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Abstract The effects of dams on carbon dioxide (CO2) fluxes in downstream lakes remain elusive. Here we combined eddy covariance observations and random forest models to examine multi‐decadal variations in CO2 fluxes in the Poyang Lake, the largest freshwater lake in China, and quantified the contribution of the Three Gorges Dam (TGD), the world's largest hydraulic project. We found the lake fluctuated between CO2 source and sink in 1961–2016, and tended to be CO2 sink in the post‐TGD period (2003–2016) when vegetation expanded early and spatially due to declining water level. TGD can explain approximately 6% of the total differences in annual CO2 fluxes, with major contributions in the impoundment period (up to 22% in middle September to October). The results show a positive side of operational major hydraulic projects on lake carbon sink, and probably caution the negative side of carbon release after dam removal.

Numerous floodplain lakes in the world have been shrinking and gradually transformed into semi-closed reservoirs under the control of sluices for the past century, which has led to substantial ecosystem services loss. In this study, historical topographic maps 1930s and 1970s and remote sensing images (1980s–2020s) are used to reconstruct the centennial evolution characteristics of typical lakes in the Central Yangtze Ecoregion, i.e., the Wanjiang lake group. Moreover, we focus on their driving factors from the perspective of sluice control and agricultural activities. Results showed that the lake wetland area in the Wanjiang Plain shrank remarkably in the 1930s–2020s, with an overall loss rate of 45.32 %, of which 84.19 % was mainly in the 1930s–1970s. The wetland loss was accompanied by the dispersion of large lakes, the extinction and newbirth of small lakes. The uneven distribution of the wetland loss in space led to the overall migration of the lakes to the Yangtze River. These results can be explained as follows: from the 1950s to the 1970s, sluices were built on waterways between 91.67 % of lakes and the Yangtze River for flood mitigation. The flood risk control further led to the surge of building state-owned farms and personal polders in the local area from the 1950s to the 1980s, which was the primary cause for the loss of lake wetlands and the regularization of lake shorelines. Since the 1980s, lake protection measures have promoted the restoration of wetlands and reduced the rate of lake shrinkage to a certain extent. Our findings can provide important guidance for the sustainable management and possible hydrological connectivity restoration project in the middle and lower reaches of the Yangtze River.

Investigating the contributions of the factors influencing lake water level and their related changes with regard to hydraulic facilities is vital for understanding the driving mechanism of water level variations under the manifold pressures from anthropogenic activities and climate change. In this study, a random forest (RF) model was used to investigate the changes of the relationship between water level and discharge of the Yangtze River and local tributaries in Poyang Lake, China, based on daily hydrological data from 1980 to 2018. The results indicated that RF exhibited robust capability for water level prediction in Poyang Lake, with average R2 of 0.95, 0.88, 0.92, and 0.94 for the dry, rising, wet, and recession seasons, respectively. Predictor importance analysis showed that the discharge of the Yangtze River had greater influence on the water level than the discharge of local tributaries except for the dry season in Poyang Lake, where the influence on the water level was evident with discharge less than 5,000 m3/s. The influence of the Yangtze River also showed a clear attenuation pattern as the distance from the outlet of the lake increased, where the water level was constantly regulated by the Yangtze River. In addition, the partial dependence plots also indicated that the Yangtze River discharge changes after the TGD operation have resulted in remarkable water level decreases in the wet and recession seasons, especially for the recession period. Meanwhile, a slight increase in water level was predicted under identical discharge of local catchment in the dry season, which was only concentrated in the outlet of the lake. This study indicated the RF model as a robust technique for water level predictions and attribution analysis under multiple temporal and spatial scales. Moreover, this study confirmed the uneven influences of the Yangtze River and local tributaries on water level across different seasons, gauging stations, and phases.

Flooding is an important factor influencing the biomass production of vegetation in natural wetland ecosystems. However, how biomass production is linked to flooding patterns in wetland areas remains unclear. We utilized gauging station data, a digital elevation model, vegetation survey data, and a Landsat 8 image to study the effects of average inundation depth (AID) and inundation duration (IDU) of flooding on end-of-season biomass of vegetation in Poyang Lake wetland, in particular, after operation of Three Gorges Dam. The end-of-season biomass of wetland vegetation showed Gaussian distributions along both the AID and IDU gradients. The most favorable flooding conditions for biomass production of vegetation in the wetland had an AID ranging from 3.9 to 4.0 m and an IDU ranging from 39% to 41%. For sites with a lower AID ( 41%), the end-of-season biomass values were negatively related. After the operation of the Three Gorges Dam, flooding patterns characterized by AID and IDU of the Poyang Lake wetland were significantly alleviated, resulting in a mixed changing trend of vegetation biomass across the wetland. Compared with 1980–2002, the increase of end-of-season biomass in lower surfaces caused by the alleviated flooding pattern far exceeded the decrease of end-of-season biomass in higher surfaces, resulting in an end-of-season biomass increase of 1.0%–6.7% since 2003. These results improved our understanding of the production trends of vegetation in the wetland and provided additional scientific guidance for vegetation restoration and wetland management in similar wetlands.

