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Abstract Background Halophiles possess several unique properties and have broad biotechnological applications including industrial biotechnology production. Halomonas spp., especially Halomonas bluephagenesis, have been engineered to produce various biopolyesters such as polyhydroxyalkanoates (PHA), some proteins, small molecular compounds, organic acids, and has the potential to become a chassis cell for the next-generation of industrial biotechnology (NGIB) owing to its simple culture, fast growth, contamination-resistant, low production cost, and high production value. An efficient genome editing system is the key for its engineering and application. However, the efficiency of the established CRISPR-Cas-homologous recombination (HR) gene editing tool for large DNA fragments was still relatively low. In this study, we firstly report a CRISPR-Cas9 gene editing system combined with a non-homologous end joining (NHEJ) repair system for efficient large DNA fragment deletion in Halomonas bluephagenesis. Results Three different NHEJ repair systems were selected and functionally identified in Halomonas bluephagenesis TD01. The NHEJ system from M. tuberculosis H37Rv (Mt-NHEJ) can functionally work in H. bluephagenesis TD01, resulting in base deletion of different lengths for different genes and some random base insertions. Factors affecting knockout efficiencies, such as the number and position of sgRNAs on the DNA double-strands, the Cas9 protein promoter, and the interaction between the HR and the NHEJ repair system, were further investigated. Finally, the optimized CRISPR-Cas9-NHEJ editing system was able to delete DNA fragments up to 50 kb rapidly with high efficiency of 31.3%, when three sgRNAs on the Crick/Watson/Watson DNA double-strands and the arabinose-induced promoter Para for Cas9 were used, along with the background expression of the HR repair system. Conclusions This was the first report of CRISPR-Cas9 gene editing system combined with a non-homologous end joining (NHEJ) repair system for efficient large DNA fragment deletion in Halomonas spp. These results not only suggest that this editing system is a powerful genome engineering tool for constructing chassis cells in Halomonas, but also extend the application of the NHEJ repair system.

Aiming at the problem of high line loss caused by the access station of distributed generation (DG), a two-stage coordinated line loss reduction model based on elephant herding optimization (EHO) and second-order cone programming (SOCP) was put forward by using static var generators (SVG) and energy storage system (ESS) to reduce the line loss from reactive and active power aspects, respectively. Firstly, based on the elephant herding optimization, the location model of distributed generation, SVG and ESS was constructed and determined. On this basis, a cooperative line loss reduction model is proposed, which takes into account multiple line loss reduction methods, such as SVG reactive power compensation device and energy storage. By properly dealing with power flow constraints of distributed generation, the influence of operation control mode of distributed generation on optimal distribution and line loss reduction is precisely explained. The constraint is transformed into a second-order cone programming problem by using second-order cone relaxation. In this way, the coordinated reduction of line loss is realized, and the goal of line loss minimization and voltage stability maximization is achieved. Finally, a practical station is taken as an example to verify the correctness of the proposed model and algorithm and the effectiveness of the proposed method.

Abstract Objective To determine whether white matter hyperintensity (WMH) volumes in specific regions are associated with Parkinson's disease (PD) compared to non‐PD controls, and to assess their impact on motor signs through cross‐sectional and longitudinal analyses. Methods A total of 50 PD participants and 47 age‐ and gender‐matched controls were enrolled. All PD participants were followed up for at least 2 years. To detect regions of greater WMH in the PD, the WMH volume of each region was compared with the corresponding region in the control group. Linear regression and linear mixed effects models were respectively used for cross‐sectional and longitudinal analyses of the impact of increases in WMH volume on motor signs. Results The PD group had greater WMH volume in the occipital region compared with the control group. Cross‐sectional analyses only detected a significant correlation between occipital WMH volume and motor function in PD. Occipital WMH volume positively correlated with the severity of tremor, and gait and posture impairments, in the PD group. During the follow‐up period, the participants' motor signs progressed and the WMH volumes remained stable, no longitudinal association was detected between them. The baseline occipital WMH volume cannot predict the progression of signs after adjustment for baseline disease duration and the presence of vascular risk factors. Interpretation PD participants in this study were characterized by greater WMH at the occipital region, and greater occipital WMH volume had cross‐sectional associations with worse motor signs, while its longitudinal impact on motor signs progression was limited.

