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Abstract In eukaryotes, topologically associating domains (TADs) organize the genome into functional compartments. While TAD-like structures are common in mammals and many plants, they are challenging to detect in Arabidopsis thaliana. Here, we demonstrate that Arabidopsis PDS5 proteins play a negative role in TAD-like domain formation. Through Hi-C analysis, we show that mutations in PDS5 genes lead to the widespread emergence of enhanced TAD-like domains throughout the Arabidopsis genome, excluding pericentromeric regions. These domains exhibit increased chromatin insulation and enhanced chromatin interactions, without significant changes in gene expression or histone modifications. Our results suggest that PDS5 proteins are key regulators of genome architecture, influencing 3D chromatin organization independently of transcriptional activity. This study provides insights into the unique chromatin structure of Arabidopsis and the broader mechanisms governing plant genome folding.

Abstract Dynamic axion insulators feature a time-dependent axion field that can be induced by antiferromagnetic resonance. Here, we show that a Josephson junction incorporating this dynamic axion insulator between two superconductors exhibits striking doubled Shapiro steps wherein all odd steps are completely suppressed in the joint presence of a DC bias and a static magnetic field. The resistively shunted junction simulation confirms that these doubled Shapiro steps originate from the distinctive axion electrodynamics driven by the antiferromagnetic resonance, which thus not only furnishes a hallmark to identify the dynamic axion insulator but also provides a method to evaluate its mass term. Furthermore, the experimentally feasible differential conductance is also determined. Our work holds significant importance in condensed matter physics and materials science for understanding the dynamic axion insulator, paving the way for its further exploration and applications.

Through the analysis of natural gas composition, carbon and hydrogen isotopes of alkane gases, reservoir bitumen, source rock conditions, and source–reservoir combinations, this study clarifies the differences in gas sources and the origins of natural gas in the Permian Changxing Formation–Triassic Feixianguan Formation on both sides of the Kaijiang–Liangping Trough. Additionally, it identifies favorable exploration directions for coal-formed gas generated by the Longtan Formation in the Sichuan Basin. The following understanding was obtained: (1) The natural gas in the Changxing–Feixianguan formations mainly composed of alkane gas, typical of dry gas. (2) The carbon isotope values of methane and ethane in the Changxing–Feixianguan formations on the east side of the trough are lower than those on the west side. Specifically, the ethane carbon isotope value in the Longgang Gas Field on the west side is higher than that in the Yuanba Gas Field, while the methane hydrogen isotope value is lower in the Longgang Gas Field compared to the Yuanba Gas Field. (3) The natural gas in the Dongyuezhai, Puguang, and Yuanba gas fields predominantly originates from sapropelic organic matter of the Wujiaping Formation, with kerogen types II1–I; in contrast, the Longgang Gas Field contains a mixture of coal-formed gas and oil-type gas, with a slightly higher content of coal-formed gas, originating from mixed organic matter of the Wujiaping Formation, with kerogen type II1–II2. (4) Multiple types of gas, such as coal rock gas, tight sandstone gas, and shale gas, can be formed within the Longtan Formation. The Suining–Luzhou and Langzhong–Guang'an–Fuling areas are identified as favorable zones for the exploration of coal rock gas and marine–continental transitional shale gas, respectively. Additionally, the reef and shoal development areas of the Changxing Formation in the Suining–Hechuan and Guang'an–Nanchong regions are also favorable exploration areas for coal-formed gas.

Based on the “unidirectional break-up and convergence” geodynamic model, this study investigates the impact of the evolution of the Tethyan domain on the formation of petroleum systems in the Sichuan super basin and explores the enrichment pattern of natural gas. The results show that, firstly, the Sichuan Basin and its surrounding areas have experienced two unidirectional rifting-aggregation cycles triggered by the Proto-Tethys Ocean and the Paleo-Tethys Ocean during the Neoproterozoic to Triassic. During Jurassic–Cenozoic, the Sichuan Basin is incorporated in the circum-Tibetan plateau basin-mountain coupled tectonic domain system. The episodic tectonic movements within the plate control the sedimentary infill styles. Second, the evolution of the Tethyan domain, paleoclimatic environment and major geological events controlled the formation and distribution of high-quality source rocks within the basin. The rift valley and intracratonic rift, passive continental margin slope, and intracratonic sags are favorable areas for the development of source rocks. Third, the evolution of the Tethyan domain, supercontinent cycles, global sea level changes, and tectono-climatic events controlled the distribution of carbonate platform and reservoir-caprock combinations. The cratonic platform margins and sub-platform internal high terrains are key areas for finding carbonate high-energy facies belts. Syndepositional paleo-uplifts and surrounding slopes, regional unconformities, and later faults zone are areas where large-scale carbonate reservoirs are distributed. The regional evaporite or shale caprock are beneficial for the large-scale preservation of oil and gas in the basin. Fourth, the spatio-temporal matching relationship of reservoir forming factors influenced by the early tectonic-sedimentary evolution pattern and the degree of later tectonic modification is the key to oil and gas enrichment. Future oil and gas exploration should focus on potential gas systems during the Sinian rift period, Cambrian pre-salt gas systems in the eastern and southern Sichuan, as well as whole oil and gas systems of Permian and Triassic.

Abstract IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host’s defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

Abstract Background Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. Results Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months [95% CI: 7.2–12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. Conclusion β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.

Abstract Heterochromatin de-condensation in companion gametic cells is conserved in both plants and animals. In plants, microspore undergoes asymmetric pollen mitosis (PMI) to produce a vegetative cell (VC) and a generative cell (GC). Subsequently, the GC undergoes pollen mitosis (PMII) to produce two sperm cells (SC). Consistent with heterochromatin de-condensation in the VC, H3K9me2, a heterochromatin mark, is barely detected in VC. However, how H3K9me2 is differentially regulated during pollen mitosis remains unclear. Here, we show that H3K9me2 is gradually evicted from the VC since PMI but remain unchanged in the GC and SC. ARID1, a pollen-specific transcription factor that facilitates PMII, promotes H3K9me2 maintenance in the GC/SC but slows down its eviction in the VC. The genomic targets of ARID1 mostly overlaps with H3K9me2 loci, and ARID1 recruits H3K9 methyltransferase SUVH6. Our results uncover that differential pattern of H3K9me2 between two cell types is regulated by ARID1 during pollen mitosis.

