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Abstract The small genera Allaeanthus and Malaisia within the Moraceae have important edible, medicinal, and economic value. However, complete plastome blueprints and a well-resolved evolutionary history of these two genera are still lack, thereby limiting their conservation and application. The recent discovery of a new distribution of Allaeanthus kurzii in Hainan, China, marked by the collection of two unique samples, alongside three samples of Malaisia scandens, has opened new avenues for research. This study aimed to compare the Allaeanthus and Malaisia plastomes of Hainan Province samples with those of samples from other regions, focusing on plastome structure, codon usage bias, natural selection, and the evolutionary history of A. kurzii and M. scandens. The results showed that both species had a quadripartite plastome structure, with sizes ranging from 162,134 to 162,170 bp for A. kurzii and 161,235 to 162,134 bp for M. scandens. Both species displayed loss of the infA gene and reduction of the rpl22 gene. Two highly variable regions (petD-trnD-GUC and rpl20-clpP) and three highly variable genes (rpl20, petB, and rpl16) were identified in A. kurzii, while two highly variable regions (ycf2-ndhB and ccsA-ndhE) and three highly variable genes (psbT, rpl36, and ycf2) were found in M. scandens. The protein-coding sequences (CDSs) of the Allaeanthus and Malaisia plastomes exhibited similar patterns of adaptive indices and codon usage frequencies. The genes associated with photosynthesis underwent strong purifying selection. Phylogenetic analysis revealed that Allaeanthus, Broussonetia, and Malaisia constituted a monophyletic group, with Malaisia being more closely related to Broussonetia. Broussonetia diversified approximately 19.78 million years ago, Malaisia approximately 4.74 million years ago, and Allaeanthus approximately 16.18 million years ago. These new plastome-based discoveries will guide conservation planners and medicinal plant breeders and genetic resource development for these species in the region.

Abstract Exploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth.

Abstract Background The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. Methods A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. Results During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p

Autoclave corrosion testing has been used for many years; however, few have studied the effect of its shortcomings on the formation of corrosion products and corrosion behaviour. In particular, understanding of these effects under high temperature and high pressure (HTHP) is rare. In this study, we highlighted the important parameters such as heating periods, flow rates and volume-to-surface ratios influencing carbon steel corrosion in the early stages. Especially, characterisation and protection behaviour of corrosion products associated with corrosion behaviour in the heating stage under the geothermal CO2-containing environment were systematically studied via mass loss, in-situ electrochemistry and surface analysis techniques. The roles of pCO2, volume-to-surface ratio and flow rate influence the formation of the corrosion products in the early stage are also evaluated.

Abstract Background Engelhardia (Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of Engelhardia, the maternal genome evolution and phylogeny of Engelhardia in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight Engelhardia species and the outgroup Rhoiptelea chiliantha, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of Engelhardia and the whole Juglandaceae family. Results The 13 Engelhardia plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (TrnK-rps16, ndhF-rpl32, and ycf1) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only rpl22 and psaI genes showed positive selection (Ka/Ks > 1). Phylogenetic results fully supported Engelhardia as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The Engelhardia originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn’t support rapid radiation occurred in the evolution history of Engelhardia. Conclusion Our study fully supported the taxonomic treatment of at the section for Engelhardia species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of Engelhardia and the whole Juglandaceae family.

Flood frequency in river source regions is significantly affected by rainfall and snowmelt as part of climatic changes. A traditional univariate flood frequency analysis cannot reflect the complexity of floods, and when used in isolation, it can only underestimate flood risk. For effective flood prevention and mitigation, it is essential to consider the combined effects of precipitation and snowmelt. Copula functions can effectively quantify the joint distribution relationship between floods and their associated variables without restrictions on their distribution characteristics. This study uses copula functions to consider a multivariate probability distribution model of flood peak flow (Q) with cumulative snowmelt (CSm) and cumulative precipitation (CPr) for the Hutubi River basin located in northern Xinjiang, China. The joint frequencies of rainfall and snowmelt floods are predicted using copula models based on the Coupled Model Intercomparison Project Phase 6 data. The results show that Q has a significant positive correlation with 24-d CSm (r = 0.559, p = 0.002) and 23-d CPr (r = 0.965, p