Understanding the reproductive characteristics of a species is of crucial for accurate stock assessment and management plans to ensure sustainable fisheries. In this study, the size at 50% sexual maturity (L50) parameters in different bio-ecological provinces were estimated for bigeye tuna, Thunnus obesus, sampled from the Eastern Pacific Ocean tuna fisheries-dependent survey from 2013 to 2019. The overall sex ratio of the catch during the sampling differed significantly from 1:1. Bigeye tuna exhibit sexual dimorphism in the growth of males and females, with a clear shift in predominance from female to male with increasing sizes. In the North Pacific Sub-tropical Gyre (east) (NPST-east), North Pacific Tropical Gyre (NPTG), Pacific North Equatorial Countercurrent (PNEC), and Pacific Equatorial Divergence (PEQD), females (meals) reached sexual maturity round 102 cm (106 cm), 106 cm (100 cm), 125 cm (110 cm), and 113 cm (110 cm), respectively, the estimated L50 of bigeye tuna was 124.08 cm, 121.97 cm, 139.92 cm and 132.45 cm, respectively. The degree of populations mixing between equatorial (PNEC and PEQD) and high-latitude regions (NPST-east and NPTG) is extremely small, but it is reasonably high between the NPST-east and NPTG or PNEC and PEQD. These parameters were significantly different, suggesting the occurrence of a spatial difference in the size-at-maturity of bigeye tuna between these bio-ecological provinces. The findings of this study provide the key information for understanding the life history of bigeye tuna in the Eastern Pacific Ocean and will contribute to the conservation and sustainable yield of this species.

Abstract Background No well‐performing nomogram has been developed specifically to predict individual‐patient cancer‐specific survival (CSS) and overall survival (OS) among patients with resectable colorectal liver metastasis (CRLM) who undergo simultaneous resection of primary and hepatic lesions without neoadjuvant chemotherapy (NAC). We aim to investigate the prognosis of patients with resectable CRLM undergoing simultaneous resection of primary and hepatic lesions without NAC. Methods Data of patients with CRLM in the Surveillance, Epidemiology and End Results Program (cohort, n = 225) were collected as the training set, and data of patients with CRLM treated at the National Cancer Center (cohort, n = 180) were collected as the validation set. The prognostic value of the clinicopathological parameters in the training cohort was assessed using Kaplan‒Meier curves and univariate and multivariate Cox proportional hazards models, and OS and CSS nomograms integrated with the prognostic variables were constructed. Calibration analyses, receiver operating characteristic (ROC) curves, and decision curve analyses (DCAs) were then performed to evaluate the performance of the nomograms. Results There was no collinearity among the collected variables. Three factors were associated with OS and CSS: the pretreatment carcinoembryonic antigen (CEA) concentration, pathologic N (pN) stage, and adjuvant chemotherapy (each p

Temperature affects the growth and development of tobacco. With the frequent occurrence of extreme high and low temperature disasters, temperature stress has become one of the important factors restricting the normal growth and physiological functions of flue-cured tobacco. Low temperature stress and high temperature stress are currently the most common disasters in the seedling and maturity stages of flue-cured tobacco, which have a serious impact on the quality and yield of flue-cured tobacco. This article reviews the effects of temperature stress on physiological mechanisms such as growth and development, photosynthetic function, carbon and nitrogen metabolism, and antioxidant system of flue-cured tobacco. It introduced the research progress of related plant proteins and molecular mechanisms in temperature stress, and systematically summarizes the current stress resistance control measures for field temperature stress, including field management and spraying exogenous substances. At present, most agronomic interventions for temperature stress management may not be complete. It is necessary to understand the genetic, biochemical and physiological processes of different varieties in order to identify and select traits, enhance their high-temperature resistance mechanism, and cultivate high-temperature resistant flue-cured tobacco varieties. Looking forward to future research on temperature stress in flue-cured tobacco, including exploring local germplasm resources, cultivating heat-resistant varieties, utilizing methods such as multi omics or cross omics to deeply explore the response mechanism of temperature stress in flue-cured tobacco, developing predictive research on temperature stress in flue-cured tobacco, and developing targeted management measures for stress resistance cultivation, in order to provide scientific support for the prevention of climate disasters and the enhancement of agricultural disaster reduction efficiency for flue-cured tobacco.

