects of anthropogenic activities were observed across all species categories, which could be due to mutual adaptation over time. Our results imply that the recovery of sensitive population in island-like habitats remains challenging and may be exacerbated by limited environment and resources. Our study underscores the necessity of establishing ecological corridors to enhance habitat connectivity for alpine musk deer, undertaking conservation genetics research on isolated populations, controlling stray dogs to maintain interspecific balance, and implementing electronic fencing to mitigate human disturbance and resource competition. This study provides basic information for understanding the population status of alpine musk deer and offers insights for conservation efforts.

Cancer stem cells (CSCs) play a crucial role in tumor initiation, recurrence, metastasis, and drug resistance. However, the current understanding of CSCs in hepatocellular carcinoma (HCC) remains incomplete. Through a comprehensive analysis of the database, it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a critical enzyme involved in cholesterol synthesis, is up-regulated in HCC tissues and liver CSCs. Moreover, high expression of HMGCR is associated with a poor prognosis in patients with HCC. Functionally, HMGCR promotes the stemness and metastasis of HCC both in vitro and in vivo. By screening various signaling pathway inhibitors, we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in HCC. Mechanistically, HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger 1. Inhibition of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in HCC. Notably, simvastatin, an FDA-approved cholesterol-lowering drug, has been shown to inhibit stemness and metastasis of HCC by targeting HMGCR. Taken together, our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling, and simvastatin holds the potential for clinical suppression of HCC metastasis.

Abstract This study investigates the adaptive strategies of the Alashan Ground Squirrel (Spermophilus alashanicus) in response to habitat changes, as rodents are sensitive indicators of ecosystem changes. Despite its ecological importance, the genome and microbiome of this species have not been thoroughly studied. This research fills this gap by presenting the first comprehensive metagenomic and transcriptomic datasets of the species. Transcriptomic data was collected from five tissue types, including heart, liver, cecum, muscle, and blood, resulting in the assembly of 72,156 unigenes. Metagenomic sequencing identified predominant bacterial groups such as Firmicutes, Bacteroidetes, Verrucomicrobia, Urovircota, and Proteobacteria. Our workflow involved RNA and DNA extraction, library preparation, assembly, and annotation, yielding valuable insights into gene discovery, microbial composition, and further genome and microbial function studies. In conclusion, our findings have significant implications for understanding the adaptive mechanisms of this species in response to environmental changes.

Abstract Background The surgical outcomes for younger patients with non‐small cell lung cancer (NSCLC) remain uncertain. The aim of this study was to investigate the clinical features long‐term survival outcomes in younger individuals with NSCLC following surgery. Methods We queried the Surveillance, Epidemiology, and End Results database from 2010 to 2017, selecting all pathologically confirmed NSCLC cases that underwent cancer‐directed surgery. Younger patients were defined as those aged 18–50 years, while older patients were 51–80 years. Propensity score matching (PSM) was implemented to mitigate selection bias. Overall survival (OS) and lung cancer‐specific survival (LCSS) were compared using the Kaplan–Meier method. Results Among the 33 586 treated surgically patients, 2223 (6.6%) were young. Compared to the older group, younger patients had a higher frequency of female gender, non‐white ethnicity, carcinoid tumors, stage IV disease, pneumonectomy, and postoperative adjuvant therapies. The 5‐year OS rates were significantly higher for younger patients (79.3% vs. 62.0%; p

Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice, significantly enhancing the effects of the combination. Our study revealed DOX was an ICD inducer, stimulating immune responses and promoting maturation of dendritic cells (DCs). Additionally, QUE served as a TME regulator by inhibiting the cyclooxygenase-2 (COX2)-prostaglandin E2 (PGE2) axis, which influenced various immune cells, including increasing cytotoxic T cells (CLTs) infiltration, promoting M1 macrophage polarization, and reducing regulatory T cells (Tregs) infiltration. The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment. This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

Abstract As an alternative to antibiotics in response to antimicrobial-resistant infections, bacteriophages (phages) are garnering renewed interest in recent years. However, the massive preparation of phage is restricted using traditional pathogens as host cells, which incurs additional costs and contamination. In this study, an opportunistic pathogen, Klebsiella pneumoniae used to convert glycerol to 1,3-propanediol (1,3-PDO), was reused to prepare phage after fermentation. The phage infection showed that the fed-batch fermentation broth containing 71.6 g/L 1,3-PDO can be directly used for preparation of phage with a titer of 1 × 108 pfu/mL. Then, the two-step salting-out extraction was adopted to remove most impurities, e.g. acetic acid (93.5%), ethanol (91.5%) and cells (99.4%) at the first step, and obtain 1,3-PDO (56.6%) in the top phase as well as phage (97.4%) in the middle phase at the second step. This integrated process provides a cheap and environment-friendly manner for coproduction of 1,3-PDO and phage. Graphical abstract

Osteosarcoma is usually resistant to immunotherapy and, thus primarily relies on surgical resection and high-dosage chemotherapy. Unfortunately, less invasive or toxic therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) generally failed to show satisfactory outcomes. Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma. Herein, a simple nanocomposite that synergistically combines CDT, PTT, and chemotherapy for osteosarcoma treatment was fabricated. In this composite, small 2D NiFe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil (5-FU) with high loading capacity. The nanospheres were then adsorbed onto larger 2D Ti3C2 MXene monolayers and finally shielded by bovine serum albumin (BSA) to form 5-FU@NiFe-LDH/Ti3C2/BSA nanoplatforms (5NiTiB). Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy, NiFe-LDH driven chemodynamic effects, and MXene-based photothermal killing collectively exhibited a synergistic “all-in-one” anti-tumor effect. 5NiTiB improved tumor suppression rate from