Abstract Objective This study aims to investigate the anatomical structure of the C6 pedicle and lateral mass in children aged 0–14 years using CT imaging, providing detailed insights into their growth and development. Methods We conducted a comprehensive measurement of C6. Measurements included width, length, and height of the pedicles, as well as the length, width, and thickness of the lateral masses, and several angular metrics. Regression analysis was performed to understand the growth trends, and statistical analyses were carried out to identify differences between age groups, genders, and sides. Results In children younger than four years, the pedicle width exceeds its height, influencing the diameter of the pedicle screws. By age two to three, the pedicle height and lateral mass thickness reaches 3.0 mm, allowing for the use of 3.0 mm diameter screws. The pedicle transverse angle remains stable. Most parameters showed no significant differences between the left and right sides. Size parameters exhibited significant larger in males than females at ages 0–1, 3–7, and 10–12 years. Regression analysis revealed that the growth trends of size parameters follow cubic or polynomial curves. Most angular metrics follow cubic fitting curves without a clear trend of change with age. Conclusion This study provides a detailed analysis of the anatomical development of the C6 pedicle and lateral masses in children, offering valuable insights for pediatric cervical spine surgeries. The findings highlight the importance of considering age-specific anatomical variations when planning posterior surgical fixation, specifically at C6. It is necessary for us to perform thin-layer CT scans on children and carefully measure various indicators before surgery.

Abstract Objective To evaluate the safety of first-line systemic therapy for metastatic colorectal cancer through network meta-analysis. Methods The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the inception of the databases to August 15, 2023, and strict inclusion and exclusion criteria were applied to screen studies. The Cochrane Bias Risk Assessment Tool (RoB 2.0) was used to evaluate the quality of the included literature. Network meta-analysis was conducted using Stata 15.0 and R4.3.1 software to compare the incidence of adverse events (AEs) among different treatment regimens. Results A total of 53 randomized controlled trials, involving 17,351 patients with metastatic colorectal cancer (mCRC), were ultimately included, encompassing 29 different therapeutic approaches. According to SUCRA rankings, the CAPOX regimen is most likely to rank first in terms of safety, while the FOLFOXIRI + panitumumab regimen is most likely to rank last. In terms of specific AEs, the CAPOX regimen, whether used alone or in combination with targeted drugs (bevacizumab and cetuximab), is associated with a reduced risk of neutropenia and febrile neutropenia, as well as an increased risk of thrombocytopenia and diarrhea. The FOLFOX regimen, with or without bevacizumab, is linked to an increased risk of neutropenia and peripheral sensory neuropathy. The FOLFIRI/CAPIRI + bevacizumab regimen is associated with a reduced risk of peripheral sensory neuropathy. S-1 and S-1 + oxaliplatin are well-tolerated in terms of gastrointestinal reactions. The FOLFOXIRI regimen, whether used alone or in combination with targeted drugs, is associated with various AEs. Conclusion In summary, the CAPOX regimen may be the safest option among the first-line systemic treatment regimens for mCRC patients, while the FOLFOXIRI + panitumumab regimen may be associated with a higher incidence of grade 3 or higher AEs.

Abstract Objective There were few reports in the literature regarding hidden blood loss following surgery for developmental dysplasia of the hip in children. This study aimed to evaluate the volume of hidden blood loss and its risk factors among children undergoing hip reconstruction for developmental dysplasia of the hip. Methods A retrospective analysis of clinical data from 42 patients (58 hips), who underwent Pemberton and femoral osteotomies between March 2020 and March 2023, was conducted. Serial complete blood count assays were conducted on the day of admission and four days post-surgery. Preoperative and postoperative hematocrit levels were documented to calculate hidden blood loss utilizing the Gross formula. Pearson and Spearman correlation analyses, along with multivariable linear regression, were employed to ascertain associations between patient characteristics and hidden blood loss. Results The mean hidden blood loss was recorded as 283.06 ± 271.05 mL, constituting 70.22% of the total blood loss. Multiple linear regression analysis identified weight and surgical duration as independent risk factors contributing to hidden blood loss. Conclusions A relevant amount of postoperative hidden blood loss occurs after Pemberton osteotomy and femoral osteotomy for developmental dysplasia of the hip. Surgeons should be aware that patients who require blood transfusions and have longer surgical durations are at a higher risk of developing more hidden blood loss. Therefore, attention should be given to hidden blood loss to ensure patient safety during the perioperative period for those undergoing Pemberton and femoral osteotomies. Level of evidence IV.

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

ABSTRACT: Whey protein isolate (WPI)-based nanodelivery systems have recently attracted an increasing amount of attention. Despite this, research focusing on milk protein concentrate (MPC) and micellar casein (MCC) as carriers loaded in hydrophobic compounds is lacking. This study investigated the mediated effect of docosahexaenoic acid (DHA) in 3 different milk proteins for the embedding of astaxanthin (ASTA) after ultrasound-assisted pH-shifting treatment. We then evaluated the application of milk protein carriers in cheese processing by comparing MPC, MCC, and WPI. The particle size, polydispersity index, and zeta potential results of the milk protein–DHA complex suggested that the addition of 0.36 μmol/mL DHA optimized the delivery of milk protein to ASTA. All 3 DHA-mediated milk proteins induced an improvement in encapsulation efficiency and antioxidant properties of ASTA. Furthermore, the DHA-mediated MPC and MCC played a stronger role in improving the bioaccessibility and thermal and storage stability of ASTA than those without DHA. Tests conducted to examine the application in cheese production indicated that MCC carrier had a positive effect on the texture of cheeses. However, the delivery effect was dependent on the milk protein variety, and MCC exhibited the best protection ability of ASTA, followed by MPC and WPI. The simulated digestion and storage stability results of cheese further confirmed that the protein encapsulation mediated by DHA was more conducive to ASTA absorption. These findings suggested that the DHA-mediated milk protein complexes studied here may be suitable hydrophilic delivery carriers for the hydrophobic nutrient ASTA, potentially playing different roles in improving its storage stability and bioaccessibility.