In order to distinguish terrestrial material sources in the Okinawa Trough (OT), this study analyzed four surface sediment samples from the northern, middle, and southern parts of the OT using detrital zircon U-Pb age analysis. The detrital zircon age distributions in the northern Okinawa Trough (N-OT) predominantly fall into 1,000−2,300 Ma and 100−600 Ma age groups. In contrast, in the middle Okinawa Trough (M-OT) and southern Okinawa Trough (S-OT), the detrital zircon age groups of 100−600 Ma and 600–1,000 Ma increase significantly, while the age groups of 1,000−2,300 Ma and >2,300 Ma decrease. Detrital zircons from the N-OT primarily originate from the Yellow River and mixed with the Old Yellow River, while those from the M-OT come mainly from the Yellow River, Yangtze Rivers, and East China Sea. And Zhuoshui River maybe a potential source for the M-OT. The detrital zircons from the S-OT are mainly influenced by the Yangtze River, with some effects from the Lanyang River. This study utilizes detrital zircon U-Pb age analysis to gain a better understanding of the terrestrial material sources in various regions of the OT. Most of the zircon grain are coarse, with grain sizes of 40–150 μm long and 30–100 μm wide in the N-OT, smaller in the M-OT and S-OT in this study, which are probably not modern deposits, but the products in the low sea level period of last glaciation mixed with modern sediments. The transport and sedimentation processes reflect the comprehensive influence of sea level change, Kuroshio Current, river input, East Asian monsoon and other factors from last glaciation to present.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress β-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Leveraging a fresh comprehension of electrolytic polishing (EP) mechanisms, this study introduces a pivotal factor - viscosity/water content ratio (VWR) - for the first time, rooted in acidity ratio theory. The present study aligns with published works to affirm the validity of the VWR indicator and its correlation with surface roughness. A noteworthy contribution lies in the design of EP solutions that can serve as a guide for stainless steels. It strikes a balance between low cost, high efficiency, long service life and desirable surface roughness. This involves regulating the dissolution-ionization-deposition process at the metal/solution interface.

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

Lewis base additives typically undergo interactions with SnI2 to achieve effective defect passivation in lead-free perovskite films. In this work, the thiophene ring in 2-thiophenethylammonium chloride (TEACl) has coordination interactions with Sn2+ and the -NH3+ therein forms hydrogen bonds with I-. This facilitates the deposition of homogeneous and dense films with fewer defects during crystallization process. Otherwise, 2-pyridinethylammonium chloride (AEPCl) gives poorly perovskite films with high defect density because of the overly strong interaction with SnI2. As a result, the average photoluminescence life time of TEACl-passivated perovskite film was substantially increased to 22.04 ns, compared with the control film (5.15 ns) and the AEPCl-passivated film (3.55 ns). Ultimately, the target solar cell with TEACl passivation presented a power conversion efficiency of 13.24% and excellent shelf-stand stability with a 90% retaining of initial efficiency after 2000 h of aging in N2 atmosphere. This work sheds new light on the structural tailoring of Lewis base passivators for efficient defect passivation in lead-free tin halide perovskites.

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ.

Abstract Background Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. Methods In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. Results Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. Conclusion Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

Abstract Background COVID-19 is continuing to ravage globally and has resulted in a huge health and financial burden. Chinese proprietary medicines, such as Lianhua Qingwen (LHQW) and Huoxiang Zhengqi (HXZQ) capsules, have been recommended for non-high-risk patients with COVID-19 in China. Based on this, we described the baseline information, using status of LHQW and HXZQ capsules and inoculation history of quarantined patients in the second half of 2022 in Macao. Additionally, we analyzed the underlying association among medicines administration, vaccination and COVID-19 indices, in order to explore novel clues for the regular control and prevention of local epidemic situation in the future. Methods A total of 976 patients in Macao quarantine hotels from June to August 2022 were included in the present study, of which, 857 subjects were followed-up for prognosis evaluation. During quarantine, the baseline demographic information, including sex, age, BMI, occupation and personal habits were collected. Additionally, the inoculation history, medicine employment status and cycle threshold (Ct) values were also reported. We interviewed the patients for collection of their symptoms at the beginning and end of quarantine, as well as prognostic ones. Basic statistical description of baseline information, vaccination history and medication were displayed. Chi-squared test or with continuous correction test was employed for comparison of dichotomous data between two or multiple groups. Binary logistic regression was applied to reveal the correlation between potential risk factors and Ct values or prognosis symptoms. We also used Cox regression model to identify the effect of different types of vaccine products on Ct value altering rate. Results Patients who were female (52.0%), engaged in service industry (31.8%), from Macao native (65.8%), never took physical exercises (33.6%) and preferred irritated diet (59.5%) enjoyed more dominant proportions. Over 80% of participants were inoculated and 74.6% of them chose inactivated COVID-19 vaccine produced by China National Biotech Group (CNBG). Participants used LHQW capsules accounted for 92.1% and the duration of medicating lasted for one to two weeks. All of the reported symptoms were significantly ameliorated after quarantine and the duration of quarantine was concentrated on 21 days. People with different age, sex, occupation and region had different choices of HXZQ administration and vaccination. Additionally, middle dose (4–5 boxes) of LHQW capsules exhibited evidently negative association with positive Ct values (adjusted, − 0.037 ± 0.19, p = 0.04). Two doses of CNBG and one dose of mRNA vaccine had obvious protective effect on reducing Ct positive rate (p = 0.041). Meanwhile, symptoms after quarantine were significantly positive correlated with those in prognosis (adjusted, 1.38 ± 0.18, p