Wetland biomass is an important indicator of wetland ecosystem health. In this study, four dominant vegetation communities (Carex cinerascens, Phalaris arundinacea, Artemisia selengensis, and Miscanthus sacchariflorus) in the Poyang Lake wetland from 2010 to 2016 were classified from Landsat images using spectral information divergence (SID). We combined aboveground biomass (AGB) field measurements and remote sensing data to establish a suitable model for estimating wetland AGB in Poyang Lake, which is on the Ramsar Convention’s list of Wetlands of International Importance. The results showed that (1) overall, the classification accuracy for vegetation pixels across 5 years ranged from 59.1% to 73.7% and (2) the inter-annual and spatial variations in the AGB of the four vegetation types were clear. C. cinerascens had an average AGB density value of 1.28 kg m−2 in Poyang Lake from 2010 to 2016; M. sacchariflorus had the highest AGB density with an average value of 1.39 kg m−2; A. selengensis had almost the same level at 1.26 kg m−2; and P. arundinacea had the lowest AGB density at 0.64 kg m−2. This study provides useful experience for estimating carbon sequestration of vegetation in freshwater wetlands.

Quantitatively mapping forest aboveground biomass (AGB) is of great significance for the study of terrestrial carbon storage and global carbon cycles, and remote sensing-based data are a valuable source of estimating forest AGB. In this study, we evaluated the potential of machine learning algorithms (MLAs) by integrating Gaofen-1 (GF1) images, Sentinel-1 (S1) images, and topographic data for AGB estimation in the Dabie Mountain region, China. Variables extracted from GF1 and S1 images and digital elevation model data from sample plots were used to explain the field AGB value variations. The prediction capability of stepwise multiple regression and three MLAs, i.e., support vector machine (SVM), random forest (RF), and backpropagation neural network were compared. The results showed that the RF model achieved the highest prediction accuracy (R2 = 0.70, RMSE = 16.26 t/ha), followed by the SVM model (R2 = 0.66, RMSE = 18.03 t/ha) for the testing datasets. Some variables extracted from the GF1 images (e.g., normalized differential vegetation index, band 1-blue, the mean texture feature of band 3-red with windows of 3 × 3), S1 images (e.g., vertical transmit-horizontal receive and vertical transmit-vertical receive backscatter coefficient), and altitude had strong correlations with field AGB values (p < 0.01). Among the explanatory variables in MLAs, variables extracted from GF1 made a greater contribution to estimating forest AGB than those derived from S1 images. These results indicate the potential of the RF model for evaluating forest AGB by combining GF1 and S1, and that it could provide a reference for biomass estimation using multi-source images.

Poyang Lake is an important wetland with international significance in biodiversity conservation and local carbon cycle. A study was conducted to investigate the effects of vegetation communities on seasonal and spatial variations of soil organic carbon (SOC) and dissolved organic carbon (DOC) in two dominant wetlands (dish-shaped pit wetland and delta wetland) of Poyang Lake, China. Results revealed significant variations of SOC and DOC along the vegetation gradient. Maximum accumulation of SOC and DOC was produced in Phragmites community, and the minimum ones in Phalaris community both in spring and in autumn. In comparison with delta wetland, dish-shaped pit wetland obtained higher SOC within the same vegetation type, which indicated that soils of dish-shaped pit wetland had greater capacity to store carbon. Compared with SOC, DOC represented stronger seasonal variations with great increase in autumn, which suggested that DOC was more sensitive to hydrology processing. Furthermore, significant variations of SOC and DOC were closely related to vegetation biomass both in spring and in autumn. Moreover, elevation and gradient also affected the distributing pattern of organic carbon suggesting significant influence of topography characteristics on the carbon pool.

Modeling of hydrological time series is essential for sustainable development and management of lake water resources. This study aims to develop an efficient model for forecasting lake water level variations, exemplified by the Poyang Lake (China) case study. A random forests (RF) model was first applied and compared with artificial neural networks, support vector regression, and a linear model. Three scenarios were adopted to investigate the effect of time lag and previous water levels as model inputs for real-time forecasting. Variable importance was then analyzed to evaluate the influence of each predictor for water level variations. Results indicated that the RF model exhibits the best performance for daily forecasting in terms of root mean square error (RMSE) and coefficient of determination (R2). Moreover, the highest accuracy was achieved using discharge series at 4-day-ahead and the average water level over the previous week as model inputs, with an average RMSE of 0.25 m for five stations within the lake. In addition, the previous water level was the most efficient predictor for water level forecasting, followed by discharge from the Yangtze River. Based on the performance of the soft computing methods, RF can be calibrated to provide information or simulation scenarios for water management and decision-making.

The Jingjiang Three Outlets (JTO) are the water-sediment connecting channels between the Yangtze River and the Dongting Lake. The discharge diversion of the JTO plays a dominant role in the flood control of the middle–lower Yangtze River, Dongting Lake evolution, and ecological environment. After the operation of the Three Gorges Dam (TGD), the river channels downstream experienced dramatic channel changes. To study the influences of the channel change on the discharge diversion, the authors analyzed the channel changes by water level–discharge rating curves and cross-sectional channel profiles in 1980–2014. Hence, changes in the water level with the same discharge and the decline of discharge diversion at the JTO were noted. Channel incision caused the water level with the same discharge to greatly decrease in the upper Jingjiang River. The water level with the same discharge significantly increased at the JTO as a result of the channel deposition. The channel changes contributed approximately 37.74% and 76.36%, respectively, to the amount and ratio of discharge diversion decreases after the TGD operation. The channel changes serve as the primary factor in facilitating the decrease in the discharge diversion ratio, but not the main factor for the decreased amount of the discharge diversion.