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an unpredictable course of recurrent exacerbations alternating with more stable disease. SLE is characterized by broad immune activation and autoantibodies against double-stranded DNA and numerous proteins that exist in cells as aggregates with nucleic acids, such as Ro60, MOV10, and the L1 retrotransposon-encoded ORF1p. Results Here we report that these 3 proteins are co-expressed and co-localized in a subset of SLE granulocytes and are concentrated in cytosolic dots that also contain DNA: RNA heteroduplexes and the DNA sensor ZBP1, but not cGAS. The DNA: RNA heteroduplexes vanished from the neutrophils when they were treated with a selective inhibitor of the L1 reverse transcriptase. We also report that ORF1p granules escape neutrophils during the extrusion of neutrophil extracellular traps (NETs) and, to a lesser degree, from neutrophils dying by pyroptosis, but not apoptosis. Conclusions These results bring new insights into the composition of ORF1p granules in SLE neutrophils and may explain, in part, why proteins in these granules become targeted by autoantibodies in this disease.

Abstract Objective Explore the feasibility of a mobile health(mHealth) and virtual reality (VR) based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. Methods We recruited cancer patients in the Oncology department of the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University from October 2022 to April 2023. The rehabilitation program was provided by a team of medical oncologists, dietitians, psychotherapists, and oncology specialist nurses. Participants received standard anti-cancer therapy and integrated intervention including hospitalized group-based exercise classes, at-home physical activity prescription, behavior change education, oral nutrition supplements, and psychological counseling. An effective intervention course includes two consecutive hospitalization and two periods of home-based rehabilitation (8 weeks). Access the feasibility as well as changes in aspects of physical, nutritional, and psychological status. Results At the cutoff date of April 2023, the recruitment rate was 75% (123/165). 11.4%patients were lost to follow-up, and 3.25% withdrew halfway. Respectively, the completion rate of nutrition, exercise, and psychology were 85%,55%, and 63%. Nutrition interventions show the highest compliance. The parameters in nutrition, psychology, muscle mass, and quality of life after the rehabilitation showed significant improvements (P .05) in handgrip strength and 6-minute walking speed. Conclusion It is feasible to conduct mHealth and VR-based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. A larger multi-center trial is warranted in the future. Trial registration ChiCTR2200065748 Registered 14 November 2022.

Abstract Background Acute pancreatitis is one of the most common diseases requiring emergency surgery. Rapid and accurate recognition of acute pancreatitis can help improve clinical outcomes. This study aimed to develop a deep learning-powered diagnostic model for acute pancreatitis. Materials and methods In this investigation, we enrolled a cohort of 190 patients with acute pancreatitis who were admitted to Sichuan Provincial People’s Hospital between January 2020 and December 2021. Abdominal computed tomography (CT) scans were obtained from both patients with acute pancreatitis and healthy individuals. Our model was constructed using two modules: (1) the acute pancreatitis classifier module; (2) the pancreatitis lesion segmentation module. Each model’s performance was assessed based on precision, recall rate, F1-score, Area Under the Curve (AUC), loss rate, frequency-weighted accuracy (fwavacc), and Mean Intersection over Union (MIOU). Results Upon admission, significant variations were observed between patients with mild and severe acute pancreatitis in inflammatory indexes, liver, and kidney function indicators, as well as coagulation parameters. The acute pancreatitis classifier module exhibited commendable diagnostic efficacy, showing an impressive AUC of 0.993 (95%CI: 0.978–0.999) in the test set (comprising healthy examination patients vs. those with acute pancreatitis, P

Abstract During shield tunneling in highly abrasive formations such as sand–pebble strata, nonuniform wear of shield cutters is inevitable due to the different cutting distances. Frequent downtimes and cutter replacements have become major obstacles to long‐distance shield driving in sand–pebble strata. Based on the cutter wear characteristics in sand–pebble strata in Beijing, a design methodology for the cutterhead and cutters was established in this study to achieve uniform wear of all cutters by the principle of frictional wear. The applicability of the design method was verified through three‐dimensional simulations using the engineering discrete element method. The results show that uniform wear of all cutters on the cutterhead could be achieved by installing different numbers of cutters on each trajectory radius and designing a curved spoke with a certain arch height according to the shield diameter. Under the uniform wear scheme, the cutter wear coefficient is greatly reduced, and the largest shield driving distance is increased by approximately 47% over the engineering scheme. The research results indicate that the problem of nonuniform cutter wear in shield excavation could be overcome, thereby providing guiding significance for theoretical innovation and construction of long‐distance shield excavation in highly abrasive strata.

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-AOE@NV). The incorporation of JAM-AOE@NV into a thermosensitive hydrogel matrix (JAM-AOE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-AOE@NV, and resulted in the achievement of a sustained-release profile for JAM-AOE@NV. The physicochemical characteristics of the JAM-AOE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-AOE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.

Abstrcat: Basal cell carcinoma (BCC) of the prostate is a rare and enigmatic tumor with uncertain biological behavior and treatment modalities. Some studies suggest that BCC exhibits invasive characteristics and a high degree of malignancy, necessitating proactive management and vigilant monitoring. Notably, there is a lack of reported effective treatment utilizing programmed cell death protein-1 (PD-1) inhibitors for advanced BCC of the prostate. This study explores the efficacy of tislelizumab, as a single-agent therapy, in the successful treatment of advanced prostate BCC.

