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Abstract Background High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. Case presentation A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. Conclusions Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

At the altitude of low-Earth-orbiting satellites, most details of lithospheric magnetic anomalies observed near surface are attenuated, and only slowly decaying long-wavelength magnetic anomalies can be detected. Long-wavelength magnetic anomalies are generated by large-scale magnetized rocks in the Earth's crust and uppermost mantle at depths shallower than the Curie depth. Interpretation of such lithospheric magnetic anomalies has been used in geological mapping, crustal composition and structure studies, plate tectonic reconstruction, and geodynamics. To introduce the origin of long-wavelength magnetic anomalies at a global scale, we first reviewed satellite magnetic anomaly maps in early periods and calculated anomaly maps using four main lithospheric magnetic field models, including the CHAOS-7, CM6, MF7, and CSES models. Then, based on the result of the CHAOS-7 model at 500 km altitude, 29 long-wavelength magnetic anomalies with amplitudes greater than 4 nT were identified and their geological origins were reviewed. Among these, there were twenty magnetic anomalies over continents and nine over the ocean. The long-wavelength magnetic anomalies over continental areas were mostly located in Precambrian basements related to the Archean nuclei, Proterozoic terrane, and iron-rich formations, with a few located in the orogenic background. The long-wavelength magnetic anomalies in the ocean region were all located in oceanic plateau, generally related to the breakup of Gondwana during the Cretaceous Period, and have the characteristics of thickened crust. Hence, the long-wavelength magnetic anomalies reveal a significant magnetization difference in the deep crust during crustal growth, a key issue that requires further study. Compared to satellite magnetic surveys in some other nations, detecting lithospheric magnetic anomalies by satellite started relatively late in China. The China Seismo-Electromagnetic Satellite (CSES) was launched in February 2018. It was China's first satellite designed to monitor earthquakes with multiple geophysical payloads, including magnetometers capable of measuring weak signals from the lithosphere. The Macau Science Satellite-1 (MSS-1) was launched in 2023 and is specially used for monitoring the geomagnetic field in low latitudes. Furthermore, a subsequent CSES-02 satellite is planned to be launched in 2024. With the vigorous development of satellite magnetic surveys in China, it is expected that progressively more Chinese researchers will pay attention to long-wavelength magnetic anomalies and promote the study of their origin.

Low Earth orbit (LEO) satellites have emerged as a primary tool for global geomagnetic field detection and model refinement, owing to their wide coverage, high resolution, and absence of geographical limitations. This paper provides a comprehensive review of the history, key characteristics, measurement accuracy, and future trends in LEO satellite magnetic field measurements. The first part of the paper outlines the evolution of LEO satellites, highlighting their unique advantages. The focus then shifts to the calibration methodology for in-orbit LEO satellite magnetic measurements, with a specific emphasis on vector magnetic field intrinsic calibration and alignment algorithms. Calibration results are presented to demonstrate the effectiveness of these methodologies. In the third section, the paper introduces the theory behind global geomagnetic field modeling. An overview of current global geomagnetic field models is provided, encompassing their sources, spatial resolutions, and other relevant attributes. The paper concludes by presenting the global morphology and features of the main field, lithospheric field, magnetospheric, and ionospheric field. Despite the significant progress enabled by LEO satellite technology, global geomagnetic field modeling faces challenges such as limited spatio-temporal resolution. To address this, incorporating near-surface observation data and continuously optimizing modeling technology are deemed essential solutions.

In markets for beef and sheep meat, an appropriate level of intramuscular fat (IMF) is highly desirable for meat-eating quality, but strategies to improve it usually lead to an undesirable excess in carcase fat, presenting a major challenge to livestock producers. To solve this problem, we need to understand the partitioning of fat among the major fat depots: IMF, subcutaneous fat (SCF) and visceral fat (VF). In most genotypes of cattle and sheep, the rate of accretion is lower for IMF than for SCF and VF, so genetic selection for a high level of IMF, or the use of an increased dietary energy supply to promote IMF deposition, will increase overall fatness and feed costs. On the other hand, feeding postnatal calves with excessive concentrates promotes IMF deposition, so a nutritional strategy is feasible. With genetic strategies, several problems arise: 1) positive genetic correlations between IMF, SCF and VF differ among genotypes in both cattle and sheep; 2) genotypes appear to have specific, characteristic rates of accretion of IMF during periods of growth and fattening; 3) most breeds of cattle and sheep naturally produce meat with relatively low levels of IMF, but IMF does vary substantially among individuals and breeds so progress is possible through accurate measurement of IMF. Therefore, an essential prerequisite for selection will be knowledge of the genetic correlations and fat accretion rates for each genotype. Currently, selection for IMF is based on existing technology that directly measures IMF in the progeny or siblings, or estimates IMF in live animals. New technology is needed to permit the simultaneous measurement of SCF and IMF in the field, thus opening up the possibility of accurate selection, particularly for fat partitioning in live animals. Specifically, there would be great value in detecting individuals with an IMF advantage at an early age so the generation interval could be shortened and genetic gain accelerated. Genetic gain would also be greatly aided if we could select for genes that control adipogenesis and lipogenesis and are also differentially expressed in the various depots.

Abstract Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.

Abstract Objectives To develop and validate radiomics model based on computed tomography (CT) for preoperative prediction of CN0 status in patients with papillary thyroid carcinoma (PTC). Methods A total of 548 pathologically confirmed LNs (243 non-metastatic and 305 metastatic) two distinct hospitals were retrospectively assessed. A total of 396 radiomics features were extracted from arterial-phase CT images, where the strongest features containing the most predictive potential were further selected using the least absolute shrinkage and selection operator (LASSO) regression method. Delong test was used to compare the AUC values of training set, test sets and cN0 group. Results The Rad-score showed good discriminating performance with Area Under the ROC Curve (AUC) of 0.917(95% CI, 0.884 to 0.950), 0.892 (95% CI, 0.833 to 0.950) and 0.921 (95% CI, 868 to 0.973) in the training, internal validation cohort and external validation cohort, respectively. The test group of CN0 with a AUC of 0.892 (95% CI, 0.805 to 0.979). The accuracy was 85.4% (sensitivity = 81.3%; specificity = 88.9%) in the training cohort, 82.9% (sensitivity = 79.0%; specificity = 88.7%) in the internal validation cohort, 85.4% (sensitivity = 89.7%; specificity = 83.8%) in the external validation cohort, 86.7% (sensitivity = 83.8%; specificity = 91.3%) in the CN0 test group.The calibration curve demonstrated a significant Rad-score (P-value in H-L test > 0.05). The decision curve analysis indicated that the rad-score was clinically useful. Conclusions Radiomics has shown great diagnostic potential to preoperatively predict the status of cN0 in PTC.