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program. Phosphoenolpyruvate carboxylase 1 (PCK1), a gluconeogenic metabolic enzyme, is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis. The oncogenesis and progression of tumors are closely related to cancer stem cells. It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma. Herein, the results showed that PCK1 inhibited the self-renewal property of hepatoma cells, reduced the mRNA level of cancer stem cell markers, and inhibited tumorigenesis. Moreover, PCK1 increased the sensitivity of hepatocellular carcinoma cells to sorafenib. Furthermore, we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation. Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib. Thus, combined treatment with verteporfin and sorafenib may be a potential anti-tumor strategy in hepatocellular carcinoma.

Abstract Developing efficient and economical electrocatalysts for acidic oxygen evolution reaction (OER) is essential for proton exchange membrane water electrolyzers (PEMWE). Cobalt oxides are considered promising non-precious OER catalysts due to their high activities. However, the severe dissolution of Co atoms in acid media leads to the collapse of crystal structure, which impedes their application in PEMWE. Here, we report that introducing acid-resistant Ir single atoms into the lattice of spinel cobalt oxides can significantly suppress the Co dissolution and keep them highly stable during the acidic OER process. Combining theoretical and experimental studies, we reveal that the stabilizing effect induced by Ir heteroatoms exhibits a strong dependence on the distance of adjacent Ir single atoms, where the OER stability of cobalt oxides continuously improves with decreasing the distance. When the distance reduces to about 0.6 nm, the spinel cobalt oxides present no obvious degradation over a 60-h stability test for acidic OER, suggesting potential for practical applications.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

AbstractThe Alashan ground squirrel (Spermophilus alashanicus) is primarily distributed in the regions of Inner Mongolia and Ningxia, China. In this study, we present the first complete mitochondrial genome of S. alashanicus. The genome spans 16,464 base pairs and comprises 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a single control region with a marked AT bias. The overall GC content is 35.4%. Phylogenetic analyses indicate that S. alashanicus clusters are closely associated with S. dauricus. This comprehensive characterization of the S. alashanicus mitochondrial genome serves as a foundational resource for future studies on mitochondrial evolution, species identification, population genomics, and phylogenetics.

Abstract The metal-support interactions (MSI) could greatly determine the electronic properties of single-atom catalysts, thus affecting the catalytic performance. However, the typical approach to regulating MSI usually suffers from interference of the variation of supports or sacrificing the stability of catalysts. Here, we effectively regulate the site-specific MSI of Ir single atoms anchored on Ni layered double hydroxide through an electrochemical deposition strategy. Cathodic deposition drives Ir atoms to locate at three-fold facial center cubic hollow sites with strong MSI, while anodic deposition drives Ir atoms to deposit onto oxygen vacancy sites with weak MSI. The mass activity and intrinsic activity of Ir single-atom catalysts with strong MSI towards oxygen evolution reaction are 19.5 and 5.2 times that with weak MSI, respectively. Mechanism study reveals that the strong MSI between Ir atoms and the support stimulates the activity of Ir sites by inducing the switch of active sites from Ni sites to Ir sites and optimizes the adsorption strength of intermediates, thereby enhancing the activity.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

There is a need to reduce human–wildlife conflicts in the area around Liupanshan Nature Reserve in Ningxia Hui Autonomous Region, China. This study investigated the financial losses caused by wild boar and their causes. A questionnaire investigation (n = 135) and a field test were conducted, which included 108 sample lines and 97 infrared cameras. A principal component analysis and generalised linear model was used to analyse the importance of the effect of the factors on wild boar damage. Based on an estimate of 17,049 wild boars in the study area, we found that in the agricultural land owned by the residents, the boar density of each county and distance from the village to the nature reserve were the most significant factors that affected crop damage. Then, financial losses in spring, summer, and autumn had a moderate effect on financial loss, and the crop type had the lowest effect. We recommend reducing the wild boar population by increasing leisure hunting and the number of leopards. Additionally, a focus on farmland protection is a practical way to prevent wild boar invasions. Meanwhile, it is also necessary to conduct long-term monitoring of wild boar population status and manage the relationship between the government, research teams, and local people to more efficiently and comprehensively reduce conflicts between humans and wild boars.

This study conducted a comparative analysis of extractable hopanoid hydrocarbons and those released via stepwise pyrolysis of typical Eocene immature oil shales in China, namely the Huadian, Maoming, and Fushun shales. Both the Huadian and Maoming shales exhibit immature indicators in extractable and kerogen-bound hopanoids (notably, high abundance of C29 to C32 17β,21β-hopanes and unsaturated hopenes). In contrast, the Fushun oil shale's hopanoids from extracts and pyrolyzates suggest a higher maturity level. The absence of neohopenes in the pyrolyzates of the shales underpins that the kerogen-bound hopanoid skeletons resist rearrangement. However, the Huadian oil shale's asymmetric distribution of C29 and C30 hopenes and neohopenes hints at the presence of an additional source. Novel unsaturated hopenes, such as hop-20 (21)-enes, identified in pyrolyzates of the three kerogens at various pyrolysis temperatures, reveal the occurrence of double bonds in kerogen-bound hopanoid skeletons without methyl rearrangements. The absence of hop-20-(21)-ene in extracts suggests that it might act as an intermediate of these novel hopenes during the epimerization of hopanoid skeletons within kerogen. The extractable and pyrolytic hopanoids' stereochemical alignment indicates that epimerization may occur in both ring systems and alkyl side chains of kerogen-bound hopanoid skeletons. Sequential stepwise pyrolysis proves to be a quick screening method for geological hopanoids without causing any significant alteration to the original skeletons even when cracking multiple covalent bonds is necessary.