Objectives The use of awake extracorporeal membrane oxygenation (ECMO, without intubation or sedation under ECMO support in patients with cardiogenic shock is growing rapidly because emerging clinical investigations indicates it may reduce morbidity associated with sedation and intubation. We systematically reviewed the efficacy of awake ECMO and provided evidence for clinical practitioners and researchers.Design Systematic review and trial sequential meta-analysis based on observational studies.Data sources Data was retrieved from seven databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database and Cochrane Library) up to 1 March 2024.Eligibility criteria We included observational studies that compared the differences in clinical outcomes between awake ECMO and non-awake ECMO in patients with cardiogenic shock.Data extraction and synthesis Two reviewers rigorously conducted literature retrieval, screening and data extraction. The RevMan software was used for data synthesis.Results Five retrospective observational studies involving 1044 patients with cardiogenic shock were included. Compared with non-awake ECMO, awake ECMO was associated with a lower mortality rate of patients with cardiogenic shock (OR=0.28; 95% CI, (0.15, 0.49); p

Tandem duplications significantly influence the diversity of the human genome and the occurrence of many complex diseases. However, accurate detection of tandem duplications of low coverage remains a challenging task. Based on RD (read depth), the tandem duplication detection method assumes that there is a linear relationship between the RD value and the tandem duplication number in the region in the genome. However, at low coverage, the RD values of tandem duplication regions and normal regions in the sequencing sample are not significantly different, and it will affect the performance of tandem duplication detection. Therefore, relying on traditional statistical models based on RD strategy to detect tandem duplications often leads to relative low precision and recall. For solving this problem, we propose a new method for identifying tandem duplications in whole-genome sequencing data.TD-COF, a tandem duplication detection method, utilizes the COF (Connectivity-Based Outlier Factor) algorithm. Considering the relative connectivity between intervals in the genome, the algorithm applies a connectivity factor to each bin to calculate its outlier score Additionally, TD-COF introduces the Split Read strategy into RD-based methods, enabling precise identification of the start and end points of tandem duplications down to the level of individual bases. Furthermore, TD-COF incorporates mapping quality as a feature signal. The bins with lower mapping quality are assigned higher outlier values, effectively mitigating interference from mapping errors. Simulation experiments demonstrate that TD-COF outperforms other methods in terms of sensitivity, precision and F1 score. And, TD-COF exhibits high consistency with other methods when applied to real sequencing samples. This study indicates that TD-COF is an effective method for detecting tandem duplications even in regions of low or moderate coverage. In summary, we consider the TD-COF to be an effective method for detecting tandem duplications.

In the realm of renewable energy, the integration of wind power and hydrogen energy systems represents a promising avenue towards environmental sustainability. However, the development of cost-effective hydrogen energy storage solutions is crucial to fully realize the potential of hydrogen as a renewable energy source. By combining wind power generation with hydrogen storage, a comprehensive hydrogen energy system can be established. This study aims to devise a physiologically inspired optimization approach for designing a standalone wind power producer that incorporates a hydrogen energy system on a global scale. The optimization process considers both total cost and capacity loss to determine the optimal configuration for the system. The optimal setup for an off-grid solution involves the utilization of eight distinct types of compact horizontal-axis wind turbines. Additionally, a sensitivity analysis is conducted by varying component capital costs to assess their impact on overall cost and load loss. Simulation results indicate that at a 15 % loss, the cost of energy (COE) is $1.3772, while at 0 % loss, it stands at $1.6908. Capital expenses associated with wind turbines and hydrogen storage systems significantly contribute to the overall cost. Consequently, the wind turbine-hydrogen storage system emerges as the most cost-effective and reliable option due to its low cost of energy.

BackgroundWhile sarcopenia has been found to be associated with increased risks of cardiovascular diseases (CVDs), evidence exploring sex-related differences remains insufficient. This study aimed to investigate the differences in how often sarcopenia occurs in each sex, as determined by skeletal muscle area (SMA) in chest CT images, and its association with CVD common risk factors.MethodsThis cross-sectional study involved 1,340 inpatients from the Department of Geriatrics of Renji Hospital, affiliated to Shanghai Jiaotong University School of Medicine. Data on age, sex, body mass index (BMI), smoking status, disease history, and clinical parameters were collected. Sarcopenia was defined using chest CT images with a cut-off value of T12-SMA/height2

The characteristics of elements, isotopes, and small shelly fossils were investigated for Late Ediacaran to Early Cambrian stratigraphy division and to discuss their geological implications in the northwestern Sichuan Basin. The results reveal that small shelly fossils can be detected in the high-phosphorous section, with the concentration of phosphorus mainly ranging from 2% to 8%, suggesting that this interval belongs to the Early Cambrian, which is also consistent with the carbon isotopic composition results. In addition, the Early Cambrian is denudated in the Sichuan Basin due to tectonic movement, and the characteristics of some isotopes and small shell fossils are different from those in other basins. It can be proposed that P content can support the recognition of lithological boundaries, and the high phosphorus content can be used as a reference to identify the top and bottom boundaries of the Maidiping Formation in the study area. According to the elemental compositions in the Ediacaran Dengying Formation, the variations in Si, Al, Fe, and K contents are similar in the platform area and rift area, suggesting that the third and fourth member of the Dengying Formation are also developed in the Deyang–Anyue Rift. The results suggest that both the Deng-4 member and Maidiping Formation feature contemporaneous deposition of different facies in the northwestern Sichuan Basin. The strata consist of shale intercalated with thin carbonate rock deposits in the Deyang–Anyue Rift, while carbonate rock deposits in the platform. The Deyang–Anyue Rift expanded gradually in the Late Ediacaran and eventually filled in the Early Cambrian. The data in this study illustrate that elemental compositions, isotopes, and small shelly fossils can be combined to correlate the Late Ediacaran to Early Cambrian strata and provide new evidence for Deyang–Anyue Rift evolution. The results offer some new insights for deep oil and gas exploration in the Sichuan Basin and for the tectonic–depositional–environmental–biological synergistic evolution in the Late Ediacaran to Early Cambrian transition.

Abstract Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.