Long-wavelength (>500 km) magnetic anomalies originating in the lithosphere were first found in satellite magnetic surveys. Compared to the striking magnetic anomalies around the world, the long-wavelength magnetic anomalies in China and surrounding regions are relatively weak. Specialized research on each of these anomalies has been quite inadequate; their geological origins remain unclear, in particular their connection to tectonic activity in the Chinese and surrounding regions. We focus on six magnetic high anomalies over the (1) Tarim Basin, (2) Sichuan Basin (3) Great Xing’an Range, (4) Barmer Basin, (5) Central Myanmar Basin, and (6) Sunda and Banda Arcs, and a striking magnetic low anomaly along the southern part of the Himalayan-Tibetan Plateau. We have analyzed their geological origins by reviewing related research and by detailed comparison with geological results. The tectonic backgrounds for these anomalies belong to two cases: either ancient basin basement, or subduction-collision zone. However, the geological origins of large-scale regional magnetic anomalies are always subject to dispute, mainly because of limited surface exposure of sources, later tectonic destruction, and superposition of multi-phase events.

Abstract This paper presents a novel detection and rerouting mechanism for distributed adaptive platoon control of non‐linear autonomous connected vehicles under denial of service (DoS) attacks. DoS attacks can cause delays or losses of data packets due to blocked communication channels, leading to reducing platoon performance or even collisions among vehicles. To tackle this issue, the proposed mechanism detects and reroutes communication topology depending on the real‐time topology and the number of link failures. Real‐time detection divides the scenario of DoS attacks into three parts. According to the different scenarios, rerouting mechanisms will be utilized. A controller adapted to real‐time variable communication topology is also designed in this scheme. The adjacency matrix of the real‐time communication topology generated by the rerouting mechanism is used to update the controller so that the platoon can remain in a stable state without being affected by DoS attacks. In addition, the sliding mode controller and the observer are designed by solving linear matrix inequalities, and the platoon stability and internal stability are proven. Numerical simulation studies demonstrate that the proposed mechanism and control design can reduce the vehicle state estimate error and platoon‐tracking error to ideal states under DoS attacks. The proposed method solves the problem that the existing methods have not considered the number of link failures and the inability to restore communication when the communication topology is paralyzed.

Formic acid is regarded to be one of the most prospective hydrogen carriers. Effective screening of the fitting non-noble-metal-based heterogeneous catalysts to substitute the expensive noble-metal-based ones for FA dehydrogenation is considered as a key to the commercial application for hydrogen economics. Herein, dehydrogenation of liquid neat FA achieved a gas production value of 1753.5 mL/gcat./h at 94 °C by using a biomass-derived γ-Mo2N based catalyst synthesized from the earth-abundant molybdenum and soybean with a facile pyrolysis process. The effect of material ratio, pyrolysis temperature on the catalytic performance of FA dehydrogenation were studied in details. In particular, the catalyst obtained at a pyrolysis temperature of 700 °C, weight ratios of ammonium molybdate to soybean of 0.2/1 exhibited the highest activity. In addition, the catalytic activity increased with the increase of FA concentration, but conversely, the dehydrogenation selectivity decreased with the increasing FA concentration. Moreover, it was found that the Bio-Mo2N catalyst was rather stable over the 40 h continuous reaction period.

Increasingly, progestins are being detected in aquatic environments, especially in aquaculture areas, and concern about their adverse effects on aquatic organisms is growing. However, the mechanisms underlying progestin-induced oxidative stress and the antioxidant response of aquatic invertebrates to progestin exposure are unknown. Researchers recently reported that norgestrel (NGT) likely causes oxidative stress in the clam Mactra veneriformis. In this study, we assessed reactive oxygen species (ROS) levels, antioxidant enzyme activity, malonaldehyde content, ultrastructure, and DNA damage in the digestive gland of M. veneriformis exposed to 7.69 or 756.62 ng/L of NGT for 21 days. We also conducted tandem mass tag-based quantitative proteomic analysis to detect the protein response and gain insights into response mechanisms in clams exposed to NGT. We found that NGT enhanced oxidative phosphorylation via the wingless/integrated signaling pathway and triggered ROS generation. The alterations of antioxidant enzyme activities suggested that these enzymes are involved in scavenging NGT-induced ROS. NGT weakened antioxidant defense by suppressing the antioxidant synthesis-related AMP-activated protein kinase/forkhead box O and sirtuin 1/forkhead box O pathways. Additionally, cell membrane dissolution, mitochondrial cristae rupture, DNA damage, elevation of malonaldehyde content, and oxidation of lipid, protein, and glucose occurred due to compromised redox homeostasis. Our results highlight the oxidative stress, antioxidant response, and oxidative damage induced by NGT in M. veneriformis and shed light on ecological risks of progestins to aquatic invertebrates.

Abstract Understanding the motion of charged particles in the electromagnetic field in the inner magnetosphere is essential for space science and space weather. Charge accumulation can occur due to the dipole magnetic and convective electric fields in this region. However, until the recent Magnetospheric Multiscale (MMS) mission, there were few means to detect charge distribution in situ. We report unambiguous in situ observation of the spatial distribution of the excess charge density in the inner magnetosphere by the MMS mission. We find that a positive (negative) charge accumulates in the dusk (dawn) side inner magnetospheres, which is contrary to the long assumed overall quasi-neutrality of space plasma. These observations and results offer insight into magnetosphere–ionosphere coupling.