Abstract Background The aim of this study was to evaluate the efficacy and safety of osimertinib for the treatment of leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Methods We conducted a systematic review and meta-analysis to aggregate the clinical outcomes of patients with LM from EGFR-mutant NSCLC treated with osimertinib. A comprehensive literature search for published and unpublished studies was implemented in April 2021 of PubMed, EMBASE, the Cochrane Library, and several international conference databases, in accordance with the PRISMA guidelines. Meta-analysis of proportions was conducted to calculate the pooled rate of overall response rate (ORR), disease control rate (DCR), one-year overall survival (OS), and adverse events (AEs). Results A total of eleven studies (five prospective and six retrospective) including 353 patients were included. The majority of patients (346/353, 98.0%) received osimertinib as ≥ 2nd-line treatment for LM, either at a dosage of 80 mg (161/353, 45.6%) or 160 mg (191/353, 54.1%). The pooled rates of ORR and DCR were 42% (95% CI 24% to 59%) and 93% (95% CI 88% to 97%), respectively. The pooled one-year OS rate was 59% (95% CI 53% to 65%) in 233 patients from five studies. The highest incidence of AEs of all grades was rash (53%), followed by diarrhea (45%), paronychia (35%), decreased appetite (35%), and dry skin (27%), based on data from four studies. Conclusions Our study highlighted and confirmed the meaningful efficacy and a manageable safety profile of osimertinib for the treatment of LM from EGFR-mutant advanced NSCLC.

Abstract Small extracellular vesicles (sEVs) have been identified as a noteworthy paracrine mechanism of intercellular communication in diagnosing and managing neurological disorders. Current research suggests that sEVs play a pivotal role in the pathological progression of pain, emphasizing their critical function in the pathological progression of pain in acute and chronic pain models. By facilitating the transfer of diverse molecules, such as proteins, nucleic acids, and metabolites, sEVs can modulate pain signaling transmission in both the central and peripheral nervous systems. Furthermore, the unique molecules conveyed by sEVs in pain disorders indicate their potential as diagnostic biomarkers. The application of sEVs derived from mesenchymal stem cells (MSCs) in regenerative pain medicine has emerged as a promising strategy for pain management. Moreover, modified sEVs have garnered considerable attention in the investigation of pathological processes and therapeutic interventions. This review presents a comprehensive overview of the current knowledge regarding the involvement of sEVs in pain pathogenesis and treatment. Nevertheless, additional research is imperative to facilitate their clinical implementation. Graphical Abstract Schematic diagram of sEVs in the biogenesis, signal transmission, diagnosis, and treatment of pain disorders. Small extracellular vesicles (sEVs) are secreted by multiple cells, loading with various biomolecules, such as miRNAs, transmembrane proteins, and amino acids. They selectively target other cells and regulating pain signal transmission. The composition of sEVs can serve as valuable biomarkers for pain diagnosis. In particular, mesenchymal stem cell-derived sEVs have shown promise as regenerative medicine for managing multiple pain disorders. Furthermore, by modifying the structure or contents of sEVs, they could potentially be used as a potent analgesic method.

Abstract Background Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. Methods In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher’s exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. Results The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P

In situ bioprinting is promising for developing scaffolds directly on defect models in operating rooms, which provides a new strategy for in situ tissue regeneration. However, due to the limitation of existing in situ biofabrication technologies including printing depth and suitable bioinks, bioprinting scaffolds in deep dermal or extremity injuries remains a grand challenge. Here, we present an in vivo scaffold fabrication approach by minimally invasive bioprinting electroactive hydrogel scaffolds to promote in situ tissue regeneration. The minimally invasive bioprinting system consists of a ferromagnetic soft catheter robot for extrusion, a digital laparoscope for in situ monitoring, and a Veress needle for establishing a pneumoperitoneum. After 3D reconstruction of the defects with computed tomography, electroactive hydrogel scaffolds are printed within partial liver resection of live rats, and in situ tissue regeneration is achieved by promoting the proliferation, migration, and differentiation of cells and maintaining liver function in vivo.