Water and mass exchange between rivers and lakes are key processes that maintain the health of the ecology of river–lake systems. Alteration to river–lake interactions have great impacts on water and mass balances. Naturally connected to the middle Yangtze River are the Poyang Lake and Dongting Lake, which are the largest and the second largest freshwater lakes in China. The operation of the Three Gorges Dam (TGD) in the upper Yangtze River was found to have substantial impacts on the middle Yangtze river–lake system. In the past decade, unusual seasonal dryness was evident in the two lakes. Considerable deviations in lake water quality and wetland ecosystem were also detected. In order to explore and distinguish the causal factors influencing the river–lake system, the Ministry of Sciences and Technology (China) launched a research project in 2012, the National Basic Research Program of China (973 Program) (2012CB417000). This article provides an overview of advances in this research, including the evolution of the river–lake interactions, the impacts of the TGD, and the influences on lake hydrology, water quality, and ecosystem. The 20 papers in this issue deliver part of the research outcomes of this project.

Freshwater lakes encounter a series of problems, such as a decline in lake water quality, a sharp decrease in biodiversity, and ecological degradation. As such, lacustrine studies by highly skilled professionals and managers with water resources at home and abroad have focused on assessing the aquatic ecosystem health status of lakes. In this study, the health status of the aquatic ecosystem in the largest freshwater lake in China (Poyang Lake) was assessed, and its temporal and spatial characteristics were illustrated. The index contained three element layers, including hydrologic characteristics, trophic status, and aquatic organisms. The health status of the aquatic ecosystem was classified into three categories: ‘good’, ‘moderate’ (subhealthy), and ‘bad’. It was examined through extension evaluation method. Results showed ‘moderate’ health status, whereas remarkable seasonal and spatially variations. The annual changes in the health status were remarkably due to the influence of complex hydrological and hydrodynamic conditions. This study provides an overall understanding of the aquatic ecosystem evaluation in Poyang Lake. Such an understanding is vital for environmental conservation and identification of causes of the aquatic ecosystem degradation in Poyang Lake.

The carbon sequestration capacity of wetland vegetation determines carbon stocks and changes in wetlands. However, modeling vegetation carbon sequestration of herbaceous wetlands is still problematic due to complex hydroecological processes and rapidly changing biomass carbon stocks. Theoretically, a vegetation index (VI) time series can retrieve the dynamic of biomass carbon stocks and could be used to calculate the cumulative composite of biomass carbon stocks during a given interval, i.e., vegetation carbon sequestration. Hence, we explored the potential for mapping vegetation carbon sequestration in herbaceous wetlands in this study by using a combination of remotely sensed VI time series and field observation data. This method was exemplarily applied for Poyang Lake wetland in 2016 by using a 16-day Moderate Resolution Imaging Spectroradiometer (MODIS) enhanced vegetation index (EVI) time series. Results show that the vegetation carbon sequestration in this area was in the range of 193–1221 g C m−2 year−1 with a mean of 401 g C m−2 year−1 and a standard deviation of 172 g C m−2 year−1 in 2016. The approach has wider spatial applicability in wetlands than the currently used global map of vegetation production (MOD17A3) because our carbon estimation in areas depicted by ‘no data’ in the MOD17A3 product is considerable, which accounts for 91.2–91.5% of the total vegetation carbon sequestration of the wetland. Thus, we determined that VI time series data shows great potential for estimating vegetation carbon sequestration in herbaceous wetlands, especially with the continuously improving quality and frequency of satellite VI images.

A pin-on-disk friction and wear tester was used to investigate the tribological properties of multi-walled carbon nanotubes with different sizes and volume fractions as LB2000 vegetable-based oil additive. The wear scar of disk was characterized using scanning electron microscopy and Raman spectroscopy. Furthermore, the lubrication mechanism of multi-walled carbon nanotubes as vegetable-based oil additive was also discussed. It was found that thin and short multi-walled carbon nanotubes could improve the friction-reducing and anti-wear properties of vegetable-based oil more effectively than thick and long multi-walled carbon nanotubes. The optimal volume fraction of thin and short multi-walled carbon nanotubes was found to be 0.05%.

In this article, the electrostatic atomization experimental setup was designed and fabricated, and high-speed camera was used to observe and analyze the atomization modes of graphite water-based and oil-based nanofluid using cutting tool as electrode under different electrode voltages and distances, flow rates, and nozzle angles. Three-dimensional finite element simulations of the electrostatic field between nozzle and cutting tool were conducted using the software Ansoft Maxwell to investigate the effect of electrode voltage and nozzle angle on the electrostatic atomization mode. The results indicate that spindle mode is a suitable electrostatic atomization mode for cooling and lubricating the cutting edge. The nozzle angle with the largest electrostatic field intensity is presented so as to generate good break-up effect of jet in spindle mode. Furthermore, the operating range of spindle mode in terms of the electrode voltage and flow rate for graphite water-based and graphite oil-based nanofluid under the nozzle angle with the largest electrostatic field intensity is achieved. The outcome of this study is helpful for further development of electrostatic atomization cutting technique.