AbstractBackground At present, there are no available genetic data on the AGCU EX22 Kit from the Wuhu Han population.Aim This study investigates the applicability of the AGCU EX22 kit, designed for the Chinese population for forensic analysis and population genetics of the Wuhu Han population.Subjects and methods Bloodstains from 1565 unrelated healthy individuals in Wuhu city, Anhui Province, were collected for analysis. The AGCU EX22 kit was used for amplification, and capillary electrophoresis was used to separate the amplification products. Allele frequencies and forensic parameters were determined. The Wuhu Han population was compared to 10 reference populations through genetic distance, a phylogenetic neighbor-joining tree and principal component analysis.Results In total, 281 alleles and 1187 genotypes were observed. No significant deviations from Hardy-Weinberg equilibrium at any locus were found after Bonferroni’s correction. The 21 autosomal short tandem repeat (STR) genetic markers exhibited high informativeness and polymorphism. The cumulative power of discrimination and power of exclusion were 0.999999999999999999999999913380 and 0.999999996752339, respectively. Population comparisons revealed a genetic affinity between Wuhu Han and southern Han populations, except for the Guangdong Han population, which aligned with the traditional geographical division in China.Conclusion The AGCU EX22 Kit, containing 21 STR loci, is suitable for forensic application and population genetics studies in the Wuhu Han population.

Purpose: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3–6 years. Methods: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P < 0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95 % CI, 0.008–0.117, P < 0.001 and OR, 0.204; 95 % CI, 0.055–0.763, P = 0.018, respectively) by multivariate binary logistic regression analysis. SE changing process represented the changes of SE, Myopia group had bigger SE changes (P < 0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changing process in total participants, Non-myopia group and Myopia group (B = 0.234, P < 0.001; B = 0.078, P = 0.010; B = 0.161, P = 0.046, respectively) Conclusions: Initial SE and the length of macular BM in pre-myopia children aged 3–6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changing process.

Purpose: To evaluate temporal vascular arcade angle and its influencing factors in myopic children. Methods: It was a retrospective study, we reviewed the records of 119 patients aged 6–10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year). Results: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys. Conclusion: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future.

The goal of this study was to evaluate the trace element pollution in a marine ranching area in China based on molecular responses (expression of metallothionein and antioxidant enzyme genes), and biochemical biomarkers (metallothionein content, antioxidant enzyme activities, and malonaldehyde level) in four indicator species. We collected samples of two fish (Lateolabrax maculatus and Sebastes schlegelii), one crustacean (Charybdis japonica), and one gastropod (Rapana venosa) from the western Furong Island marine ranching area and from an adjacent area in March 2022 and measured the trace element content in these indicator species as well as in the seawater and sediment. We found that the bioaccumulation characteristics of trace elements and the response patterns of biomarkers were species specific. Moreover, not every biomarker was significantly correlated with environmental trace element content. We then established two biomarker combinations indicative of trace element pollution in seawater and sediment, respectively, based on the correlation between biomarkers and trace element contents. The selected biomarkers were integrated using integrated biomarker response version 2 (IBRv2). IBRv2 values in the studied marine ranching area were lower than those in the adjacent area. Additionally, these values were consistent with the bioaccumulation of trace elements in the indicator species, the integrated trace element pollution index for seawater, and the potential risk index for sediment. These results show that this multi-biomarker and multi-species IBRv2 approach provided a comprehensive diagnosis of trace element pollution in the marine ranching area. Therefore, its application may be beneficial for marine environmental monitoring and management in view of the ecotoxicological impact of pollutants on organisms.

Summary: Constitutive explorations indicate a correlation between circular RNAs (circRNAs) and cardiovascular diseases. However, the involvement of circRNAs in endothelial recuperation and in-stent restenosis (ISR) remains underexplored. CircTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs). Here, we identified that circTMEM165 was downregulated in ISR patients, inversely correlating with ISR severity. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation, and adhesion. Particularly, we first observed that circTMEM165 could alleviate HUVECs apoptosis and mitochondrial fission induced by lipopolysaccharide (LPS). Mechanistically, circTMEM165, as a miR-192-3p sponge, enhancing SCP2 expression, which serves as a critical regulator of HUVECs biological functions. Moreover, in vivo, circTMEM165 attenuated intimal hyperplasia and facilitated repair following classic rat carotid artery balloon injury model. These findings investigated the circTMEM165-miR-192-3p-SCP2 axis as a critical determinant of endothelial health and a potential biomarker and therapeutic target for vascular disorders.

Abstract Diatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana.

Post-translational modifications (PTM) are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids. PTMs play essential roles in biological function and regulation and have been linked with several diseases. Modifications of protein acylation (Kac), a type of PTM, are known to induce epigenetic regulatory processes that promote various diseases. Thus, an increasing number of studies focusing on acylation modifications are being undertaken. Butyrylation (Kbu) is a new acylation process found in animals and plants. Kbu has been recently linked to the onset and progression of several diseases, such as cancer, cardiovascular diseases, diabetes, and vascular dementia. Moreover, the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels, suggesting that butyrylation may play a therapeutic role in these diseases. In addition, butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth, development, and metabolism of rice. The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated. This study reviews the potential role of histone Kbu, as well as the mechanisms underlying this process. It also summarizes various enzymes and analytical methods associated with Kbu, with the goal of providing new insights into the role of Kbu in gene regulation and diseases.