Abstract Background The use of gene therapy to deliver microRNAs (miRNAs) has gradually translated to preclinical application for the treatment of intervertebral disc degeneration (IDD). However, the effects of miRNAs are hindered by the short half-life time and the poor cellular uptake, owing to the lack of efficient delivery systems. Here, we investigated nucleus pulposus cell (NPC) specific aptamer-decorated polymeric nanoparticles that can load miR-150-5p for IDD treatment. Methods The role of miR-150-5p during disc development and degeneration was examined by miR-150-5p knockout (KO) mice. Histological analysis was undertaken in disc specimens. The functional mechanism of miR-150-5p in IDD development was investigated by qRT-PCR assay, Western blot, coimmunoprecipitation and immunofluorescence. NPC specific aptamer-decorated nanoparticles was designed, and its penetration, stability and safety were evaluated. IDD progression was assessed by radiological analysis including X-ray and MRI, after the annulus fibrosus needle puncture surgery with miR-150-5p manipulation by intradiscal injection of nanoparticles. The investigations into the interaction between aptamer and receptor were conducted using mass spectrometry, molecular docking and molecular dynamics simulations. Results We investigated NPC-specific aptamer-decorated polymeric nanoparticles that can bind to miR-150-5p for IDD treatment. Furthermore, we detected that nanoparticle-loaded miR-150-5p inhibitors alleviated NPC senescence in vitro, and the effects of the nanoparticles were sustained for more than 3 months in vivo. The microenvironment of NPCs improves the endo/lysosomal escape of miRNAs, greatly inhibiting the secretion of senescence-associated factors and the subsequent degeneration of NPCs. Importantly, nanoparticles delivering miR-150-5p inhibitors attenuated needle puncture-induced IDD in mouse models by targeting FBXW11 and inhibiting TAK1 ubiquitination, resulting in the downregulation of NF-kB signaling pathway activity. Conclusions NPC-targeting nanoparticles delivering miR-150-5p show favorable therapeutic efficacy and safety and may constitute a promising treatment for IDD. Graphical Abstract

Abstract Axion insulators possess a quantized axion field θ = π protected by combined lattice and time-reversal symmetry, holding great potential for device applications in layertronics and quantum computing. Here, we propose a high-spin axion insulator (HSAI) defined in large spin-s representation, which maintains the same inherent symmetry but possesses a notable axion field θ = (s + 1/2)2 π. Such distinct axion field is confirmed independently by the direct calculation of the axion term using hybrid Wannier functions, layer-resolved Chern numbers, as well as the topological magneto-electric effect. We show that the guaranteed gapless quasi-particle excitation is absent at the boundary of the HSAI despite its integer surface Chern number, hinting an unusual quantum anomaly violating the conventional bulk-boundary correspondence. Furthermore, we ascertain that the axion field θ can be precisely tuned through an external magnetic field, enabling the manipulation of bonded transport properties. The HSAI proposed here can be experimentally verified in ultra-cold atoms by the quantized non-reciprocal conductance or topological magnetoelectric response. Our work enriches the understanding of axion insulators in condensed matter physics, paving the way for future device applications.

Immunoprecipitation (IP) coupled with mass spectrometry effectively maps protein–protein interactions when genome-wide, affinity-tagged cell collections are used. Such studies have recorded significant portions of the compositions of physiological protein complexes, providing draft ’interactomes’; yet many constituents of protein complexes still remain uncharted. This gap exists partly because high-throughput approaches cannot optimize each IP. A key challenge for IP optimization is stabilizing in vivo interactions during the transfer from cells to test tubes; failure to do so leads to the loss of genuine interactions during the IP and subsequent failure to detect. Our high-content screening method explores the relationship between in vitro chemical conditions and IP outcomes, enabling rapid empirical optimization of conditions for capturing target macromolecular assemblies.

Abstract Background Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. Methods In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. Results In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p

Background Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI.Methods We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs).Results A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time.Conclusions Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Abstract Background Mecapegfilgrastim, a long‐acting granulocyte‐colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. Objective We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S‐1/capecitabine‐based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Method Five hundred and sixty‐one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. Results The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S‐1/capecitabine‐based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S‐1/capecitabine‐based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. Conclusion In a real‐world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high‐risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

IntroductionOdontoid incidence (OI) is an important parameter that has recently been developed. However, there are currently no studies on OI in adolescent idiopathic scoliosis (AIS) patients. We aimed to examine the significance of OI in describing cervical sagittal alignment in AIS patients, explore the differences in cervical sagittal parameters among these patients with different curve types, and investigate the correlations between coronal deformity and cervical sagittal parameters in AIS patients.MethodsThe whole-spine anteroposterior and lateral plain radiographs of AIS patients were retrospectively analyzed. The parameters, including OI, odontoid tilt (OT), C2 slope, cervical lordosis (CL), T1 slope (T1S), and others, were measured. The AIS patients were grouped based on different curve types. Measurement parameters were compared between different groups. Pearson correlation analysis was performed for cervical sagittal parameters and Cobb angle.ResultsNinety AIS patients were included, consisting of 14 males and 76 females. The main thoracic curve group exhibited a smaller OI compared to the main thoracolumbar/lumbar curve group (P

Backgroundβ-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of β-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma.MethodsThis is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received β-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy.ResultsA total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum.ConclusionsThis preliminary study demonstrates that β-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety.Clinical Trial RegistrationChinese Clinical Trials Registry, identifier ChiCTR2100044088

Recent regional investigations in the United States have revealed a thought-provoking perspective: household electricity consumption may act as an inferior commodity, displaying a negative correlation with wealth. This finding challenges the outcomes of various other econometric analyses and underscores the importance of scrutinizing power consumption patterns across different regional service areas. While it is commonly believed that home electricity usage decreases as income rises, this may not always hold true universally. This study focuses on power usage in Seattle, Washington households, a prominent urban economy in the Pacific Northwest. Employing dynamic error correction modeling techniques, the research demonstrates statistically significant fluctuations in domestic power usage attributed to variations in actual value, actual revenue, and cold weather. In the immediate future, energy for homes in this urban economy resembles any other commodity. However, investing in electricity for homes in Seattle may not be advisable in the long run. Home power usage in Seattle declines with each percentage point increase in actual per capita income over 1.2 %. This finding highlights the need for careful consideration and strategic planning in energy management policies for urban economies like Seattle.