Determining the spatiotemporal water quality patterns and their corresponding driving factors is crucial for lake water quality managements. This study analyzed hydrological data and concentrations of 11 water quality parameters, including total nitrogen, total phosphorus, ammonia nitrogen and chlorophyll–a (Chl–a), for water samples collected from 15 sampling sites between 2009 and 2014. The water quality of sites in the northern Poyang Lake–Yangtze River waterway was influenced by different environmental parameters compared to sites in central lake, especially for Chl–a concentration. All pollutant parameters were significantly higher in the river phase (water level 14 m) (p < 0.05). These results were confirmed via principal component analysis, which identified three principal components that explained over 79% of the dataset variance. Among all the parameters related to climatic factors, eutrophication and organic pollution were the most important contributors in water quality. Dilution was the controlling factor that drove the seasonal variability in the water quality of the Poyang Lake, China. This work further indicated that regulating pollutant effluents in tributaries and water level within the lake could improve the water quality in Poyang Lake, which may give some impetus for water quality management.

Abstract Background Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. Results Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. Conclusions The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.

Abstract Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.

Background: Exosomes, one of small extracellular vesicles, play a vital role in cell to cell communication and contribute to the advancement of tumors through their cargo molecules. Exosomal circRNAs have emerged as significant players in various types of tumors. Thus, this study aimed to investigate how exosomal circRNAs are involved in the diagnosis and progression of gastric cancer (GC). Methods: Serum exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis and Western blot. CCK-8, colony formation and transwell assays were conducted to study the function of hsa_circ_0050547 (named as circ50547). qRT-PCR was used to quantify the expression of circ50547 in GC tissues and serum exosomes. Fluorescence in situ hybridization was applied to detect the cellular distribution of circ50547. Stemness and drug-resistance were detected by sphere formation, WB, flow cytometry and half-maximal inhibitory concentration analyses. Bioinformatic analyses, luciferase experiments, qRT-PCR and WB were used to investigate molecular mechanisms. Results: We discovered for the first time a new type of GC-derived exosomal circRNA, circ50547. We found that circ50547 is highly expressed in both GC tissues and serum exosomes. Interestingly, we observed that the diagnostic value of exosomal circ50547 is superior to that of serum circ50547. Circ50547 overexpression enhanced the proliferation, migration, invasion, stemness and drug resistance of GC cells, while knockdown of circ50547 showed the opposite effect. Mechanistically, circ50547 acted as a sponge for miR-217 to regulate the expression of HNF1B, which promoted gastric cancer progression. Conclusion: Exosomal circ50547 may be a promising marker for the diagnosis and prognosis prediction of GC. These findings suggest that it plays an oncogenic role through miR-217/HNF1B signaling pathway in GC.

The globe is an organically linked whole, and in the pandemic era, COVID-19 has brought heavy public safety threats and economic costs to humanity as almost all countries began to pay more attention to taking steps to minimize the risk of harm to society from sudden-onset diseases. It is worth noting that in some low- and middle-income areas, where the environment for epidemic detection is complex, the causative and comorbid factors are numerous, and where public health resources are scarce. It is often more difficult than in other areas to obtain timely and effective detection and control in the event of widespread virus transmission, which, in turn, is a constant threat to local and global public health security. Pandemics are preventable through effective disease surveillance systems, with nonpharmacological interventions (NPIs) as the mainstay of the control system, effectively controlling the spread of epidemics and preventing larger outbreaks. However, current state-of-the-art NPIs are not applicable in low- and middle-income areas and tend to be decentralized and costly. Based on a 3-year case study of SARS-CoV-2 preventive detection in low-income areas in south-central China, we explored a strategic model for enhancing disease detection efficacy in low- and middle-income areas. For the first time, we propose an integrated and comprehensive approach that covers structural, social, and personal strategies to optimize the epidemic surveillance system in low- and middle-income areas. This model can improve the local epidemic detection efficiency, ensure the health care needs of more people, reduce the public health costs in low- and middle-income areas in a coordinated manner, and ensure and strengthen local public health security sustainably.

Both subsoiling tillage (ST) and ridge and furrow rainfall harvesting (RF) are widely implemented and play an important role in boosting wheat productivity. However, information about the effects of ST coupled with RF during the summer fallow season on wheat productivity and environmental issues remains limited. This study aims to explore the effects of ST coupled with RF on water harvesting, wheat productivity–yield traits, water and nutrient use efficiency and quality, and soil nitrate-N residue in dryland winter wheat–summer fallow rotation at the intersection of southern Loess Plateau and western Huang–Huai–Hai Plain in China in 2018–2022. Three tillage practices—deep plowing with straw turnover (PTST), subsoiling with straw mulching (STSM), and STSM coupled with RF (SRFSM)—are conducted during the summer fallow season. The results indicated that tillage practices during the summer fallow season significantly impacted wheat productivity and soil nitrate-N residue. Compared to PTST, STSM significantly enhanced rainfall fallow efficiency and water use efficiency by 7.0% and 14.2%, respectively, as well as N, P, and K uptake efficiency by 16.9%, 16.2%, and 15.3%, and thus increased grain yield by 14.3% and improved most parameters of protein components and processing quality, albeit with an increase in nitrate-N residue in the 0- to 300-cm soil depth by 12.5%. SRFSM, in turn, led to a further increase in water storage at sowing, resulting in an increase of water use efficiency by 6.8%, as well as N, P, and K uptake efficiency and K internal efficiency by 11.8%, 10.4%, 8.8%, and 4.7%, thereby significantly promoting grain yield by 10.2%, and improving the contents of all the protein components and enhancing the processing quality in grain, and simultaneously reducing the nitrate-N residue in the 0- to 300-cm soil layer by 16.1%, compared to STSM. In essence, this study posits that employing subsoiling coupled with ridge–furrow rainfall harvesting (SRFSM) during the summer fallow season is a promising strategy for enhancing wheat yield, efficiency, and quality, and simultaneously reducing soil nitrate-N residue within the dryland summer fallow–winter wheat rotation system.