Herein, the microwave transmission method is proposed that demonstrates such advantages as non-invasiveness, excellent penetration performance, and fast detection. As a key component of the microwave method water content measurement instrument, the antenna is required to have a smaller radiation size than the inner diameter of the oil pipe. To address this technical challenge, a small-sized microwave projection method based on water content measurement antenna is designed in this study for the water content measurement of oil-water mixtures in downhole pipelines. Also, the half-cut antenna with a size of 17 × 45 m m 2 is proposed to operate in the frequency band of 2–6 GHz (The measured gain of the antenna varies from 2.48 dBi to 4.98 dBi). Then, the designed half-cut antenna is applied to the established water-content test environment for analysis as to the relationship between water content and the variation in transmission coefficient of the half-cut antenna. According to the test results, the relative water content error is about 0.31% between the simulation and measured results for the transmission coefficient S 21 in the range of 0%–30%, while that is about 0.16% for the transmission coefficient S 21 in the range of 40%–100%. The experimental results can be extended to the measurement of the part with high water content of the oil-water mixture in the pipeline, which provides a practical reference for field tests and basic research.

Cyclophosphamide is commonly used in the treatment of various cancers and autoimmune diseases, while concurrently imposing substantial toxicity on the bladder, frequently manifesting hemorrhagic cystitis. Intravesical interventions, such as hyaluronic acid supplementation, present a therapeutic strategy to reinstate bladder barrier function and alleviate the effects of metabolic toxicants. However, it remains a great challenge to achieve efficient cyclophosphamide-induced hemorrhagic cystitis (CHC) management with accelerated tissue repair owing to the low wet-adhesion, poor hemostasis, and acute inflammatory responses. To address these issues, a hemostatic and anti-inflammatory hydrogel adhesive of chitosan methylacryloyl/silk fibroin methylacryloyl (CHMA/SFMA) is developed for promoting the healing of CHC. The obtained hydrogels show a high adhesive strength of 26.21 N/m with porcine bladder, facilitating the rapid hemostasis within 15 s, and reinstate bladder barrier function. Moreover, this hydrogel adhesive promotes the proliferation and aggregation of SV-HUC-1 and regulates macrophage polarization. Implanting the hydrogels into CHC bladders of a SD rat model, they not only can be completely biodegraded in 14 days, but also effectively control hematuria and inflammation, and accelerate angiogenesis, thereby significantly promote the healing of bladder injury. Overall, CHMA/SFMA hydrogels exhibit rapid hemostasis for treating CHC and accelerate muscle tissue repair via angiogenesis and inflammation amelioration, which may provide a new path for managing severe hemorrhagic cystitis in the clinics.

Abstract The rational design of Z‐scheme heterojunction photosystems based on covalent organic frameworks (COFs) is a promising strategy for harnessing solar energy for hydrogen conversion. Herein, a direct Z‐scheme single‐atom photocatalyst based on COF and metal‐organic ring has been constructed through the supramolecular interactions of coral‐like COF (S‐COF) and photosensitized Pd2L2 type metal‐organic ring (MAC‐FA1). The MAC‐FA1/S‐COF heterojunction exhibits good light absorption, efficient charge separation and transfer, slow electron‐hole recombination, and highly dispersed Pd active sites, enabling an efficient and stable H2 evolution reaction. The optimized 4% MAC‐FA1/S‐COF achieves an H2 evolution rate of 100 mmol g−1 h−1 within 5 h and obtains a total accumulated turn‐over number relative to Pd (TONPd) of 437,685 within 20 h, far superior to S‐COF, MAC‐FA1, M‐5/S‐COF, Pd/S‐COF, and M‐5/Pd/S‐COF, which is one of the highest records among COF‐based photocatalysts for solar‐driven H2 evolution. This is the first work to incorporate photosensitized metal‐organic rings/cages into porous crystalline COFs to form a supramolecular Z‐scheme heterojunction, which has significant potential as a high‐performance photocatalyst for solar‐driven H2 production.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Pseudorabies virus can cause inflammation in the central nervous system and neurological symptoms. To further investigate the protective mechanism of PRV XJ delgE/gI/TK in the central nervous system, an intracranial PRV-infection mice model was developed. The results demonstrated that immunization with PRV XJ delgE/gI/TK successfully prevented death caused by PRV-intracranial infection. Subsequently, the brains were collected for transcriptome and metabolome analysis. GO and KEGG enrichment analysis indicated that the differentially expressed genes were primarily enriched in pathways such as TNF, NOD-like receptor, JAK–STAT, MAPK, IL-17 and apoptosis signaling. Metabolomics analysis revealed that the differential metabolites were mainly associated with pathways such as fatty acid degradation, arachidonic acid metabolism, linoleic acid metabolism and unsaturated fatty acid biosynthesis. The combined analysis of metabolites and differentially expressed genes revealed a strong correlation between the differential metabolites and TNF, PI3K, and MAPK signaling pathways. Anti-inflammatory metabolites have been shown to inhibit the inflammatory response and prevent mouse death caused by PRV infection. Notably, when glutathione was injected intracranially and dihydroartemisinin was injected intraperitoneally, complete protection against PRV-induced death in mice was observed. Moreover, PRV activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrates that PRV XJ delgE/gI/TK can protects intracranially infected mice from death by regulating various metabolites with anti-inflammatory functions post-immunization.