As one of the major fractions of petroleum and/or source rock extracts, asphaltene is commonly characte-rized by complicate molecular structures as well as relatively higher molecular weight (MW). The asphaltene occluded biomarkers have been well introduced to be valuable for geochemical research whilst the actual molecular weight and molecular structures of asphaltene macromolecules studies show value in petroleum exploration and production, laboratory treatments as well as petroleum chemical storage and transportation etc. The structure, molecular weight and related experimental measurement methods of asphaltenes reported in this paper are reviewed, in an attempt to provide a more comprehensive understanding on the molecular structure, molecular weight and physicochemical properties of asphaltenes, so as to provide basic data for applying asphaltene geochemical research in the exploration and development study of conventional and unconventional reservoirs. In view of the different views on the structure and molecular weight of asphaltene molecules, the results are reviewed, the main reasons for the controversy are discussed based on the current status of experimental measurement technology, and the future development trend of related researches is pointed out. The current understanding of the structure of asphaltene macromolecules is mainly based on two completely different models, i.e., the island model and archipelago model. The former suggests that asphaltenes have a single aromatic nucleus and the molecular weight characterized is relatively lower. The latter believes that asphaltenes have multiple aromatic nuclei and the molecular weight characterized is relatively higher. The above two models of asphaltene molecular structure are supported by their own experimental measurement results, among which the evidences of the "island" model mainly come from fluorescence spectroscopy, laser vaporization/laser ionization mass spectrometry (L2MS) analysis and stem from various ionization high-resolution (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR-MS) analysis technologies. The evidences for the archipelago model mainly come from gas phase permeation measurement, size exclusion chromatography and chemical degradation.

Wildlife activity patterns, which reveal the daily allocation of time and energy, are crucial for understanding survival pressures, adaptive strategies, and behavioral characteristics in different environments. Among ungulates, grouping behavior is a prevalent adaptive trait that reflects the population structure, mating systems, and life history strategies formed over long-term evolutionary processes. This study aimed to elucidate the daily activity patterns and grouping characteristics of the rare goitered gazelle (Gazella subgutturosa) in the Helan Mountains of western China from 2022 to 2023 using camera trap monitoring. With a total of 3869 camera days of effective trapping, we recorded 442 independent detections of goitered gazelles. The results revealed the following: (1) Goitered gazelle is primarily active during the day, showing an activity pattern similar to crepuscular animals, with two activity peaks occurring after dawn and before dusk. (2) Daily activity patterns showed both seasonal and sex differences. In the warm season, morning activity peaks occurred earlier, and afternoon peaks occurred later compared to the cold season. The overlap in daily activity patterns between females and males in the warm season was lower than that in the cold season, and this trend persisted throughout the year. (3) The number of times different types of groups were observed varied significantly, with single males and single females accounting for a larger proportion of all observed groups. There was no significant difference in group size across seasons, with groups typically consisting of 1–2 individuals. Our study provides detailed insights into the temporal ecology and population structure of goitered gazelles in arid and semi-arid ecosystems. This information will guide the identification of future conservation priorities and the development of management plans for the reserve.

Abstract Biological membranes often play important functional roles in biomimetic drug delivery systems. We discover that the circulation time and targeting capability of biological membrane coated nanovehicles can be significantly improved by reducing cholesterol level in the coating membrane. A proof-of-concept system using cholesterol-reduced and PD-1-overexpressed T cell membrane to deliver a photothermal agent and a STING agonist is thus fabricated. Comparing with normal membrane, this engineered membrane increases tumor accumulation by ~2-fold. In a melanoma model in male mice, tumors are eliminated with no recurrence in >80% mice after intravenous injection and laser irradiation; while in a colon cancer model in male mice, ~40% mice are cured without laser irradiation. Data suggest that the engineered membranes escape immune surveillance to avoid blood clearance while keeping functional surface molecules exposed. In summary, we develop a simple, effective, safe and widely-applicable biological membrane modification strategy. This “subtractive” strategy displays some advantages and is worth further development.

Abstract Rheumatoid arthritis (RA) is a common chronic inflammatory disorder that usually affects joints. It was found that roburic acid (RBA), an ingredient from anti-RA herb Gentiana macrophylla Pall., displayed strong anti-inflammatory activity. However, its medical application is limited by its hydrophobicity, lack of targeting capability and unclear functional mechanism. Here, we constructed a pH responsive dual-target drug delivery system hitchhiking RBA (RBA-NPs) that targeted both CD44 and folate receptors, and investigated its pharmacological mechanism. In rat RA model, the nanocarriers effectively delivered RBA to inflammatory sites and significantly enhanced the therapeutic outcomes compared with free RBA, as well as strongly reducing inflammatory cytokine levels and promoting tissue repair. Following analysis revealed that M1 macrophages in the joints were reprogrammed to M2 phenotype by RBA. Since the balance of pro- and anti-inflammatory macrophages play important roles in maintaining immune homeostasis and preventing excessive inflammation in RA, this reprogramming is likely responsible for the anti-RA effect. Furthermore, we revealed that RBA-NPs drove M1-to-M2 phenotypic switch by down-regulating the glycolysis level via blocking ERK/HIF-1α/GLUT1 pathway. Thus, our work not only developed a targeting delivery system that remarkably improved the anti-RA efficiency of RBA, but also identified a potential molecular target to reversely reprogram macrophages though energy metabolism regulation.