Abstract Background Ichthyosis is a common keratotic skin disease with high clinical, etiological and genetic heterogeneity. There are four types of non‐syndromic hereditary ichthyoses, among which autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of recessive Mendelian disorders. ARCI present with different phenotypes and ABCA12 pathogenic variants have been shown to cause complex ARCI phenotypes, including harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Methods A sporadic male patient, clinically diagnosed with CIE, was enrolled in this study. Exome sequencing was combined with Sanger sequencing to confirm the diagnosis and identify the pathogenic variants. In silico predictions were made using multiple software programs, and the identified variants were interpreted using the ACMG guidelines. A review of all literature reported ABCA12 variants was performed to explore genotype–phenotype correlations. Results Compound heterozygous ABCA12 variants [c.5381+1G>A and c.5485G>C (p.Asp1829His)] (NM_173076) were identified. The two variants were not detected in the public database. c.5381+1G>A is predicted to affect ABCA12 mRNA splicing and Asp1829 is highly conserved among various species. In silico analysis suggested that these two variants were responsible for the phenotype of the patient. Genotype–phenotype correlation analysis showed that biallelic truncation variants and/or exon/amino acid deletions in ABCA12 are the most common causes of HI. Biallelic missense variants are most common in LI and CIE. Conclusions The compound heterozygous ABCA12 variants caused the CIE phenotype observed in the patient. The spectrum of ABCA12 pathogenic variants were broaden. Genotype–phenotype correlation analysis provided detailed evidence which can be used in future prenatal diagnosis and can inform the need for genetic counselling for patients with ABCA12‐related ARCIs.

Abstract Background Congenital disorders of glycosylation (CDG) are a type of inborn error of metabolism (IEM) resulting from defects in glycan synthesis or failed attachment of glycans to proteins or lipids. One rare type of CDG is caused by homozygous or compound heterozygous loss‐of‐function variants in mannosidase alpha class 2B member 2 (MAN2B2). To date, only two cases of MAN2B2‐CDG have been reported worldwide. Methods Trio whole‐exome sequencing (Trio‐WES) was conducted to screen for candidate variants. N‐glycan profiles were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). MAN2B2 expression was evaluated by western blotting. MX dynamin like GTPase 1 (MX1) function was estimated via Thogoto virus (THOV) minireplicon assay. Results Trio‐WES identified compound heterozygous MAN2B2 (hg19, NM_015274.1) variants (c.384G>T; c.926T>A) in a CDG patient. This patient exhibited metabolic abnormalities, symptoms of digestive tract dysfunction, infection, dehydration, and seizures. Novel immune dysregulation characterized by abnormal lymphocytes and immunoglobulin was observed. The MAN2B2 protein level was not affected, while LC–MS/MS showed obvious disruption of N‐glycans and N‐linked glycoproteins. Conclusion We described a CDG patient with novel phenotypes and disruptive N‐glycan profiling caused by compound heterozygous MAN2B2 variants (c.384G>T; c.926T>A). Our findings broadened both the genetic and clinical spectra of CDG.

Organic fertilizer substitution is an effective measure for increasing both the quantity and quality of wheat grain while reducing chemical fertilizer input. However, the effects of reducing nitrogen (N) fertilizer combined with organic fertilizer substitution on grain yield, grain protein content and protein yield, plant N accumulation and translocation, N use efficiency, soil fertility, N apparent surplus and nitrate-N residue in rain-fed drought-prone areas remains limited. In this study, field experiments were conducted over four consecutive seasons (2019-2023) at two sites with four treatments: zero N application (ZN), farmer N application (FN), reduced 20% N of FN (RN), and organic fertilizer substituting 20% N of RN (OSN). The results showed that compared with the ZN treatment, the FN, RN and OSN treatments increased grain yield and its components, grain protein content and protein yield, aboveground N accumulation at the anthesis and maturity stages, pre-anthesis N translocation, post-anthesis N accumulation, N use efficiency, soil fertility. Compared with RN and FN, OSN increased grain yield by 17.12% and 15.03%, grain protein yield by 3.31% and 17.15%, grain N accumulation by 17.78% and 15.58%, and N harvest index by 2.63% and 4.45% averaged across years and sites, respectively. Moreover, OSN increased the contents of organic matter, total N, available P and available K in both 0-20 and 20-40 cm soil layers, decreased N apparent surplus and nitrate-N residue in 0-100 cm, and pH in both 0-20 and 20-40 cm soil layer. Fundamentally, this study suggests that integrating a 20% reduction N from conventional farmer practices with the utilization of organic fertilizer to replace 20% of the chemical N fertilizer (OSN) represents an effective strategy. This approach shows promise in enhancing wheat grain yield, grain protein yield, and N use efficiency. Additionally, it supports the improvement of soil fertility while simultaneously reducing soil nitrate-N residues and the apparent surplus of N in rain-fed drought-prone regions.