Mulberry leaf protein (MLP) is a nutrient-rich protein, but its applicability is limited because of its poor solubility. To address this issue, this study combines MLP with whey protein isolates (WPI), known for the high nutritional value, and subsequently forms composite protein nanoparticles using the ultrasound-assisted pH shifting method. Microscopic observation and SDS-PAGE confirmed the binding between these two proteins. Fluorescence spectra and Fourier Transform infrared spectroscopy (FTIR) analysis supported the involvement of electrostatic interactions, hydrophobic attractions, and hydrogen bonding in the formation of stable complex nanoparticles. The interactions between the proteins became stronger after ultrasound-assisted pH-shifting treatment. Solubility, emulsification capacity, foaming, and antioxidant activity, among other indicators, demonstrate that the prepared composite nanoparticles exhibit favorable functional properties. The study successfully illustrates the creation of protein-based complex nanoparticles through the ultrasound-assisted pH shifting method, with potential applications in the delivery of bioactive compounds.

Background Tandem duplication (TD) is a common and important type of structural variation in the human genome. TDs have been shown to play an essential role in many diseases, including cancer. However, it is difficult to accurately detect TDs due to the uneven distribution of reads and the inherent complexity of next-generation sequencing (NGS) data. Methods This article proposes a method called DTDHM (detection of tandem duplications based on hybrid methods), which utilizes NGS data to detect TDs in a single sample. DTDHM builds a pipeline that integrates read depth (RD), split read (SR), and paired-end mapping (PEM) signals. To solve the problem of uneven distribution of normal and abnormal samples, DTDHM uses the K-nearest neighbor (KNN) algorithm for multi-feature classification prediction. Then, the qualified split reads and discordant reads are extracted and analyzed to achieve accurate localization of variation sites. This article compares DTDHM with three other methods on 450 simulated datasets and five real datasets. Results In 450 simulated data samples, DTDHM consistently maintained the highest F1-score. The average F1-score of DTDHM, SVIM, TARDIS, and TIDDIT were 80.0%, 56.2%, 43.4%, and 67.1%, respectively. The F1-score of DTDHM had a small variation range and its detection effect was the most stable and 1.2 times that of the suboptimal method. Most of the boundary biases of DTDHM fluctuated around 20 bp, and its boundary deviation detection ability was better than TARDIS and TIDDIT. In real data experiments, five real sequencing samples (NA19238, NA19239, NA19240, HG00266, and NA12891) were used to test DTDHM. The results showed that DTDHM had the highest overlap density score (ODS) and F1-score of the four methods. Conclusions Compared with the other three methods, DTDHM achieved excellent results in terms of sensitivity, precision, F1-score, and boundary bias. These results indicate that DTDHM can be used as a reliable tool for detecting TDs from NGS data, especially in the case of low coverage depth and tumor purity samples.

Summary: Lymph node metastasis (LNM) is the main metastatic pathway of cervical cancer, which is closely related to 5-year survival rate of cervical squamous cell carcinoma (CSCC), yet the underlying mechanism remains unconfirmed. In this study, we show that midkine (MDK) was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM. Functional investigations demonstrated that MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells (HLECs). MDK exerted these biological effects by interacting with Syndecan-1 and activating PI3K/AKT and p38 MAPK pathways. A retrospective study showed that s-MDK was related to LNM. s-MDK combined with serum-squamous cell carcinoma antigen(s-SCCA) improved the diagnostic accuracy of CSCC LNM. These findings established a new mechanism of LNM and highlighted MDK as a candidate tumor biomarker and therapeutic target in CSCC.

Background: Management guidelines for acute lung injury (ALI) are extremely limited. Xuebijing, a traditional Chinese medicine, exerts therapeutic effects in patients with ALI; however, supportive evidence is currently insufficient. Material and methods: A systematic literature search of seven electronic databases for randomised controlled trials assessing the efficacy of Xuebijing injections in patients with ALI, published from inception to March 31, 2024, was performed. The Risk of Bias assessment tool recommended by The Cochrane Collaboration was used for quality evaluation. Review Manager version 5.3 (R Foundation for Statistical Computing, Vienna, Austria) was used for analysis. Dichotomous variables are expressed as relative risk (RR) and continuous variables as standardised mean difference (SMD). Heterogeneity was assessed using the I2 statistic and a funnel plot was used to visually assess publication bias. Results: Sixteen studies comprising 1327 patients were included. Xuebijing injection improved oxygenation index (SMD 1.08 [95 % confidence interval (CI) 0.79–1.38]), reduced the incidence of acute respiratory distress syndrome (RR 0.56 [95 % CI 0.42–0.74) and all-cause mortality (RR 0.48 [95 % CI 0.34–0.67]), and decreased serum tumor necrosis factor-alpha (SMD -1.33 [95 % CI -1.50 to −1.17]) and interleukin-6 levels (SMD -1.35 [95 % CI -1.52 to −1.17]). The funnel plot indicated no publication bias. Conclusion: Xuebijing injection may be an effective treatment for ALI. However, this needs to be further confirmed in well-designed, large-sample, randomised controlled trials.

ObjectiveEarly identification of cognitive impairment in older adults could reduce the burden of age-related disabilities. Gait parameters are associated with and predictive of cognitive decline. Although a variety of sensors and machine learning analysis methods have been used in cognitive studies, a deep optimized machine vision-based method for analyzing gait to identify cognitive decline is needed.MethodsThis study used a walking footage dataset of 158 adults named West China Hospital Elderly Gait, which was labelled by performance on the Short Portable Mental Status Questionnaire. We proposed a novel recognition network, Deep Optimized GaitPart (DO-GaitPart), based on silhouette and skeleton gait images. Three improvements were applied: short-term temporal template generator (STTG) in the template generation stage to decrease computational cost and minimize loss of temporal information; depth-wise spatial feature extractor (DSFE) to extract both global and local fine-grained spatial features from gait images; and multi-scale temporal aggregation (MTA), a temporal modeling method based on attention mechanism, to improve the distinguishability of gait patterns.ResultsAn ablation test showed that each component of DO-GaitPart was essential. DO-GaitPart excels in backpack walking scene on CASIA-B dataset, outperforming comparison methods, which were GaitSet, GaitPart, MT3D, 3D Local, TransGait, CSTL, GLN, GaitGL and SMPLGait on Gait3D dataset. The proposed machine vision gait feature identification method achieved a receiver operating characteristic/area under the curve (ROCAUC) of 0.876 (0.852–0.900) on the cognitive state classification task.ConclusionThe proposed method performed well identifying cognitive decline from the gait video datasets, making it a prospective prototype tool in cognitive assessment.