Background: Whether minimally invasive esophagectomy (MIE) is superior to open esophagectomy (OE) in the treatment of esophageal squamous cell carcinoma (ESCC) is still uncertain. Therefore, this multicenter prospective study aimed to compare MIE with OE in postoperative parameters and long-term survival. Methods: All hospitalized patients with cT1b-3N0–1M0 thoracic ESCC treated by MIE or OE were enrolled from 19 selected centers from April 1, 2015 to December 31, 2018. The propensity score matching (PSM) was performed to minimize the selection bias. The basic clinicopathological characteristics and 3-year overall survival (OS) as well as disease-free survival (DFS) of two groups were compared by R version 3.6.2. Results: MIE were performed in 1,387 patients and OE in 335 patients. 335 cases in each group were finally matched by PSM, and no significant differences in the essential demographic characteristics were observed between the MIE and OE groups after PSM. Compared with OE, MIE had significantly less intraoperative bleeding, less total drainage volume, shorter postoperative hospital stay, and harvested significantly more lymph nodes (LNs) (all P < 0.001). There were no significant differences in the major postoperative complications and death rates between MIE and OE. The 3-year OS and DFS were 77.0% and 68.1% in the MIE group versus 69.3% and 60.9% in the OE group (OS: P = 0.03; DFS: P = 0.09), and the rates were 75.1% and 66.5% in the MIE group versus 66.9% and 58.6% in the OE group for stage cII patients (OS: P = 0.04, DFS: P = 0.09), respectively. Conclusions: Compared with OE, MIE is a safe and effective treatment approach with similar mortality and morbidity. It has the advantages in harvesting more LNs, improving postoperative recovery and survival of stage cII ESCC patients.

Few studies have delved into the effects of heatwaves on sleep duration loss among older adults. Our study examined correlations between heatwave exposure and sleep duration reductions in this demographic. Utilizing data of 7,240 older adults drawn from the China Health and Retirement Longitudinal Study (CHARLS) from 2015 to 2018, we assessed sleep duration differences between the baseline year (2015) and follow-up year (2018). Absolute reductions in sleep duration were defined as differences of ≥ 1, 1.5, or 2 h. Changes in sleep duration were categorized based on cut-offs of 5 and 8 h, including excessive decrease, moderate to short and persistent short sleep duration types. 12 heatwave definitions combining four thresholds (90th, 92.5th, 95th, and 97.5th percentiles of daily minimum temperature) and three durations (≥2, ≥3 and ≥ 4 days) were used. Heatwave exposure was determined by the difference in the number of 12 preceding months' heatwave days or events in 2015 and the number of 12 preceding months' heatwave days or events in 2018. The results showed that increased heatwave events (defined as ≥ P90th percentile & lasting three days) were associated with a higher likelihood of ≥ 1-hour sleep reduction and persistent short sleep duration. An increase in heatwave event (defined as ≥ P95th percentile & lasting three days) was linked to shifts from moderate to short sleep duration. For the association between an absolute reduction in sleep duration and heatwave exposure, while higher thresholds signified greater sleep reduction risks, the effect estimates of longer durations were not uniformly consistent. We observed that air pollution and green space modified the relationship between heatwaves and sleep duration. Females, urban residents, and individuals with chronic diseases were identified as vulnerable populations. This study found that increased heatwave exposure was associated with a higher risk of sleep duration loss in older adults.

Abstract Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.

Abstract miRNA and other forms of small RNAs are known to regulate many biological processes. Single-cell small RNA sequencing can be used to profile small RNAs of individual cells; however, limitations of efficiency and scale prevent its widespread application. Here, we developed parallel single-cell small RNA sequencing (PSCSR-seq), which can overcome the limitations of existing methods and enable high-throughput small RNA expression profiling of individual cells. Analysis of PSCSR-seq data indicated that diverse cell types could be identified based on patterns of miRNA expression, and showed that miRNA content in nuclei is informative (for example, cell type marker miRNAs can be detected in isolated nuclei). PSCSR-seq is very sensitive: analysis of only 732 peripheral blood mononuclear cells (PBMCs) detected 774 miRNAs, whereas bulk small RNA analysis would require input RNA from approximately 106 cells to detect as many miRNAs. We identified 42 miRNAs as markers for PBMC subpopulations. Moreover, we analyzed the miRNA profiles of 9,533 cells from lung cancer biopsies, and by dissecting cell subpopulations, we identified potentially diagnostic and therapeutic miRNAs for lung cancers. Our study demonstrates that PSCSR-seq is highly sensitive and reproducible, thus making it an advanced tool for miRNA analysis in cancer and life science research.