Background: Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative. Objective: This study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN. Methods: This study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website. Results: This study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29–1.46, I2 = 0%, P

Background: Food allergies impose a large psychosocial burden, including mental, emotional, and social aspects, on both patients and their caregivers. Patients, caregivers, and their families often experience anxiety, isolation, and fear around food allergies. Objective: To assess the real-world mental health burden of food allergies, using the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: Self-reported data from patients with food allergies, and their caregivers, were analyzed from the FARE Food Allergy History and Mental Health Concerns surveys. Odds ratios were also calculated as a measure of association between patient food allergy characteristics and the likelihood of having mental health concerns or a formal mental health diagnosis. Results: The FARE Patient Registry included 1680 patients/caregivers. Anxiety (54%) and panic (32%) were the most common emotions that patients reported as a result of eating the food that produced an allergic reaction. About two-thirds of patients reported mental health concerns related to food allergies (62%), including anxiety after an allergic reaction, anxiety about living with food allergies, and concerns about food avoidance. Caregivers also experienced fear for the safety of their children, and often sought mental health care to cope with worry related to caring for patients with food allergies. The likelihood of having food allergy-related mental health concerns was increased for patients experiencing more than 1 reaction per year (OR 1.68–1.90) and was lowered for patients having a formal mental health diagnosis (OR 0.43). Caregivers filling out the FARE survey for pediatric patients (OR 4.03) and experiencing food allergy-related mental health concerns (OR 2.36) were both significant predictors for having a formal mental health diagnosis. Conclusion: Our study highlights a continuing unmet need for mental health screening and support as part of the management of patients with food allergies.

Abstract Background Membranous nephropathy (MN) is a chronic glomerular disease that leads to nephrotic syndrome in adults. The aim of this study was to identify novel biomarkers and immune-related mechanisms in the progression of MN through an integrated bioinformatics approach. Methods The microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between MN and normal samples were identified and analyzed by the Gene Ontology analysis, the Kyoto Encyclopedia of Genes and Genomes analysis and the Gene Set Enrichment Analysis (GSEA) enrichment. Hub The hub genes were screened and identified by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm. The receiver operating characteristic (ROC) curves evaluated the diagnostic value of hub genes. The single-sample GSEA analyzed the infiltration degree of several immune cells and their correlation with the hub genes. Results We identified a total of 574 DEGs. The enrichment analysis showed that metabolic and immune-related functions and pathways were significantly enriched. Four co-expression modules were obtained using WGCNA. The candidate signature genes were intersected with DEGs and then subjected to the LASSO analysis, obtaining a total of 6 hub genes. The ROC curves indicated that the hub genes were associated with a high diagnostic value. The CD4+ T cells, CD8+ T cells and B cells significantly infiltrated in MN samples and correlated with the hub genes. Conclusions We identified six hub genes (ZYX, CD151, N4BP2L2-IT2, TAPBP, FRAS1 and SCARNA9) as novel biomarkers for MN, providing potential targets for the diagnosis and treatment.

Abstract Objective This study aimed to investigate the clinical infection characteristics and analyze the resistance gene carrying status of carbapenem-resistant Providencia rettgeri via whole genome sequencing (WGS). Methods Carbapenem-resistant P. rettgeri were collected from clinical patients between January 2020 and December 2021, and their susceptibility to 19 antimicrobial drugs was determined using the VITEK 2 Compact system and Kirby–Bauer (KB) disk diffusion method. The Illumina platform was used to perform WGS of the P. rettgeri isolates, and the resistance genes carried by the Carbapenem-resistant P. rettgeri strains were detected via ABRicate software. The phylogenetic tree was constructed by thirty-four strains including twenty-eight strains downloaded from NCBI database and the carbapenem-resistant six P. rettgeri strains in this study. Which based on genomic single nucleotide polymorphism (SNP) to understand the affinities of the carbapenem-resistant P. rettgeri strains. Results Six carbapenem-resistant P. rettgeri strains were isolated from five different clinical departments using the blood, urine, sputum, and secretion specimens. These infected patients are middle-aged and elderly people with a history of severe trauma, tumors, hypertension, and various other underlying diseases, and invasive procedures. Antimicrobial sensitivity testing showed that all strains presented resistance to ampicillin-sulbactam, ceftazidime, ciprofloxacin, levofloxacin, and ertapenem, whereas they exhibited full susceptibility to cefepime and amikacin. Most strains demonstrated high resistance to β-lactams, aminoglycosides, and sulfonamides. Thirty-five resistance genes were identified by ABRicate. All carbapenem-resistant P. rettgeri strains carried aminoglycoside, fluoroquinolone, chloramphenicol, rifampicin, sulfonamide, and β-lactam resistance genes, and most importantly, all strains possessed the carbapenem resistance gene bla NDM−1. The six P. rettgeri strains in this study and the 28 carbapenem-resistant P. rettgeri strains from the NCBI database were divided into four evolutionary groups. The WF3643, WF3849, WF3822, and WF3821 strains in this study were in the same evolutionary group (clade A), while the closely related WF3099 and WF3279 strains were in different evolutionary groups (clade B and clade D), respectively. The WF3099 strain was distantly related to the other five strains. Conclusion Carbapenem-resistant P. rettgeri strains were mostly isolated from middle-aged and older patients with a history of surgery or serious underlying diseases, and they were found to cause multisystem infections. All Carbapenem-resistant P. rettgeri strains in this study carried bla NDM−1 and multiple antimicrobial drug resistance genes. Furthermore, the P. rettgeri strains in this study were closely related, suggesting the possibility of nosocomial infections. Therefore, our study highlights the need for research on P. rettgeri to control the spread of these nosocomial infections.