Squamous cell carcinoma (SCC) is a prevalent malignancy affecting multiple organs in the human body, including the oral cavity, esophagus, cervix, and skin. Given its significant incidence and mortality rates, researchers are actively seeking effective diagnostic and therapeutic strategies. In recent years, exosomes and their molecular cargo, particularly circular RNA (circRNA), have emerged as promising areas of investigation in SCC research. Exosomes are small vesicles released into the extracellular environment by cells that contain biomolecules that reflect the physiological state of the cell of origin. CircRNAs, known for their unique covalently closed loop structure and stability, have garnered special attention in oncology and are closely associated with tumorigenesis, progression, metastasis, and drug resistance. Interestingly, exosomal circRNAs have been identified as ideal biomarkers for noninvasive cancer diagnosis and prognosis assessment. This article reviews the progress in research on exosomal circRNAs, focusing on their expression patterns, functions, and potential applications as biomarkers in SCC, aiming to provide new insights and strategies for the diagnosis and treatment of SCC.

BackgroundKlebsiella pneumoniae is a common Gram-negative bacterium. Blood infection caused by K. pneumoniae is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by K. pneumoniae bloodstream infection has not been studied.MethodsA total of 13 subjects were included in this study, 3 healthy controls, 7 patients with K. pneumoniae bloodstream infection in the acute stage (4 patients died), and 3 patients in the recovery stage. Peripheral blood of all patients was collected and PBMCs were isolated for scRNA-seq analysis. We studied the changes of PBMCs components, signaling pathways, differential genes, and cytokines in acute and recovery stages.ResultsDuring K. pneumoniae acute infection we observed a decrease in the proportion of T cells, most probably due to apoptosis and the function of T cell subtypes was disorder. The proportion of monocytes increased in acute stage. Although genes related to their phagocytosis function were upregulated, their antigen presentation capacity-associated genes were downregulated. The expression of IL-1β, IL-18, IFNGR1 and IFNGR2 genes was also increased in monocytes. The proportion of DCs was depleted during the acute stage and did not recover during sepsis recovery. DCs antigen presentation was weakened during the acute stage but recovered fast during the recovery stage. pDCs response to MCP-1 chemokine was weakened, they recovered it quickly during the recovery stage. B cells showed apoptosis both in the acute stage and recovery stage. Their response to complement was weakened, but their antigen presentation function was enhanced. The proportion of NK cells stable during all disease’s stages, and the expression of IFN-γ gene was upregulated.ConclusionThe proportion of PBMCs and their immune functions undergo variations throughout the course of the disease, spanning from the acute stage to recovery. These findings provide new insights into the mechanism of PBMCs immune function during K. pneumoniae bloodstream infection sepsis and recovery and sets the basis for further understanding and treatment.

Novel nano-heterojunctions with excellent antibacterial properties are regarded as effective alternatives to antibiotics for bacterial disinfection. Herein, we have developed a universal strategy to synthesize a series of urchin-shaped Prussian blue analogues@Prussian blue (PBA@PB) nano-heterojunctions via a facile co-precipitation route for efficient bacterial disinfection, for the first time, which could overcome the disadvantages of singe PBA or PB. The optimized PBA@PB nano-heterojunctions showed remarkable bactericidal efficiency ability against multi drug-resistant (MDR) Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA), (99.4% and 98.8% bactericidal ratios, respectively), attributed to their outstanding photothermal and catalytic performance. It should be emphasized that the as-prepared nano-heterojunctions also showed amazing bacterial elimination efficiency in sewage. The antibacterial mechanism was also investigated using a variety of spectroscopic and microscopic techniques. It can be attributed to the formation of unique nano-heterojunctions between PB and PBA, which improves the absorption of NIR light and facilitates the separation of generated electron-hole pairs. Therefore, the urchin-shaped PBA@PB nano-heterojunctions may be promising candidates for rapidly bacterial elimination in environmental remedy and wastewater treatment.

Abstract Despite having significant applications in the construction of controlled delivery systems with high anti-interference capability, to our knowledge dual-controlled molecular release has not yet been achieved based on small molecular/supramolecular entities. Herein, we report a dual-controlled release system based on coordination cages, for which releasing the guest from the cage demands synchronously altering the coordinative metal cations and the solvent. The cages, Hg 5 L 2 and Ag 5 L 2 , are constructed via coordination-driven self-assembly of a corannulene-based ligand. While Hg 5 L 2 shows a solvent-independent guest encapsulation in all the studied solvents, Ag 5 L 2 is able to encapsulate the guests in only some of the solvents, such as acetone-d6, but will liberate the encapsulated guests in 1,1,2,2-tetrachloroethane-d2. Hg 5 L 2 and Ag 5 L 2 are interconvertible. Thus, the release of guests from Hg 5 L 2 in acetone-d6 can be achieved, but requires two separate operations, including metal substitutions and a change of the solvent. Dual-controlled systems as such could be useful in complicated molecular release process to avoid those undesired stimulus-responses.

Abstract Many countries and regions in the world have obtained industrial oil flow in the Meso-Neoproterozoic sedimentary strata and formed commercial exploitation in recent years. The development horizon of high-quality source rocks in the Proterozoic in North China can be compared with the international, indicating that the Meso-Neoproterozoic in North China has great exploration potential. The sedimentary characteristics of typical aulacogen in multiple cratons in the Meso-Neoproterozoic North China Craton are compared and studied by using field outcrop data, drilling data and analysis and test data, aiming to provide sedimentary support for the prediction of oil and gas distribution and evaluation of exploration field in the Meso-Neoproterozoic in this area. The results show that there are four sedimentary systems in the study area, including Marine clastic rock sedimentary system, Marine carbonate sedimentary system, Marine-continental transitional facies sedimentary system and glacial sedimentary system. They are divided into seven sedimentary facies types: barrier coastal facies, non-barrier coast facies, shallow shelf facies, carbonate platform facies, reef facies, fan delta facies and glacial facies, and further divided into 15 subfacies and 21 microfacies. On this basis, the Meso-Neoproterozoic sedimentary filling sequences of two typical aulacogens, Yanliao and Xiong 'er, in the study area are clarified, showing that the formation time of each sedimentary filling sequence stage of different aulacogens is different, and the rock characteristics, lithology combination, lithologic structure, contact relationship, vertical sequence and sedimentary facies assemblage of the same sedimentary filling sequence stage are obviously different. The filling characteristics of the two aulacogens completely record the geological events related to the breakup of the Colombian supercontinent.