Trollius, a genus in the Ranunculaceae family, has significant medicinal and ornamental value. It is widely distributed in China with 16 different species accepted. However, due to the lack of enough samples and information sites, the molecular phylogenetic relationships of Trollius have been unresolved till now. Here we sequenced, assembled and annotated the plastomes of 16 Trollius species to investigate their genomic characteristics, inverted repeat (IR) boundaries, sequence repeats, and hypervariable loci. In addition, the phylogenetic relationships of this genus was reconstructed based on the whole plastomes and the protein-coding sequences data-sets. The plastomes of Trollius ranged between 159,597 bp and 160,202 bp in length, and contained 113 unique genes, including 79 protein coding, 30 tRNA, and 4 rRNA. The IR boundaries were relatively conserved within the genus Trollius. 959 simple sequence repeats and 657 long sequence repeats were detected in the Trollius plastomes. We identified 12 highly polymorphic loci (Pi > 0.0115) that can be used as plastid markers in molecular identification and phylogenetic investigation of the genus. Besides, Trollius was a monophyletic group with the earliest divergence clade being Trollius lilacinus Bunge, and the remaining species were divided into two strongly-supported clades. The phylogeny in our study supported the traditional classification systems based on the color of sepal, but not the previous classification system based on the types and relative lengths of the nectaries, and distribution. The genomic resources provided in our study can be used in the taxonomy of the genus Trollius, promoting the development and utilization of this genus.

Three kerogen samples (JJZG-1, JJZG-2 and JJZG-3) isolated from the Permian Lucaogou shales of varying biodegradation levels (BLs ≈ 0, 3 and 7, respectively) were subjected to sequential stepwise pyrolysis combined with on-line detection of gas chromatography-mass spectrometry (GC-MS). Occluded fractions (bitumen II) released at low-temperature steps (≤410 °C) show consistent biodegradative signatures with that reported for solvent-extracted fractions (bitumen I) of the original shales, e.g., broad range of abundant n-alkanes, isoprenoids and regular hopanes for the non-biodegraded JJZG-1; trace n-alkanes and abundant hopanes for the moderately biodegraded JJZG-2; and no n-alkanes but still prominent hopanes including the microbially produced 25-nohopanes for the severely biodegraded JJZG-3. This consistency between bitumen II and bitumen I fractions indicates the biodegradability of the kerogen-occluded bitumen II with limited protection from host kerogen. A minor level of protection was suggested by the trace distribution of n-alkanes in the bitumen II of JJZG-2, whereas the bitumen I had no n-alkanes. The kerogen itself was more resistant to biodegradation as reflected by the persistence of high abundances of both n-alkanes and hopanes in the high temperature (≥460 °C) products of all three kerogen samples. However, the relative abundances of these product groups did show some evidence of biodegradation alteration, e.g., ratios of n-C15 alkene/C27 hop-17(21)-ene at 510 °C pyrolysis decreased by order of magnitude from the non-biodegraded (JJZG-1 = 27.4) to highly biodegraded (0.3 for JJZG-3) samples. The reduced biodegradation impact on the kerogen fraction (Cf. bitumen fractions) was also evident by the absence of 25-norhopanes in the high-temperature analysis of the JJZG-3 kerogen.

Global climate change, habitat fragmentation, and human interference have resulted in a significant, ongoing decline in the population of goitered gazelles. Effective conservation strategies require an understanding of resource requirements of threatened species, such as dietary needs. Therefore, we aimed to elucidate the food composition and seasonal dietary changes of goitered gazelles through microhistological analyses of fresh feces. Fabaceae (11.5%), Gramineae (9.4%), Chenopodiaceae (20.2%), Asteraceae (10.1%), and Rosaceae (19.5%) formed the primary dietary components of goitered gazelle. Additionally, Krascheninnikovia arborescens (13.4%) and Prunus sibirica (16.3%) were identified as the key forage plants. Forbs (50.4%) were the predominant plants for grazing throughout the year, particularly in the spring (72.9%). The proportion of trees in the diet was highest in the autumn (36.7%) and comparatively lower in other seasons. Furthermore, the proportions of shrubs (22.0%) and graminoids (14.8%) both reached their peaks in the winter. Our findings indicate that goitered gazelles strategically forage seasonally to cope with resource bottlenecks, enhancing their adaptability to arid and semi-arid habitats. Our study provides essential ecological information for the conservation of goitered gazelles and emphasizes the importance of dietary studies of species of ecological significance in environmentally sensitive areas.

The use of phase-sensitive optical time-domain reflectometry (Φ-OTDR)-distributed fiber vibration sensors to detect and identify damaged bags in bag dust collectors has the potential to overcome the inadequacy of traditional damaged bag detection methods. In our previous study, we verified the feasibility of applying this technique in the field of damaged bag detection in bag filters. However, many problems still occur in engineering applications when using this technology to detect and identify damaged filter bags in pulse-jet dust-cleaning bag dust collectors. Further studies are needed to characterize the fiber vibration signals inside different types of rectangular damaged filter bags. A filter bag damage identification and detection method based on empirical mode decomposition (EMD) and a backpropagation (BP) neural network is proposed. The signal feature differences between intact filter bags and damaged filter bags with different rectangular hole sizes and positions are comparatively analyzed, and optimal feature difference parameters are proposed. Support vector machine (SVM) and a BP neural network are used to recognize different types of filter bag signals, and the comparison results show that the BP neural network algorithm is better at recognizing different types of filter bags, obtaining the highest recognition rate of 97.3%.