The compaction quality of rockfill materials plays a pivotal role in ensuring the stability and durability of runway structures. However, traditional assessment methods relying on limited random sampling may lack representativeness for the entire construction site and overlook potential areas of insufficient compaction. Addressing this challenge, this paper employs the dynamic deformation modulus (EVD), a rapid and nondestructive testing method, to assess the compaction quality of runway rockfill. Subsequently, this paper propose a 3D Conditional Random Field (CRF) model based on EVD to simulate the uncertain spatial distribution of rockfill compaction quality, allowing for the estimation of the overall construction area's compaction quality with a limited number of sample points. The validity of the model is demonstrated through a case study involving a runway expansion project. Additionally, three critical construction factors--namely, measurement points, compaction passes, and compaction materials--are analyzed throughout the construction process. This analysis provides managers with valuable insights and decision-making tools to promptly evaluate the quality of compaction areas, ensuring the stability and durability of the runway.

Abstract Increasing the application of nitrogen fertilizer is the main approach to increase rice production, but it also brings problems of environmental pollution and increases agricultural production costs. Cultivating high‐yielding and high nitrogen use efficiency (NUE) rice varieties is an important approach to solving this problem. The rice varieties carrying dep1 (dense and erect panicle 1) have both high grain yield and high NUE. However, their plant traits have not been fully explored. In this study, two rice near‐isogenic lines carrying dep1 (NIL‐DEP1 and NIL‐dep1) were grown in paddy fields under 0, 120 and 270 kg N ha−1. We analyzed agronomic traits of panicle type, plant type, leaves and roots, and physiological traits of vascular bundles, photosynthetic rate and carbon and nitrogen transport. The results showed that the NIL‐dep1 exhibited higher grain yield and NUE than NIL‐DEP1, mainly due to the higher spikelet number per panicle, grain filling percentage and dry matter production. Compared with NIL‐DEP1, NIL‐dep1 had improved flag leaf morpho–physiological traits, including erect flag leaves, greater leaf thickness and specific leaf weight, higher root dry weight, root length, root volume and root surface area, and a better canopy structure, as reflected by a lower light interception percent and canopy extinction coefficient, leading to better photosynthetic performance and dry matter production. In addition, NIL‐dep1 exhibited better vascular bundle traits of peduncle and enhanced dry matter, stem carbon and nitrogen translocation during grain filling. In conclusion, NIL‐dep1 had high grain yield and NUE by improved agronomic and physiological traits and increasing carbon and nitrogen translocation during grain filling. These traits mentioned above could be used to select and breed high grain yield with high NUE rice varieties.

ObjectiveThere is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI.MethodsIn this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis.ResultsOnly SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively.ConclusionThis represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.

Background: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. Material and methods: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. Results: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value

Objective: Patients undergoing percutaneous transforaminal endoscopic discectomy (PTED) often complain of unbearable intraoperative pain. This study is to observe clinical effectiveness and safety of intradiscal local anesthetic injection for intraoperative pain relief. Methods: Total 268 patients who underwent PTED were analyzed. Patients were divided into intradiscal saline injection group (group C) and intradiscal local anesthetic injection group (group L). Intradiscal mixture was consisted of saline or local anesthetic + methylene blue, the amount of injected mixture was 3 mL. Demographic data, visual analog scale (VAS) and Quebec Back Pain Disability Scale (QBPDS) scores, mean arterial pressure (MAP) and heart rate (HR), total dosage of fentanyl, satisfaction rate of anesthesia and complications were collected at different timepoints. Results: Compared with group C (3.94 ± 0.57), there was a significant reduction of VAS in group L (2.83 ± 0.28) during fibrous annular operation phase (T2). Group L had a lower total dosage of fentanyl (71 [63, 78] μg) and a higher anesthesia satisfaction rate (95.3%) than group C (82 [70, 132] μg and 73.6%, respectively) (P