Abstract The nuclear matrix is a nuclear compartment that has diverse functions in chromatin regulation and transcription. However, how this structure influences epigenetic modifications and gene expression in plants is largely unknown. In this study, we show that a nuclear matrix binding protein, AHL22, together with the two transcriptional repressors FRS7 and FRS12, regulates hypocotyl elongation by suppressing the expression of a group of genes known as SMALL AUXIN UP RNAs (SAURs) in Arabidopsis thaliana. The transcriptional repression of SAURs depends on their attachment to the nuclear matrix. The AHL22 complex not only brings these SAURs, which contain matrix attachment regions (MARs), to the nuclear matrix, but it also recruits the histone deacetylase HDA15 to the SAUR loci. This leads to the removal of H3 acetylation at the SAUR loci and the suppression of hypocotyl elongation. Taken together, our results indicate that MAR-binding proteins act as a hub for chromatin and epigenetic regulators. Moreover, we present a mechanism by which nuclear matrix attachment to chromatin regulates histone modifications, transcription, and hypocotyl elongation.

Based on the global basement reservoir database and the dissection of basement reservoirs in China, the characteristics of hydrocarbon accumulation in basement reservoirs are analyzed, and the favorable conditions for hydrocarbon accumulation in deep basement reservoirs are investigated to highlight the exploration targets. The discovered basement reservoirs worldwide are mainly buried in the Archean and Precambrian granitic and metamorphic formations with depths less than 4 500 m, and the relatively large reservoirs have been found in rift, back-arc and foreland basins in tectonic active zones of the Meso-Cenozoic plates. The hydrocarbon accumulation in basement reservoirs exhibits the characteristics in three aspects. First, the porous-fractured reservoirs with low porosity and ultra-low permeability are dominant, where extensive hydrocarbon accumulation occurred during the weathering denudation and later tectonic reworking of the basin basement. High resistance to compaction allows the physical properties of these highly heterogeneous reservoirs to be independent of the buried depth. Second, the hydrocarbons were sourced from the formations outside the basement. The source-reservoir assemblages are divided into contacted source rock-basement and separated source rock-basement patterns. Third, the abnormal high pressure in the source rock and the normal–low pressure in the basement reservoirs cause a large pressure difference between the source rock and the reservoirs, which is conducive to the pumping effect of hydrocarbons in the deep basement. The deep basement prospects are mainly evaluated by the factors such as tectonic activity of basement, source-reservoir combination, development of large deep faults (especially strike-slip faults), and regional seals. The Precambrian crystalline basements at the margin of the intracontinental rifts in cratonic basins, as well as the Paleozoic folded basements and the Meso-Cenozoic fault-block basements adjacent to the hydrocarbon generation depressions, have favorable conditions for hydrocarbon accumulation, and thus they are considered as the main targets for future exploration of deep basement reservoirs.

The Ediacaran–Ordovician strata within three major marine basins (Tarim, Sichuan, and Ordos) in China are analyzed. Based on previous studies focusing on the characteristics of the Neoproterozoic–Cambrian strata within the three major basins (East Siberian, Oman, and Officer in Australian) overseas, the carbonate–evaporite assemblages in the target interval are divided into three types: intercalated carbonate and gypsum salt, interbedded carbonate and gypsum salt, and coexisted carbonate, gypsum salt and clastic rock. Moreover, the concept and definition of the carbonate–evaporite assemblage are clarified. The results indicate that the oil and gas in the carbonate–evaporite assemblage are originated from two types of source rocks: shale and argillaceous carbonate, and confirmed the capability of gypsum salt in the saline environment to drive the source rock hydrocarbon generation. The dolomite reservoirs are classified in two types: gypsum-bearing dolomite flat, and grain shoal & microbial mound. This study clarifies that the penecontemporaneous or epigenic leaching of atmospheric fresh water mainly controlled the large-scale development of reservoirs. Afterwards, burial dissolution transformed and reworked the reservoirs. The hydrocarbon accumulation in carbonate-evaporite assemblage can be categorized into eight sub-models under three models (sub-evaporite hydrocarbon accumulation, supra-evaporite hydrocarbon accumulation, and inter-evaporite hydrocarbon accumulation). As a result, the Cambrian strata in the Tazhong Uplift North Slope, Maigaiti Slope and Mazatag Front Uplift Zone of the Tarim Basin, the Cambrian strata in the eastern-southern area of the Sichuan Basin, and the inter-evaporite Ma-4 Member of Ordovician in the Ordos Basin, China, are defined as favorable targets for future exploration.

Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass (Mømitohigh) and fibrosis. Among the Mømitohigh subpopulation of CD206+ M2, characterized by higher expression of dynamin 1-like (Drp1), as determined by flow cytometry and RNA-seq analysis, a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics. A pathfinder exosome called “exosomeMMP19 (ExoMMP19)”, was constructed to display matrix metalloproteinase-19 (MMP19) on the surface to locally break down the excessive extracellular matrix (ECM) in the fibrotic lung. A therapeutic exosome called “exosome therapeutics (ExoTx)”, was engineered to display D-mannose on the surface while encapsulating siDrp1 inside. Prior delivery of ExoMMP19 degraded excessive ECM and thus paved the way for ExoTx to be delivered into Mømitohigh, where ExoTx inhibited mitochondrial fission and alleviated PF. This study has not only identified Mømitohigh as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.