Abstract Background Venous thromboembolism (VTE) is a common postoperative complication in general thoracic surgery, but the incidence of patients undergoing surgery for bronchiectasis was not known. The purpose of our study was to investigate the incidence of VTE in bronchiectasis patients undergoing lung resection and to evaluate the risk stratification effect of the modified caprini risk assessment model (RAM). Methods We prospectively enrolled patients with bronchiectasis who underwent lung resection surgery between July 2016 and July 2020.The postoperative duplex lower-extremity ultrasonography or(and) computed tomographic pulmonary angiography (CTPA) was performed to detect VTE. The clinical characteristics and caprini scores of VTE patients and non-VTE patients would be compared and analyzed. Univariate logistic regression was performed to evaluate whether higher Caprini scores were associated with postoperative VTE risk.In addition, We explored the optimal cutoff for caprini score in patients with bronchiectasis by using the receiver operating characteristic (ROC) curve. Results One hundred and seventeen patients were eligible based on the prospective study criteria. The postoperative VTE incidence was 8.5% (10/117). By comparing the clinical characteristics and Caprini scores of VTE and non-VTE patients, the median preoperative hospitalization (7 vs 5 days, P = 0.028) and Caprini score (6.5 vs 3,P < 0.001) were significantly higher in VTE patients. In univariate logistic regression, a higher Caprini score was associated with higher odds ratio (OR) for VTE of 1.7, 95% confidence interval (CI) was from 1.2 to 2.5 (P = 0.001), C-statistics was 0.815 in the modified caprini RAM for predicting VTE. In a multivariable analysis adjusting for preoperative hospitalization, a higher Caprini score was associated with higher odds OR for VTE of 1.8 (95%CI: 1.2–2.6, P = 0.002), C-statistics was 0.893 in the caprini RAM for predicting VTE. When taking the Caprini score as 5 points as the diagnostic threshold, the Youden index is the largest. Conclusions The postoperative VTE incidence in patients undergoing lung resection for bronchiectasis was 8.5%.The modified caprini RAM effectively stratified bronchiectasis surgery patients for risk of VTE and showed excellent predictive power for VTE. The patients with postoperative caprini scores = 5, should be recommended to take positive measures to prevent postoperative VTE. Trial Registration Chinese Clinical Trial Register: ChiCTR-EOC-17010577.

This study reports the occurrence of sustained and intensified microbial CH4 cycling in a giant lake in northwestern China during Early Permian climate warming. Lacustrine CH4 emissions may have contributed to the end of the Late Paleozoic Ice Age.

Abstract Background As a valuable medicinal plant, Rhodiola has a very long history of folk medicine used as an important adaptogen, tonic, and hemostatic. However, our knowledge of the chloroplast genome level of Rhodiola is limited. This drawback has limited studies on the identification, evolution, genetic diversity and other relevant studies on Rhodiola. Results Six Rhodiola complete chloroplast genomes were determined and compared to another Rhodiola cp genome at the genome scale. The results revealed a cp genome with a typical quadripartite and circular structure that ranged in size from 150,771 to 151,891 base pairs. High similarity of genome organization, gene number, gene order, and GC content were found among the chloroplast genomes of Rhodiola. 186 (R. wallichiana) to 200 (R. gelida) SSRs and 144 pairs of repeats were detected in the 6 Rhodiola cp genomes. Thirteen mutational hotspots for genome divergence were determined and could be used as candidate markers for phylogenetic analyses and Rhodiola species identification. The phylogenetic relationships inferred by members of Rhodiola cluster into two clades: dioecious and hermaphrodite. Our findings are helpful for understanding Rhodiola's taxonomic, phylogenetic, and evolutionary relationships. Conclusions Comparative analysis of chloroplast genomes of Rhodiola facilitates medicinal resource conservation, phylogenetic reconstruction and biogeographical research of Rhodiola.

Acute liver injury (ALI) has an elevated fatality rate due to untimely and ineffective treatment. Although, schisandrin B (SchB) has been extensively used to treat diverse liver diseases, its therapeutic efficacy on ALI was limited due to its high hydrophobicity. Palmitic acid-modified serum albumin (PSA) is not only an effective carrier for hydrophobic drugs, but also has a superb targeting effect via scavenger receptor-A (SR-A) on the M1 macrophages, which are potential therapeutic targets for ALI. Compared with the common macrophage-targeted delivery systems, PSA enables site-specific drug delivery to reduce off-target toxicity. Herein, we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI. In vitro, compared with human serum albumin encapsulated SchB nanoparticles (SchB-HSA NPs), the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide (LPS) stimulated Raw264.7 (LAR) cells, and LAR cells took up PSA NPs 8.79 times more than HSA NPs. As expected, the PSA NPs also accumulated more in the liver. Moreover, SchB-PSA NPs dramatically reduced the activation of NF-κB signaling, and significantly relieved inflammatory response and hepatic necrosis. Notably, the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%. Hence, SchB-PSA NPs are promising to treat ALI.

While single-atom catalysts offer well-defined structures, the homogeneity of the active sites is determined by localized coordination environments. Here, authors anchor Ir single atoms onto different sites on CoOOH and show how their distinct coordinations activate oxygen-evolving electrocatalysis

As endogenous courier vesicles, exosomes play crucial roles in macromolecule transmission and intercellular communication. Therefore, exosomes have drawn increasing attention as biomimetic drug-delivery vehicles over the past few years. However, few studies have investigated the encapsulation of peptide/protein drugs into exosomes for oral administration. Additionally, the mechanisms underlying their biomimetic properties as oral delivery vehicles remain unknown. Herein, insulin-loaded milk-derived exosomes (EXO@INS) were fabricated and the in vivo hypoglycemic effect was investigated on type I diabetic rats. Surprisingly, EXO@INS (50 and 30 IU/kg) elicited a more superior and more sustained hypoglycemic effect compared with that obtained with subcutaneously injected insulin. Further mechanism studies indicated that the origin of excellent oral-performance of milk-derived exosomes combined active multi-targeting uptake, pH adaptation during gastrointestinal transit, nutrient assimilation related ERK1/2 and p38 MAPK signal pathway activation and intestinal mucus penetration. This study provides the first demonstration that multifunctional milk-derived exosomes offer solutions to many of the challenges arising from oral drug delivery and thus provide new insights into developing naturally-equipped nanovehicles for oral drug administration.