Abstract Face regions containing rich semantic information appear frequently in the videos. As the video resolution increase dramatically, the face regions will inevitably attract more attentions. This paper proposes a face perception based coding scheme to improve the visual quality of the face regions in UHD videos. A specially tailored face perception model is first utilized to precisely and quickly locate the face regions. Then, a face perception map is generated based on a hierarchical mapping algorithm. Finally, the face perception map is employed as a guidance to optimize the encoding process, including mode decision, block partition and bit allocation. The proposed method is implemented on HEVC to demonstrate the effectiveness. Experimental results on a set of 4K test sequences show that the proposed method can obviously improve the objective and subjective quality of the face regions, while causing only slight quality decline over the rest of the frame. Additionally, the computation required for mode decision and block partition is reduced, thereby saving encoding time cost.

Abstract Background Coffee is the most widely consumed psychostimulant worldwide. Emerging evidence indicates that coffee consumption habit significantly reduces the risk of developing Parkinson’s disease (PD). However, the effect of coffee consumption on nigrostriatal dopaminergic neurodegeneration is still largely unknown. We therefore aim to investigate the role of coffee consumption in nigrostriatal dopaminergic neurodegeneration using dopamine transporter (DAT) imaging in PD and healthy controls (HC). Methods A total of 138 PD patients and 75 HC with questionnaires about coffee consumption, and DAT scans were recruited from the Parkinson’s Progression Markers Initiative cohort. Demographic, clinical, and striatal DAT characteristics were compared across subgroups of current, former, and never coffee consumers in PD and HC, respectively. Furthermore, partial correlation analyses were performed to determine whether there was a relationship between coffee cups consumed per day and striatal DAT characteristics in each striatal region. In addition, the factors that may have influenced the loss of nigrostriatal dopaminergic neurons were included in multiple linear regression analyses to identify significant contributing factors to DAT availability in each striatal region. Results PD patients had lower DAT availability in each striatal region than HC (p

Abstract The role of Gli-similar 2 (Glis2) in hepatic fibrosis (HF) is controversial. In this study, we focused on the functional and molecular mechanisms involved in the Glis2-mediated activation of hepatic stellate cells (HSCs)—a milestone event leading to HF. The expression levels of Glis2 mRNA and protein were significantly decreased in the liver tissues of patients with severe HF and in mouse fibrotic liver tissues as well as HSCs activated by TGFβ1. Functional studies indicated that upregulated Glis2 significantly inhibited HSC activation and alleviated BDL-induced HF in mice. Downregulation of Glis2 was found to correlate significantly with DNA methylation of the Glis2 promoter mediated by methyltransferase 1 (DNMT1), which restricted the binding of hepatic nuclear factor 1-α (HNF1-α), a liver-specific transcription factor, to Glis2 promoters. In addition, the enrichment of DNMT1 in the Glis2 promoter region was mediated by metastasis-associated lung adenocarcinoma transcriptor-1 (MALAT1) lncRNA, leading to transcriptional silencing of Glis2 and activation of HSCs. In conclusion, our findings reveal that the upregulation of Glis2 can maintain the resting state of HSCs. The decreased expression of Glis2 under pathological conditions may lead to the occurrence and development of HF with the expression silencing of DNA methylation mediated by MALAT1 and DNMT1.

Abstract Increasing evidence suggests that Parkinson’s disease (PD) exhibits disparate spatial and temporal patterns of progression. Here we used a machine-learning technique—Subtype and Stage Inference (SuStaIn) — to uncover PD subtypes with distinct trajectories of clinical and neurodegeneration events. We enrolled 228 PD patients and 119 healthy controls with comprehensive assessments of olfactory, autonomic, cognitive, sleep, and emotional function. The integrity of substantia nigra (SN), locus coeruleus (LC), amygdala, hippocampus, entorhinal cortex, and basal forebrain were assessed using diffusion and neuromelanin-sensitive MRI. SuStaIn model with above clinical and neuroimaging variables as input was conducted to identify PD subtypes. An independent dataset consisting of 153 PD patients and 67 healthy controls was utilized to validate our findings. We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, and degeneration of the SN and LC as early manifestations, and cognitive impairment and limbic degeneration as advanced manifestations, while subtype 2 with hyposmia, cognitive impairment, and limbic degeneration as early manifestations, followed later by RBD and degeneration of the LC in advanced disease. Similar subtypes were shown in the validation dataset. Moreover, we found that subtype 1 had weaker levodopa response, more GBA mutations, and poorer prognosis than subtype 2. These findings provide new insights into the underlying disease biology and might be useful for personalized treatment for patients based on their subtype.