Hybrid wheel–track systems have found extensive applications due to the advantages a combination of wheels and tracks. However, the coupling influence between the wheeled and tracked mechanisms poses a challenge to stable and efficient controller design and implementation. This paper focuses on the lateral dynamic control of a vehicle in scenarios where both tracks and wheels are in contact with the ground. A dynamic model of a vehicle is first established based on the tire brush model and linearized general track model. Based on the dynamic model, a novel adaptive model predictive control (AMPC) method is designed considering the coupling and nonlinearity of the wheels and tracks to simultaneously regulate both mechanisms. Compared with traditional model predictive control approaches, the AMPC controller takes the side-slip angle and slip ratio as constraints to prevent the vehicle from reaching unstable states. Simulations are conducted to validate the effectiveness of the controller, and the results indicate that the controller has the capacity to optimize the objective’s yaw-rate response while maintaining lateral vehicle stability and preventing slip by imposing constraints.

To address the question of which posture trailing-arm vehicles (TAVs) should be adopted while driving, this study introduces an innovative active posture controller (APC) to improve both path-following and handling stability performance. Leveraging a nonlinear tire model that considers corner load variation and wheel camber, alongside the kinematics and double-track model of TAVs, the impact of vehicle body posture on handling performance has been investigated. To fully utilize the four-wheel independent drive and posture adjustable characteristics of the TAV mechanisms, an integrated nonlinear model predictive control (NMPC) combining APC and tire forces distribution is devised. Through simulations conducted using Simulink-Multibody (2023a), the effectiveness of the proposed controller is demonstrated, particularly when compared to the scheme that does not account for the unique posture adjustment mechanisms of TAVs.

Background: Food allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life. Objective: To assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: The FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed. Results: The FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged 1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients. Conclusion: This is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies.

In this study, the effects of grafting chlorogenic acid (CA) on the antioxidant and probiotic activities of curdlan oligosaccharides (CDOS) were investigated. CDOS with degrees of polymerization of 3–6 was first obtained by degradation of curdlan with hydrogen peroxide and then grafted with CA using a free radical-mediated method under an ultrasonication-assisted Fenton system. The thermal stability and antioxidant ability of CDOS were enhanced after grafting with CA. In vitro fermentation, supplementation of CDOS-CA stimulated the proliferation of Prevotella and Faecalibacterium while inhibiting the growth of harmful microbiota. Notably, the concentration of total short-chain fatty acids and the relative abundance of beneficial bacteria markedly increased after fermentation of CDOS-CA, indicating that CA grafting could improve the probiotic activity of CDOS. Overall, the covalent binding of CDOS and CA could enhance the antioxidant and probiotic activities of CDOS, suggesting potential improvements in gastrointestinal and colonic health.

Introduction Recombinant fusion protein linking coagulation factor IX (FIX) with albumin (rIX-FP) has been shown to be an effective, well-tolerated treatment for patients with severe hemophilia B who had previously received factor replacement therapy. This study investigated the safety and efficacy of rIX-FP in previously untreated patients (PUPs).

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

BackgroundThe central nervous system (CNS) is the most common site of extramedullary invasion in acute lymphoblastic leukemia (ALL), and involvement of the CNS is often associated with relapse, refractory disease, and poor prognosis. Chimeric antigen receptor-T (CAR-T) cell therapy, a promising modality in cancer immunotherapy, has demonstrated significant advantages in the treatment of hematological malignancies. However, due to associated adverse reactions such as nervous system toxicity, the safety and efficacy of CAR-T cell therapy in treating CNSL remains controversial, with limited reports available.Case reportHere, we present the case of a patient with confirmed B-ALL who experienced relapse in both bone marrow (BM) and cerebrospinal fluid (CSF) despite multiple cycles of chemotherapy and intrathecal injections. The infusion of autologous CD19 CAR-T cells resulted in complete remission (CR) in both BM and CSF for 40 days. However, the patient later experienced a relapse in the bone marrow. Subsequently, allogeneic CD19 CAR-T cells derived from her brother were infused, leading to another achievement of CR in BM. Significantly, only grade 1 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events were detected during the treatment period and showed improvement with symptomatic management. During subsequent follow-up, the patient achieved a disease-free survival of 5 months and was successfully bridged to hematopoietic stem cell transplantation.ConclusionOur study provides support for the argument that CNS involvement should not be deemed an absolute contraindication to CAR-T cell therapy. With the implementation of suitable management and treatment strategies, CAR-T therapy can proficiently target tumor cells within the CNS. This treatment option may be particularly beneficial for relapsed or refractory patients, as well as those with central nervous system involvement who have shown limited response to conventional therapies. Additionally, CAR-T cell therapy may serve as a valuable bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients.

ABSTRACTDrug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of Peptostreptococcus and Gemella were significantly increased, while the relative abundances of Campylobacter and Aggregatibacter were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., Peptostreptococcus, Gemella, Campylobacter, and Aggregatibacter, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.IMPORTANCEIt was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.

N-glycans in many proteins are of great concern because of their strong association with food allergies. Triticum aestivum (bread wheat), a major food crop, is known as one of the “Big Eight” allergenic groups. However, little research has been done about N-glycans in wheat glycoproteins. In this study, a soluble wheat glycoprotein was purified from wheat and further identified as globulin-1 S allele (GSA). The wheat GSA displayed significant IgE-binding activity. Moreover, one N-glycosylation site and 6 kinds of N-glycans were identified by mass spectrometry, including 3 high mannose types and 3 complex types. Furthermore, the IgE-binding activity of wheat GSA is proved to be reduced by the removal of N-glycan, thermal treatment (temperatures > 80 °C), and strong acidic treatment (pH 3.0). These findings would provide a better understanding of the effects of N-glycosylation, thermal treatment, and acidic treatment on the molecular characteristics of GSA, and further provide new insights into the development of hypoallergenic wheat products.