The research and application of CO2 storage and enhanced oil recovery (EOR) have gradually emerged in China. However, the vast unconventional oil and gas resources are stored in reservoir pores ranging from several nanometers to several hundred micrometers in size. Additionally, CO2 geological sequestration involves the migration of fluids in tight caprock and target layers, which directly alters the transport and phase behavior of reservoir fluids at different scales. Micro- and nanoscale fluidics technology, with their advantages of in situ visualization, high temperature and pressure resistance, and rapid response, have become a new technical approach to investigate gas–liquid interactions in confined domains and an effective supplement to traditional core displacement experiments. The research progress of micro–nano fluidics visualization technology in various aspects, such as CO2 capture, utilization, and storage, is summarized in this paper, and the future development trends and research directions of micro–nano fluidics technology in the field of carbon capture, utilization, and storage (CCUS) are predicted.

Wettability, as a vital tool for analyzing and describing oil flow, plays a significant role in determining oil/water relative permeability, residual oil distribution, and on–site recovery efficiency. Although the contact angle method is widely used for measuring wetting behavior, it is susceptible to the effects of surface roughness, oil–water saturation, and the distribution of mixed wetting within the range of droplet sizes. Additionally, millimeter–scale droplets fail to accurately represent the wetting distribution and the influencing factors at the micro/nano–scale. Therefore, this study presents a comprehensive investigation of the microstructure and wettability of shale samples. The characterization of the samples was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques to gain insights into their microscopic features, surface properties, and wettability. Results demonstrate the following: (1) Quartz and clay minerals tended to exhibit rough surface topography, appearing as darker areas (DA) under scanning electron microscopy (SEM). It is worth noting that plagioclase minerals exhibited brighter areas (BA) under SEM. (2) An increase in the content of minerals such as quartz and clay minerals was observed to decrease the surface oil wetting behavior. In contrast, plagioclase feldspar exhibited an opposite trend. (3) Based on the adhesive forces of the samples towards oil or water, a wetting index, I, was established to evaluate the wettability of shale at a microscale. The dimensionless contact angle W, obtained by normalizing the contact angle measurement, also consistently indicated oil wetting behavior. (4) By comparing the differences between I and W, it was observed that surface roughness significantly affected the behavior of water droplets. The presence of roughness impeded the contact between the solid and liquid phases, thus influencing the accuracy of the wetting results. Organic matter also plays a significant role in influencing surface wettability, and its distribution within the shale samples can lead to localized variations in wettability.

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.

Recent research has demonstrated that parametric quantum circuits (PQCs) are affected by gradients that progressively vanish to zero as a function of the number of qubits. We show that using a combination of gradient-free natural evolutionary strategy and gradient descent can mitigate the possibility of optimizing barren plateaus in the landscape. We implemented 2 specific methods: natural evolutionary strategy stochastic gradient descent (NESSGD) and natural evolutionary strategy adapting the step size according to belief in observed gradients (NESAdaBelief) to optimize PQC parameter values. They were compared with standard stochastic gradient descent, adaptive moment estimation, and a version of adaptive moment estimation adapting the step size according to belief in observed gradients in 5 classification tasks. NESSGD and NESAdaBelief demonstrated some superiority in 4 of the tasks. NESAdaBelief showed higher accuracy than AdaBelief in all 5 tasks. In addition, we investigated the applicability of NESSGD under the parameter shift rule and demonstrated that NESSGD can adapt to this rule, which means that our proposed method could also optimize the parameters of PQCs on quantum computers.

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthropathy with a high deformity rate. Despite numerous studies and clinical trials, no curative treatment is available for large weight-bearing joints. Intra-articular (IA) injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity. However, free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease. Herein, a phospholipids-based controlled-release gel was prepared for sustained IA delivery of celastrol (CEL) and the therapeutic efficiency was evaluated in a rheumatoid arthritis rabbit model. The CEL-loaded gel (CEL-gel) contained up to 70% phospholipids yet was easy to inject. After injecting into the joint cavity, CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent. In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel. A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution (CEL-sol). Furthermore, the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL. With good biocompatibility and biodegradability, CEL-gel might be a promising IA drug delivery system.

Substantial variation in the environment directly causes remodeling of the colonized gut microbiota, controlling community diversity, and functions in the host to tune-up their adaptive states. However, the mechanisms of microbial community assembly in response to environmental changes remain unclear, especially in endangered ruminants. In this study, we analyzed the microbial communities of 37 fecal samples collected from captive and wild Alpine musk deer (Moschus chrysogaster) to characterize the complexity and assembly processes using 16S rRNA gene sequencing. We found significantly different diversities and compositions of gut microbiota among both groups associated with different living environments. Heterogeneous selection was the predominant factor regulating the gut microbiota community under similar climatic conditions, indicating that microbial community assembly was largely driven by deterministic mechanisms. The species co-occurrence network showed complex and tight connections with a higher positive correlation in the wild environment. Moreover, the captive group exhibited significant differences in chemoheterotrophy and fermentation compared with the wild group, but the opposite was observed in animal parasites or symbionts, which might be closely related to diet, energy supply, and healthcare of animals. This study provides a framework basis and new insights into understanding gut microbiota in different environments.