This study investigated the spatiotemporal distribution of the phytoplankton in the coral habitat of Dongshan Bay (China), along with critical factors affecting the distribution, during June, August, and December 2022. Phytoplankton abundance in Dongshan Bay exhibited considerably temporal variation, peaking in June 2022, gradually decreasing thereafter, and reaching its lowest point in December 2022. The abundance of bottom-layer phytoplankton consistently exceeded that of the surface layer throughout all seasons. The average phytoplankton abundance in the coral habitat of Dongshan Bay was lower than that in non-coral habitat areas. Fluctuations in the Zhangjiang River and coastal upwelling influenced the diversity and community structure of the phytoplankton. Critical factors causing spatiotemporal variability in phytoplankton community structure included nutrient concentrations and seawater temperature. Nutrients played key roles in influencing various phytoplankton groups. Dominant diatom species, such as Thalassionema nitzschioides and Thalassiosira diporocyclus, were positively correlated with ammonia nitrogen, seawater salinity, coral cover, and the number of coral species present. In winter, Calanus sinicus exhibited a negative correlation with harmful algal bloom species. Additionally, it was found that both in the coral habitat and surrounding open sea, currents, nutrients, and zooplankton may play crucial roles in determining the spatiotemporal variability in the phytoplankton community structure.

Occupational therapy is a profession with origins rooted in Western values. As culture plays an important role in shaping theory and practice, the curriculum design of academic programs that train future rehabilitation professionals should reflect the local context. As part of an international partnership, a dual-degree graduate program in occupational therapy was established between a Chinese and an American university. A team composed of members from both institutions collaborated on culturally adapting an entry-level master’s program in occupational therapy for China, based on a U.S. program, which welcomed its first cohort in September 2019. This article details the timeline and process of program design and adaptation from conception, through implementation to evaluation and revision, with the aim of offering a framework for curriculum adaptation of other academic programs in the U.S. and internationally. The adapted curriculum includes the program mission, vision, and philosophy; the curriculum model with program outcomes and threads; the program scope and sequence; materials and resources; and course-specific objectives, learning activities, and assessments. The authors also share lessons learned through this experience of international collaboration as well as next steps for program evaluation and sustainability. The detailed overview of this international collaboration offers suggestions for individuals and institutions seeking to develop global partnerships and adapt curricula across cultural contexts.

In May 2020, a bottom-trawl survey in the southern Bohai Sea collected the portunid crab Charybdis bimaculata, a species formerly found in the northern Yellow Sea. In subsequent surveys, C. bimaculata was found to be abundant and likely to occupy habitats and niches of native species. To study the suitability of habitat in the southern Bohai Sea for this crab, nine trawl surveys were conducted between 2020 and 2022 to monitor its dispersal. Using Biomod2 software and combining species occurrence and environmental data, a distribution model for C. bimaculata in the southern Bohai Sea is developed. We analyze relationships between this and other crustacean species by comparing niche widths and their overlap. A random forest model outperforms eight others, and has the highest evaluation indices among single algorithm species-distribution models. The evaluation index of an ensemble model is significantly higher than those of single algorithm models, indicating its greater accuracy and robustness. We report suitable habitat for C. bimaculata to occur mainly in central and northeastern Laizhou Bay, and for this habitat suitability to shift over years from the middle to northeastern waters. Niche width showed a negative trend from 2020 to 2022, and is greater in May than August for each year. Niche overlaps between C. bimaculata and other major crustaceans in the southern Bohai Sea exist. We consider that increased sea surface temperature caused by climate change enabled invasion of C. bimaculata from northern Yellow Sea waters into the southern Bohai Sea, where it can overwinter and complete its life cycle. These results provide a scientific basis upon which monitoring of C. bimaculata in the Bohai Sea can be strengthened to better cope with its invasion and any negative impact on local biodiversity.

Background: Epidermal growth factor receptor (EGFR) mutations have been identified as promising therapeutic targets for non-small cell lung cancer. Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor-targeting drug, has good anti-tumor ability and excellent intracranial effects. However, management of osimertinib resistance is a clinical challenge. The clinical benefit of osimertinib combined with the antiangiogenic drug, bevacizumab, remains to be determined. Case presentation: A 40-year-old female with right lung adenocarcinoma (cT2aN3M1c, IVb) was confirmed positive for EGFR exon 19 deletion mutation (c.2235_2249del, 1.3%). After receiving 5 months of osimertinib (80 mg, qd) therapy, the patient's disease progressed and she subsequently accepted treatment with osimertinib (80 mg, qd) plus bevacizumab (15 mg/kg, q21d) and achieved notable clinical remission for 23 months until renal impairment occurred, after which bevacizumab was discontinued. The patient had 6 months of remission before progression, after which bevacizumab was added again. To date, the disease has been under control. The brain lesion showed partial response again, and the side effects of bevacizumab were tolerable. The overall survival time exceeded 4 years. Conclusion: This case report describes a treatment strategy for osimertinib-resistant patients with EGFR exon 19 deletion mutations. Metronomic treatment with osimertinib plus bevacizumab was achieved for more than 4 years.

Abstract In coastal marine sediments, oxygen availability varies greatly, and anoxic conditions can develop quickly over low spatial resolution. Although benthic fungi are important players in the marine carbon cycle, little is known about their adaptation to fluctuating availability of oxygen as terminal electron acceptor. Here, we study which part of a mycobenthic community from oxic coastal sediments can thrive under temporarily anoxic conditions. We test whether phylogeny or certain fungal traits promote plasticity in respect to changes in oxygen availability. Therefore, we incubated mycobenthos under oxic and anoxic conditions, performed ITS2 Illumina tag-sequencing and an additional meta-analysis on a literature survey. Half of all OTUs showed a plasticity towards changing oxygen availability and exhibited different strategies towards anoxic conditions, with rapid response within hours or a delayed one after several days. The strategy of dimorphism and facultative yeasts were significantly linked to OTU occurrence in anoxic conditions, while phylogeny and other traits had less effect. Our results suggest that different fungal niches are formed over the duration of prolonged anoxic conditions. The taxon-specific proliferation seems to be regulated by the fine-tuning of various traits and factors. It is essential to take these results into account when conducting conceptual work on the functionality of the marine benthos.