The excessive reactive oxygen species (ROS) is a hallmark associated with the initiation and progression of inflammatory bowel disease (IBD), which execrably form a vicious cycle of ROS and inflammation to continually promote disease progression. Here, the gold nanoparticles-embedded ceria nanoparticles (Au/CeO2) with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced ROS. The Au/CeO2 with core-shell and porous structure exhibits significantly higher enzymatic catalytic activities compared with commercial ceria nanoparticles, likely due to the effective exposure of catalytic sites, higher content of Ce (III) and oxygen vacancy, and accelerated reduction from Ce (IV) to Ce (III). Being coated with negatively-charged hyaluronic acid, the Au/CeO2@HA facilitates accumulation in inflamed colon tissues via oral administration, reduces pro-inflammatory cytokines, and effectively alleviates colon injury in colitis mice. Overall, the Au/CeO2@HA with good biocompatibility is a promising nano-therapeutic for treating IBD.

Abstract Brain metastasis (BM) is an important cause of mortality for cancer patients. Many patients were diagnosed with brain metastases at their first visit who have not received any treatment while a subset of patients did not have distant metastases at the first visit and brain metastases were detected during the course of systemic therapies. The difference in their genomic characterization is unclear. 96 lung adenocarcinoma patients were enrolled in our study. 53 patients (55%) had synchronous metastatic brain tumors. 43 (45%) patients had metachronous brain metastases. We performed 168 panel-targeted gene sequencing cerebrospinal fluid (CSF) and plasma samples from patients to identify genomic features of synchronous brain metastases (SBM) and metachronous brain metastases (MBM). In conclusion, CSF liquid biopsies have a priority in detecting gene alteration. A comprehensive comparison of molecular profiling between SBM and MBM revealed the most frequently altered genes in both groups were EGFR and TP53, but with different exon point mutations. RTK-RAS and TP53 pathways were the most affected pathways.

Abstract Mixed-space cluster expansion (MSCE), a first-principles method to simultaneously model the configuration-dependent short-ranged chemical and long-ranged strain interactions in alloy thermodynamics, has been successfully applied to binary FCC and BCC alloys. However, the previously reported MSCE method is limited to binary alloys with cubic crystal symmetry on a single sublattice. In the current work, MSCE is generalized to systems with multiple sublattices by formulating compatible reciprocal space interactions and combined with a crystal-symmetry-agnostic algorithm for the calculation of constituent strain energy. This generalized approach is then demonstrated in a hypothetical HCP system and Mg-Zn alloys. The current MSCE can significantly improve the accuracy of the energy parameterization and account for all the fully relaxed structures regardless of lattice distortion. The generalized MSCE method makes it possible to simultaneously analyze the short- and long-ranged configuration-dependent interactions in crystalline materials with arbitrary lattices with the accuracy of typical first-principles methods.

Plant microbiota composition changes with the environment and host state, suggesting potential for engineering. However, engineering plant microbiomes is promising but currently undeveloped. This study investigated the role of root-associated bacterial microbiomes in poly-γ-glutamic acid (γ-PGA)-induced plant disease resistance. γ-PGA treatment significantly reduced wilt disease caused by Fusarium oxysporum f. sp. chrysanthemi (Foc). Quantitative PCR analysis revealed a 73.2% reduction in Foc abundance in the roots following γ-PGA exposure. However, the disease suppression effect of γ-PGA was notably weakened in sterilized soils or soils treated with bactericide, indicating the essential role of root-associated microbiomes in this process. 16S rRNA gene amplicon sequencing showed that γ-PGA treatments increased the abundance of Proteobacteria, particularly the family Burkholderiaceae, in the roots. Metabolite analysis further indicated that γ-PGA treatment significantly elevated salicylic acid (SA) levels, suggesting that SA played a critical role in the assembly of the root microbiome under γ-PGA treatment. Further experiments confirmed the antagonistic activity and induced systemic resistance (ISR) of Burkholderia sp. against Fusarium wilt. Burkholderia sp. CM72 was found to enhance plant disease resistance through antibiosis and activation of jasmonic acid (JA)-related pathways. In summary, γ-PGA significantly improved plant disease resistance by modulating the SA pathway and promoted the colonization of beneficial microbiota, particularly with Burkholderia sp.