Photodynamic therapy (PDT) is highly effective in treating tumors located near body surface, offering strong tumor suppression and low damage to normal tissue nearby. PDT is also effective for treating a number of other conditions. PDT not only provide a precise and selective method for the treatment of various diseases by itself, it can also be used in combination with other traditional therapies. Because PDT uses light as the unique targeting mechanism, it has simpler and more direct targeting capability than traditional therapies. The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances. Different photosensitizers have their distinct characteristics, leading to different advantages and disadvantages. These could be enhanced or compensated by using proper PDT system. Therefore, the selected type of photosensitizer would heavily influence the overall design of a PDT system. In this article, we evaluated major types of inorganic and organic PDT photosensitizers, and discussed future research directions in the field.

Metastasis is closely related to the high mortality of cancer patients, which is regulated by multiple signaling pathways. Hence, multiphase blocking of this biological process is beneficial for cancer treatments. Herein, we establish a multifunctional self-delivering system by synthesizing D-α-tocopheryl succinates (TOS)-conjugated chondroitin sulfate (CS) (CT NPs), which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade. TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9, while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets. The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade. Following encapsulating chemotherapeutic drug doxorubicin (DOX), the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice. As a result, the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases.

Nlrp3 inflammasome activation requires Nek7 recruitment to drive ASC speck formation. Here the authors show how Nlrp3 phosphorylation events control this Nek7 recruitment.

The molecular compositions of oil-bearing fluid inclusions (FIs) are valuable for the research of oil and gas accumulation; however, due to the very trace amount of materials included, the requirements of commercial instruments cannot be satisfied and thus custom designed instruments were needed for this method, which is difficult to be achieved and the application for the molecular composition of FIs have been limited. In this paper, three samples of oil-bearing FIs were analyzed by pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) to obtain their hydrocarbon composition. The first sample was a synthetic inclusion prepared by the occlusion of a small amount of crude oil from the Halibut oil field, the second sample was from Australian Jabiru oil field and the third sample was collected from the Tahe oil field in the northwestern China. A diverse range of aliphatic compounds, including n-alkanes, mono-, di- and tricyclic aromatic hydrocarbons and other components have been successively detected from these materials of which, the n-alkanes were monitored up to carbon numbers over C30. Also, the results showed that the method introduced here gave comparable molecular characteristics with data obtained from other traditional methods. The mature degree calculated from Py-GC-MS is very close to that of MCI method. However, it is also notable that the thermal maturity parameters calculated from the results of inclusion analysis were much lower than those of crude oil, indicating modification caused by late-stage alteration to oils in reservoir. As a conventional and easy performed analytical method specially designed for the degradation of macromolecule, the Py-GC-MS demonstrated here is also suitable for the analysis of FIs.

Abstract Most Alzheimer’s disease drugs do not work efficiently because of the blood–brain barrier. Therefore, we designed a new nanopreparation (PS-DZP-CHP): cholesterol-modified pullulan (CHP) nanoparticle with polysorbate 80(PS) surface coverage, as donepezil (DZP) carrier to realize brain tissue delivery. By size analysis and isothermal titration calorimetry, we chose the optimal dosing ratio of the drug with nanomaterials (1:5) and designed a series of experiments to verify the efficacy of the nanoparticles. The results of in vitro release experiments showed that the nanoparticles can achieve continuous drug release within 72 h. The results of fluorescence observation in mice showed a good brain targeting of PS-DZP-CHP nanoparticles. Furthermore, the nanoparticle can enhance the drug in the brain tissue concentration in mice. DZP-CHP nanoparticles were used to pretreat nerve cells with Aβ protein damage. The concentration of lactate dehydrogenase was determined by MTT, rhodamine 123 and AO-EB staining, which proved that DZP-CHP nanoparticles had a protective effect on the neurotoxicity induced by Aβ25–35 and were superior to free donepezil. Microthermal perpetual motion meter test showed that PS-DZP-CHP nanoparticles have an affinity with apolipoprotein E, which may be vital for this nanoparticle targeting to brain tissue.

Gut microbiota are essential to maintain host health and fitness largely through its influence with behavior, development and reproduction of host, particular among the amniotic ectothermic reptiles. Global warming effects on the composition of the host's gut microbiota in some taxa are generally known. Previous studies on reptiles in both natural habitats and lab-reared individuals have demonstrated that temperature changes can alter the composition and function of the host's gut microbiota. However, these effects on wild-caught reptiles are not well-understood. This study investigated changes in the composition of gut microbiota of wild-caught lizards (Eremias argus), which were experimentally exposed to two different temperatures. The results showed that the increase in temperature altered the gut microbiota; both the groups showed an altered and destabilized composition of gut microbiota in response to their adaptive states. The warming did not significantly alter the relative abundances of the main gut microbial communities in both the lizard genders, but increased those of predicted pathogenic bacterial genera, including Acinetobacter, Anaerotruncus, and Dehalobacterium. These results provided insights into the ecological adaptations of Eremias argus, but the body health and fitness of wild populations, concerning temperature changes, warrant further investigations.

Celastrol might be useful in treating rheumatoid arthritis in part by inhibiting apoptosis of macrophages; however, systemic toxicity is a concern. Here the authors design celastrol-loaded nanoparticles that release a payload in response to MMP9 cleavage and show these NPs are effective at inducing apoptosis of human macrophages in vitro and a therapeutic effect with an adjuvant-induced arthritis model in rats.