Abstract Background To compare vitreous angiomosaic images (VAMIs), obtained by widefield swept-source optical coherence tomographic angiography (wfSS-OCTA) and the image of fluorescein fundus angiography (FFA) in the identification of retinal neovascularization (NV) in patients with diabetic retinopathy (DR). Methods In this prospective observational study, severe non-proliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) patients were included. All patients underwent FFA and wfSS-OCTA. The number of NVs identified by wfSS-OCTA VAMIs using five fixations 12 × 12 mm montage scans and the resembling FFA images were compared. Results Fifty-three eyes of 29 patients were enrolled. NVs were detected in 25 eyes by using FFA, including 9 NVs of the disc (NVDs) and 72 NVs elsewhere (NVEs), and in 29 eyes by OCTA, including 11 NVDs and 90 NVEs. The detection rate of NV and NVD of OCTA was comparable to that of FFA (p > 0.05), and the level of agreement was excellent (κ = 0.850, κ = 0.754). Using FFA as the gold standard, the sensitivity for detection of NV by OCTA was 100.0%, specificity was 85.7%, the positive-predictive value was 86.2%, and the negative-predictive value was 100.0%. Compared with FFA, OCTA was superior in terms of the number of NVEs identified (p = 0.024). When we excluded images of patients treated with anti-vascular endothelial growth factor (VEGF) intravitreal therapy for

The Zhangheng-1 electromagnetic satellite is the space-based observation platform of China's stereoscopic earthquake observation system. Its scientific objective is to obtain the global geomagnetic field, electromagnetic field (waves), ionospheric plasma parameters, and high-energy particles for monitoring the dynamic variation of the ionosphere and the seismo-ionospheric disturbances over China and its surrounding areas to compensate for the deficiency of the ground-based observation system. The project explores new ways of earthquake monitoring and prediction by using space science. The first test probe of the Zhangheng-1 electromagnetic satellite series was successfully launched in February 2018, and has been stably operating in orbit for more than four years. The second is an operational probe that will be launched in early 2023. The in-flight commissioning test and cross-calibration work show that the Zhangheng-1 electromagnetic satellite can provide good data quality to support geophysics and space physics studies, and has obtained valuable scientific results in recent years. The global geomagnetic reference model built by Zhenghang-1 data is the first global geomagnetic field model built using only Chinese satellite data, allowing Chinese scientists to take an important role in the computation of the global geomagnetic reference model (IGRF) for the first time in over a century. The ionospheric electron density 3D model based on Zhangheng-1 satellite data can present the ionospheric structure characteristics. In natural hazards monitoring, Zhangheng-1 has shown good response ability to disturbances related to earthquakes, volcano eruptions, and geomagnetic storms. In terms of the lithosphere-atmosphere-ionosphere coupling mechanism study, the full-wave calculation method can provide the electromagnetic field changes between the lithosphere-ionosphere waveguide and the ionospheric wave propagation feature. The results from the full-wave model prove the capability of the Zhangheng-1 satellite's electromagnetic payloads to detect low-frequency electromagnetic emissions induced from the earthquake epicenter. The simulation and observation studies suggest that the Zhangheng-1 satellite can reflect seismic activities, very low frequency (VLF) transmitter, magnetic anomalies in the lithosphere, and lightning activities in the atmosphere. These recent scientific results show that the Zhangheng-1 electromagnetic satellite is consistent with other similar types of electromagnetic satellites worldwide, indicating its great potential in scientific application.

Abstract Predicting SYM‐H index is significant in space weather because it quantifies the degree of perturbation of the geomagnetic field during storm. This study presents a composite model to predict SYM‐H index based on solar wind parameters by combining the empirical magnetospheric dynamical equation with neural networks. The formula for predicted SYM‐H originates from the well‐known empirical relationship between interplanetary conditions and the Dst index. In particular, the coefficients in the empirical relationship are determined by using neural networks that excel at approaching the function linking the coefficients and the solar wind parameters. The 1‐ and 2‐hr forecasts of SYM‐H during storm time are reliable, and the precision of some cases is even better than the latest models solely using deep neural networks. Based on the composite model, the dependence of loss time and injection rates of ring current energy on the solar wind parameters and SYM‐H are investigated.

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.

On May 21, a Ms6.4 earthquake occurred in Yangbi, Yunnan Province. Less than 5 ​h later, on May 21, follows a Ms7.4 earthquake in Madoi, Qinghai Province. In this study, multiple parameters are studied from CSES-01 satellite and GNSS. The parameters include the electron density from LAP, energetic particle flux from HEPP, electric field spectrum from EFD, induced magnetic field spectrum from SCM, and global TEC from ground-based GNSS receivers. In the time scale, all parameters changed on May 15, 17 and 18. The relative amplitude of Ne is more than 200%. In space scale, the clear enhancement focus on the southeast of the epicenter of Madoi, Qinghai, and the shape of the focus region is like a clockwise-30°-rotated rectangle, which is about 45° in length and 20° in width. Moreover, there appeared enhancement in the conjugated region. According to the day-to-day analysis of the low-frequency (75–90 Hz) spectrum of EFD and SCM payloads, the relationship of the increment on May 18 could be confirmed with the successive two earthquakes. The energetic particle fluxes enhanced on May 20. All those changes are located in the east of the following epicenter and appeared just several days before, which could be well explained by the Lithosphere-Atmosphere-Ionosphere theory.

Abstract This paper proposes an adaptive sliding mode control based on an auxiliary distance sensor for nonlinear platoons over vehicular ad‐hoc networks under Denial‐of‐Services (DoS) attacks and external disturbances. DoS attacks can cause packet dropping for the wireless network and will lead to the collision or degradation to adaptive cruise control of platoons. To solve this problem, an adaptive Radial Basis Function (RBF) sliding mode control method is proposed for the attacked platoons. RBF neural networks are used to approximate the unknown nonlinear part and external disturbances contained in the vehicle models. Then the adaptive sliding mode controllers are designed to achieve the control goals: the spacing error converges to zero, and the platoon maintains the string stability. The system's internal stability and string stability are proved. Numerical examples are applied to show the effectiveness of the proposed method. Compared with the existing method, the spacing error is decreased from 5.0726, 6.4637 to 0.0264 for secure distributed adaptive platooning control in PF topology and LPF topology, and the average distance is increased from 7.0580 m, 5.7442 m to 11.8498 m for secure distributed adaptive platooning control in PF topology and LPF topology to maintain a safe distance under the situation of DoS attacks.