This article explores the mechanism for constructing and the path for implementing an industrial brain in the development of smart cities, with a focus on the case of the Yiwu knitting industry platform in China. Accordingly, our study involved a literature review, questionnaire survey, data analysis, qualitative comparative analysis (QCA), and discussion. Our key finding was that the manufacturing brain evolves in three distinct stages: platform creation, growth, and expansion. The mechanisms of implementing these are functional development, trust creation, and value co-creation, respectively. Specifically, functional development marks the commencement of the industrial brain’s construction, which involves enterprise demand analysis, capability bottleneck identification, data value formation, and platform architecture simplification. Trust building serves as the central mechanism of evolving the manufacturing brain, comprising institutional, relational, and computational trust. Lastly, value co-creation proceeds, which is pivotal for a business paradigm revolution, encompassing connection, linkage, and integration. The main theoretical contribution of this article is to propose a normative analytical framework for revealing the mechanism of construction and the path of implementation of industrial platforms in smart city development. Meanwhile, in its practical contribution, this article provides policy guidance, as developed through our analysis of how an industrial platform can promote the transformation and upgrading of the urban manufacturing industry, to realize smart city construction and the economy and society’s coordinated development.

Auxins play crucial regulatory roles in plants coping with cadmium (Cd) stress. However, the regulatory mechanism by which auxins alleviate Cd toxicity in tomato seedlings remains unclear. Here, we demonstrate that exposure to Cd stress leads to dynamic changes in the auxin response in tomato roots, characterized by an initial increase followed by a subsequent weakening. Under Cd stress, tomato seedlings show primary root- and hypocotyl-growth inhibition, accompanied by the accumulation of Cd and reactive oxygen species (ROS) in the roots. The exogenous application of 1-naphthylacetic acid (NAA) does not mitigate the inhibitory effect of Cd toxicity on primary root growth, but it does significantly enhance lateral root development under Cd stress. Auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA) and 2,3,5-triiodobenoic acid (TIBA), aggravate the growth inhibition of primary roots caused by Cd stress. Additionally, lateral root development was inhibited by NPA. However, applying auxin synthesis inhibitors L-kynurenine (kyn) and yucasin alleviated the tomato root growth inhibition caused by Cd stress; between them, the effect of yucasin was more pronounced. Yucasin mitigates Cd toxicity in tomato seedlings by reducing Cd2+ absorption and auxin accumulation, strengthening ROS scavenging, and reducing cell death in roots. These observations suggest that yucasin potentially mitigates Cd toxicity and improves the tolerance of tomato seedlings to Cd stress.

BackgroundLife's Essential 8 (LE8) is the American Heart Association (AHA)'s recently updated assessment of cardiovascular health (CVH). Metabolic syndrome (MetS) is one of the most common chronic noncommunicable diseases associated with CVH impairment and an increased risk of mortality. However, the association of LE8 with all-cause and disease-specific mortality in the MetS population remains unknown. We aimed to explore these associations in a national prospective cohort study from NHANES 2005-2018.MethodsThe LE8 was calculated according to the assessment criteria proposed by the AHA, which includes health behavior and health factor domains. LE8 scores were categorized as low CVH (0-49), moderate CVH (50-79), and high CVH (80-100). MetS was assessed according to NCEP-ATP III criteria, and mortality data were obtained through prospective linkage to the National Death Index database.Results7839 participants with MetS were included and only 3.5% were in high CVH. In the fully adjusted models, LE8 was negatively associated with both all-cause and cardiovascular disease (CVD) mortality (hazard ratios [HR] and 95% confidence intervals [CI] of 0.978 (0.971,0.984) and 0.972 (0.961,0.984), respectively, both p < 0.0001). Both moderate/high CVH were associated with significantly lower mortality compared to low CVH (both p for trend ConclusionsLE8 scores were negatively associated with all-cause and CVD mortality in the MetS population, while health behaviors had a dominant role. Adherence to higher CVH contributes to the prevention of excessive all-cause and CVD mortality in the MetS population.