Abstract Background By analyzing 23 evaluation indicators included in 14 national basic public health service programs in a region of Hohhot City, Inner Mongolia Autonomous Region, China, the performance of basic public health services in the region in 2021 were analyzed to clarify the implementation and conduct of relevant programs. We also use this study as a basis to radiate the work of municipal basic public health services centered on the region and the outstanding problems reflected and to provide theoretical contents and suggestions that can be referred to for the same regions in central and western China as well as worldwide. Methods Using the TOPSIS method as the basis for the data analysis method, the evaluation indexes are ranked in terms of their proximity to the idealized target, and combined with the entropy value method, Technique for order preference by similarity to an ideal solution (TOPSIS) and rank-sum ratio (RSR) were used to rank 14 basic health care providers by grade. A comprehensive evaluation of the performance of basic public health services in a region of Hohhot City, Inner Mongolia Autonomous Region in 2021 was conducted through a joint model of entropy -weighted TOPSIS and RSR, making full use of the characteristics and advantages of the fuzzy joint, and conducting a comprehensive analysis from the perspective of the ratio weight and the method of graded calculation, making the study more distinguishable and measureable. Results In this study, for the regional basic public health services, a total of 23 evaluation indicators of basic public health service projects were included, among which the top three indicators with the weight of the entropy value method indicators were found to include the rate of Chinese medicine health management for the elderly, the rate of health management for the elderly, and the BCG vaccination rate after the analysis of the weight of the indicators; After the entropy-weighted TOPSIS evaluation showed that the Ci values of the regions were found to be between 0.378 and 0.715 through the calculation of the positive and negative ideal values of each indicator; RSR staging method evaluation showed that three community health centers (X2, X10, X12) had excellent evaluations of basic public health services; The number of evaluations as poor and moderate are 2 (X3, X9) and 9 (X1, X4, X5, X6, X7, X8, X11, X13, X14), respectively; Finally, the results of the entropy-weighted TOPSIS method and the fuzzy joint model of RSR staging method are basically consistent with the overall trend of the above two methods, and the reliability and credibility of the research results are high. Conclusion The entropy-weighted TOPSIS and RSR joint model can evaluate the effectiveness of basic public health services in a more comprehensive and holistic way. The results of the RSR staging results and the related weight ratio analysis show that the basic public health service programs in Hohhot, Inner Mongolia Autonomous Region are relatively balanced, but there are some differences; The same genus of elderly Chinese medicine health management rate, health management rate of the elderly, BCG vaccination rate several indicators accounted for a higher weight, its correlation with the key population-related items is high, suggesting that the future key population health service items should be focused on, and future research should be suggested from two key research.

Abstract Background In the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC. Results This study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance. Conclusions The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.

Magnesium alloys, as the lightest structural alloys, provide the possibility of solving environmental problems by improving energy efficiency. Developing and maintaining nanocrystalline matrix is a huge challenge, and the key to achieving ultra-high strength. The nanocrystalline Ti/AZ61 composite prepared by hot pressing was annealed, and its microstructural evolution was characterized via SEM, XRD, and TEM, including the changes in magnesium matrix, Ti dispersions, and nano-scale precipitates. The density and mechanical properties of annealed composites were tested and analyzed. After annealing treatment at 623 K for 80 h, the average grain size of nanocrystalline Ti/AZ61 composites was 102 nm. 97% of Ti dispersions were submicron sized, and Ti3Al precipitates remained nanometer-sized. Ti dispersions and Ti3Al precipitates were uniformly distributed in the magnesium matrix. Compared with hot pressed composites, the crack that originated from the prior particle boundary (PPB) was restrained for annealed composites. The improved density and PPB bonding strength of annealed Ti/AZ61 composites had a positive impact on strength and plasticity. After annealing treatment for 40 h, the density increased from ∼2.041 g/cm3 to 2.066 g/cm3. The hardness, yield strength, and FFS were 146 HV, 493 MPa, and 5.6%, respectively, with corresponding increasing rates of 7%, 12%, and 65%, respectively.

Abstract Background Blood transfusion and previous stroke history are two independent risk factors of venous thromboembolism (VTE) in stroke patients. Whether the potential interaction of transfusion history and previous stroke history is associated with a greater risk of VTE remains unclear. This study aims to explore whether the combination of transfusion history and previous stroke history increases the risk of VTE among Chinese stroke patients. Methods A total of 1525 participants from the prospective Stroke Cohort of Henan Province were enrolled in our study. Multivariate logistic regression models were used to explore the associations among transfusion history, previous stroke history and VTE. The interaction was evaluated on both multiplicative and additive scales. The odds ratio (95% CI), relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (S) of interaction terms were used to examine multiplicative and additive interactions. Finally, we divided our population into two subgroups by National Institutes of Health Stroke Scale (NIHSS) score and re-evaluated the interaction effect in both scales. Results A total of 281 (18.4%) participants of 1525 complicated with VTE. Transfusion and previous stroke history were associated with an increased risk of VTE in our cohort. In the multiplicative scale, the combination of transfusion and previous stroke history was statistically significant on VTE in both unadjusted and adjusted models (P 5 points (P