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs–without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)–which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

Abstract With the accumulation of data, it is possible to study the long-term variation of Fluxgate Magnetometers (FGM) of High Precision Magnetometer (HPM) onboard the China Seismo-Electromagnetic Satellite (CSES). The calibration method of HPM depends on an assumption that the linear parameters of FGM, including the gain factors, the offsets, and non-orthogonal angles are stable. However, HPM exhibits some unexpected trends in the scalar residuals when processed according to the assumption. Study on the residual finds out that under changing space thermal conditions, the non-orthogonal angles of FGM change periodically, suggesting that the data calibration method we used before should be modified. A multi-dimensional polynomial model is established for defining the change of non-orthogonal angles of FGM as a function of the sun incidence angles, geographic latitude and sensor temperature. Apply the polynomial model to data from August 2018 to May 2021, the standard deviation of the scalar residuals is reduced to around 0.5 nT and tends to be more random and in line with the normal distribution. Meanwhile, the variation trend in gain factors and offset factors are eliminated. Results show that the model can correctly reflect the period variation of the non-orthogonal angles of FGM with the space thermal conditions. Graphical Abstract

As a state-of-the-art distributed learning approach, federated learning has gained much popularity in connected and autonomous vehicles (CAVs). In federated learning, models are trained locally, and only model parameters instead of raw data are exchanged to aggregate a global model. Compared with traditional learning approaches, the enhanced privacy protection and relieved network bandwidth provided by federated learning make it more favorable in CAVs. On the other hand, poisoning attack, which can break the integrity of the trained model by injecting crafted perturbations to the training samples, has become a major threat to deep learning in recent years. It has been shown that the distributed nature of federated learning makes it more vulnerable to poisoning attacks. In view of this situation, the strategies and attacking methods of the adversaries are worth studying. In this paper, two novel optimization-based black-box and clean-label data poisoning attacking methods are proposed. Poisoning perturbations are generated using particle swarm optimization hybrid with simulated annealing and genetic algorithm respectively. The attacking methods are evaluated by experiments conducted on the example of traffic sign recognition system on CAVs, and the results show that the prediction accuracy of the global model is significantly downgraded even with a small portion of poisoned data using the proposed methods.

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing. Diseases are both varied and complex, and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics. Additionally, this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.

The number of vertebrae is a crucial economic trait that can significantly impact the carcass length and meat production in animals. However, our understanding of the quantitative trait loci (QTLs) and candidate genes associated with the vertebral number in sheep (Ovis aries) remains limited. To identify these candidate genes and QTLs, we collected 73 Ujimqin sheep with increased numbers of vertebrae (T13L7, T14L6, and T14L7) and 23 sheep with normal numbers of vertebrae (T13L6). Through high-throughput genome resequencing, we obtained a total of 24,130,801 effective single-nucleotide polymorphisms (SNPs). By conducting a selective-sweep analysis, we discovered that the most significantly selective region was located on chromosome 7. Within this region, we identified several genes, including VRTN, SYNDIG1L, LTBP2, and ABCD4, known to regulate the spinal development and morphology. Further, a genome-wide association study (GWAS) performed on sheep with increased and normal vertebral numbers confirmed that ABCD4 is a candidate gene for determining the number of vertebrae in sheep. Additionally, the most significant SNP on chromosome 7 was identified as a candidate QTL. Moreover, we detected two missense mutations in the ABCD4 gene; one of these mutations (Chr7: 89393414, C > T) at position 22 leads to the conversion of arginine (Arg) to glutamine (Gln), which is expected to negatively affect the protein’s function. Notably, a transcriptome expression profile in mouse embryonic development revealed that ABCD4 is highly expressed during the critical period of vertebral formation (4.5–7.5 days). Our study highlights ABCD4 as a potential major gene influencing the number of vertebrae in Ujimqin sheep, with promising prospects for future genome-assisted breeding improvements in sheep.

Abstract The current understanding of lactate extends from its origins as a byproduct of glycolysis to its role in tumor metabolism, as identified by studies on the Warburg effect. The lactate shuttle hypothesis suggests that lactate plays an important role as a bridging signaling molecule that coordinates signaling among different cells, organs and tissues. Lactylation is a posttranslational modification initially reported by Professor Yingming Zhao’s research group in 2019. Subsequent studies confirmed that lactylation is a vital component of lactate function and is involved in tumor proliferation, neural excitation, inflammation and other biological processes. An indispensable substance for various physiological cellular functions, lactate plays a regulatory role in different aspects of energy metabolism and signal transduction. Therefore, a comprehensive review and summary of lactate is presented to clarify the role of lactate in disease and to provide a reference and direction for future research. This review offers a systematic overview of lactate homeostasis and its roles in physiological and pathological processes, as well as a comprehensive overview of the effects of lactylation in various diseases, particularly inflammation and cancer.

Objective The objective of this study was to analyse the differentially abundant proteins caused by freeze–thawing of ram sperm and explore candidate proteins of interest for their ability to improve ram sperm cryopreservation outcomes in vitro. Methods Sperm were from three mature Dorper. Fresh and frozen sperm proteins were extracted, and the differentially abundant proteins were analysed by mass spectrometry. Among these proteins, lactoferrin (LTF) was selected to be added before cryopreservation. Next, sperm samples were diluted in Tris extender, with the addition of 0, 10, 100, 500, and 1,000 μg/mL of LTF. After thawing, sperm quality was evaluated by motility, plasma membrane integrity, mitochondrial activity and reactive oxygen species (ROS). Results Cryopreservation significantly altered the abundance of 40 proteins; the abundance of 16 proteins was increased, while that of 24 proteins was decreased. Next, LTF was added to Tris extender applied to ram sperm. The results showed that sperm motility and plasma membrane integrity were significantly improved (p0.05). Supplementation of the cryoprotective extender with 10 μg/mL LTF led to decreased ROS levels compared with those in the control and other groups (p

In this study, we aimed to evaluate the efficacy and safety of tacrolimus-based treatment for immunoglobulin A nephropathy (IgAN). We retrospectively reviewed 127 adult patients with primary IgAN with 24 h urine total protein quantity (24 h UTP) ≥ 1 g and serum creatinine ≤3 mg/dL. All patients were divided into tacrolimus (TAC) and control (non-TAC) groups according to the treatment strategy. Proteinuria remission, remission rate, and adverse events were compared between the two groups. Among the 127 patients, 61 received TAC-based treatment and 66 received non-TAC treatment. TAC group exhibited a more rapid decline in proteinuria than the non-TAC group at 3, 9, and 12 months (p = 0.049, 0.001, and 0.018, respectively). Remission rates at 1, 3, 6, 9, and 12 months were 41.0, 68.9, 80.3, 90.2, and 88.5%, respectively, in the TAC group. These rates were higher than those in the control group at 3, 9, and 12 months (p = 0.030, 0.008, and 0.026, respectively). Complete remission rates at 1, 3, 6, 9, and 12 months were 6.56, 19.7, 37.7, 54.1, and 62.3%, respectively, in the TAC group. These rates were higher than those in the control group at 9 and 12 months (p = 0.013 and 0.008, respectively). The estimated mean time to complete remission was significantly shorter in the TAC group than in the control group (p = 0.028). TAC did not increase the incidence of adverse events. In conclusion, TAC accelerated proteinuria remission in patients with non-rapidly progressive IgAN with no increased risk of adverse events. Further prospective randomized controlled trials are necessary to validate our findings.

Herein, we investigated the synergistic degradation of p-chlorophenol by a Ag3PO4/Fe3O4/graphene oxide visible light–peroxydisulfate coupled system, probed the effects of catalyst and peroxydisulfate dosage, pH, operating mode, and coexisting substances, identified decomposition intermediates, and proposed plausible degradation pathways. The advantages of the coupled system, namely reduced agent dosage and efficient and thorough degradation, justified the involvement of a precious metal (Ag), while mechanistic investigations suggested the importance of the peroxydisulfate peroxo bond and electron transfer between multivalent metal catalyst components for degradation performance enhancement. Thus, this work facilitates the development of high-efficiency and low-cost combinations of advanced oxidation processes.

This study aimed to evaluate the suppressive potential of different soils on soybean cyst nematodes (SCN) and to estimate the suppressive mechanism. Fifteen soils (designated as soil A to O) from different agricultural fields with varying organic inputs were added with SCN-infested soil and grown with a green soybean variety. The SCN density in the soil at 6 weeks of soybean growth was markedly different depending on the soils used, indicating a different level of disease suppressiveness. No significant correlation was observed between the SCN density and any of the soil physicochemical and biological characteristics tested. Then, to estimate a suppression mechanism, F-soil that showed the lowest density of SCN was added to the SCN-infested soil with or without streptomycin to kill bacteria and grown with soybean. SCN density was not increased by the addition of streptomycin, indicating that soil bacteria may not be involved in the suppressiveness of F-soil. In total, 128 fungal strains were isolated from the rhizosphere of F-soil and inoculated in a combination or singly in the SCN-infested soil. After repeated screenings, five strains were selected since the SCN density was consistently decreased by them. Sequence analysis showed that they were closest to Clonostachys rosea, Aspergillus niger, Aspergillus fumigatus, Fusarium oxysporum, and Cylindrodendrum alicantinum. All five strains significantly reduced the mobility of second-stage juveniles (J2). Further, C. rosea a2, A. niger a8, and F. oxysporum a25 significantly decreased hatching. Overall, the present study demonstrated that soil fungi played an important role in SCN suppression in F-soil.

Ewes undergo complex metabolic changes during pregnancy. Understanding the specific process of these changes is a necessary prerequisite in ewes for regulating and intervening in order to maintain pregnancies. However, there have been relatively few studies on the specific changes that occur in nutritional metabolism in pregnant ewes during early gestation, especially for some landrace ewes in highly cold areas. Therefore, this study aimed to (1) elucidate the changes in metabolites and microbial communities in pregnant ewes during early gestation using metabolomics and 16S ribosomal RNA gene (rDNA) amplicon sequencing approaches, and to (2) discover novel early pregnancy-induced biomarkers in the blood and faeces. Rams were placed together with ewes on D0 and removed on D45. During early gestation, blood and faecal samples were collected from ewes in a highly cold area for analysing the metabolites and microbial communities; these were retrospectively classified as the early gestation pregnant (EP) ewe group or the nonpregnant (NP) ewe group based on the lambing status recorded during the expected delivery period. The differences in the plasma biochemical parameters, plasma metabolites, and faecal microbial communities of pregnant and nonpregnant ewes were characterised. The GC, IL-6, O-acetyl-l-serine, L-glutamine, and 6-acetamido-2-oxohexanoic acid were screened out as potential biomarkers for evaluating the occurrence of early pregnancy. These novel early pregnancy-induced metabolites discovered in ewes might allow for the development of technologies to detect early pregnancies in sheep in highly cold areas.

Abstract Background Missense mutations in the mitochondrial alanyl-tRNA synthetase 2 (AARS2) gene are clinically associated with infantile mitochondrial cardiomyopathy or adult-onset leukoencephalopathy with early ovarian failure. To date, approximately 40 cases have been reported related to AARS2 mutations, while its genetic and phenotypic spectrum remains to be defined. Case presentation We identified a 24-year-old Chinese female patient with adult-onset leukoencephalopathy carrying novel compound heterozygous pathogenic mutations in the AARS2 gene (c.718C > T and c.1040 + 1G > A) using a whole-exome sequencing approach. Conclusions Our findings further extend the mutational spectrum of AARS2-related leukoencephalopathy and highlight the importance of the whole-exome sequencing in precisely diagnosing adult-onset leukoencephalopathies.

Background: Although ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. Methods: The ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E2 (PGE2) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. Results: HPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. Conclusion: RGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

Abstract The medical application of chitosan (Cs) has been for about half a century, but the molecular mechanism has not been elucidated yet. This study is to explore the antibacterial mechanism of chitosan nanoparticles (Csnp) in dentin at the atomic resolution level. Extracted tooth specimen was prepared in three groups: A. control group; B. Csnp treatment under ultrasonic agitation (UA); C. Csnp treatment without UA. A scanning electron microscope (SEM) was used to observe the Csnp distribution on the dentin surface. The incubations of Enterococcus faecalis (E. faecalis) were performed. Further, we explored the protection mechanism of chitosan polymers to collagen type I, using molecular docking technique and crystal structure superimposition analysis. We revealed that Csnp under UA was evenly distributed on the dental surface and the Csnp-pretreated dentin had great antibacterial activity for E. faecalis. Our work demonstrated that Csnp occupied the grooves of the triple-helical collagen surface, strengthened by crosslinking, and interfered with the bond of collagen adhesin through steric hindrance effect and interrupting hydrophobic interaction. Csnp protects dentin against E. faecalis by interacting and crosslinking with collagen type I and prevents bacterial collagen adhesin binding through steric hindrance effect and interrupting hydrophobic interaction. Graphical abstract

Automated driving technology is one of the emerging technologies which will change the transportation mode in the future. Distributing the automated driving vehicles from the automobile factory to dealers has a huge difference compared with traditional vehicles. This paper considers the variety of cases where the automated driving vehicles can be both distribution tools and distribution goods. Then establishes a new distribution model that integrates self-distribution of autonomous vehicles into the existing distribution rings form a complex network composed of ring-branches. This cooperative distribution model of automated driving and traditional vehicle transport to minimize transportation cost and maximize the overall efficiency. Furthermore, we design an improved adaptive large neighborhood algorithm (ALNS) to solve the model which combines the merger heuristics and splitter heuristics to promote generate the optimal solutions. The efficiency of our proposed method is proved by real-world data from an automobile enterprise. Additionally, the sensitivity analysis of the maximum distance for automated driving vehicles to be delivered by themselves suggests that the larger distance, the more outstanding of cost reduction and efficiency increase for our proposed model.

Abstract Background Falls are a common and serious public health issue among older adults, contributing to the loss of independence, psychological distress, and incapability to engage in meaningful occupations, etc. However, there is a lack of abundant information about the fall risk self-evaluation scale for community-dwelling older people. Therefore, this study aimed to evaluate the preliminary reliability and validity of the fall risk self-assessment scale (FRSAS) among community-dwelling older adults. Methods A cross-sectional study was conducted. A total of 230 individuals aged 65 years and over were recruited by a convenience sampling between October and December 2020 from three communities in Haidian district, Beijing. Eligible participants were required to fill in the general condition questionnaire and the fall risk self-assessment scale. The reliability and validity were analyzed by using SPSS 20.0. Results Two hundred twenty-two participants completed the assessment as required (the completion rate was 96.52%). The most items of FRSAS were understood by older adults, which was completed in 10 min. Cronbach’s α and intraclass correlation coefficient ICC (2,1) of the scale were 0.757 and 0.967 respectively, suggesting good internal consistency and test-retest reliability. Exploratory factor analysis yielded 14 factors that explained 61.744% of the variance. Five items failed to be categorized into any factors because the factor loading of these items was less than 0.4. A future large-sample study needs to be conducted to explore its construct validity. The total scores and dimensional scores except for C-dimension showed significant differences between participants who had experienced a fall in the previous 6 months and those who had not (P

IntroductionOnion (Allium cepa L., 2n=16) is an economically and nutritionally important vegetable crop worldwide. Construction of a high-resolution genetic map and map-based gene mining in onion have lagged behind other vegetable crops such as tomato and pepper.MethodsIn this study, we constructed a high-resolution genetic map of onion using 321 F2 individuals from a cross between two double haploid lines DH-1×DH-17 and employing specific length amplified fragment (SLAF)-seq technology. The genetic map containing 10,584 polymorphic SLAFs with 21,250 single nucleotide polymorphism (SNP) markers and 8 linkage groups was developed for onion, which spanned 928.32 cM, with an average distance of 0.09 cM between adjacent markers.ResultsUsing this map, we carried out QTL mapping of Ms locus related to the male-fertile trait and reproduced previous mapping results, which proved that this map was of good quality. Then, four QTLs (located on LG2, LG5, and LG8) were detected for flower stalk height, explaining 26.60% of the phenotypic variance. Among them, we proposed that 20 SLAF markers (in three QTLs) of flower stalk height trait were effective favorable allelic variant markers associated with heterosis.DiscussionOverall, the genetic map was structured using SLAF-seq based on DH lines, and it is the highest-quality and highest-resolution linkage map of onion to date. It lays a foundation for the fine mapping and candidate gene identification of flower stalk height, and provides new insights into the developmental genetic mechanisms in onion breeding.

A one-pot two-step reaction of 2-(trifluoromethyl)-2-hydroxy-2H-chromene with aryl ketone afforded α-trifluoromethylated tertiary alcohols bearing coumarins. The atomic economic and simply manipulative reaction involved premier treatment of reaction mixtures with CH3COOH and NH4OAc in one-pot process. The reaction proceeded to give the title compounds in moderate to good yields.

Abstracts: This work analyzed the electromagnetic field (EM) anomalies recorded by the electric field detector (EFD) and the search coil magnetometer (SCM) onboard the China Seismo-Electromagnetic Satellite (CSES) during the two earthquakes (EQ), which are the Yangbi Ms6.4 EQ on May 21 (China Standard Time, CST) and the Madoi Ms7.4 EQ on May 22 (CST), 2021. These two EQs successively occurred in West China. The prevailing frequency band excluding the interferences from the satellite platform was chosen to extract convincible seismic-related EM disturbances. Two criteria were put forward to obtain reliable precursors using the Kp and Dst index and the variation rate of Dst per hour to eliminate the tinier spatial perturbations. We found that the seismic-related EM disturbances mainly appeared 1–10 days before the two earthquakes within the spatial extension of 1000 ​km above the epicenters.