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Abstract Purpose There are few studies on early-onset and late-onset nasopharyngeal cancer (EONPC and LONPC, defined as cancers in those aged

Root regeneration is an important factor influencing the healing rate of graft union and the survival of double-root-cutting grafting. To date, little information is available on how to enhance root regeneration of rootstock in grafted watermelon (Citrullus lanatus) seedlings. In this study, the effects of different light treatments on root regeneration were determined. This revealed that addition of far-red light (Fr) could significantly expedite root formation in the rootstock. Moreover, the results of transcriptome analysis revealed that plant hormone pathway and auxin-related genes were greatly induced by Fr, especially for auxin-response proteins (including CmIAA11, CmIAA17, and CmAUX28), Small auxin-up RNA genes (including CmSAUR20 and CmSAUR50) and the auxin efflux transporter (CmPIN3). In addition, the expression of Phytochrome Interacting Factor (PIFs), such as CmPIF1, CmPIF3 and CmPIF7, was remarkably increased by Fr. These genes may act together to activate auxin-related pathways under Fr treatment. Based on the results of HPLC-MS/MS analysis, the concentrations of different auxin-types in adventitious root were significantly influenced by Fr. Furthermore, the better growth of rootstock root displayed superior vasculature transport activity of the graft union with Fr treatment, which was determined by the acid magenta dyeing experiment. Therefore, all the results suggested that Fr could induce AR formation in rootstocks, which may be associated with the auxin accumulation by regulating the transcriptional level of auxin-related and PIF genes. The findings of this study demonstrated a practicable way to shorten the healing period of graftings and improve the quality of grafted watermelon seedlings, which will provide a theoretical basis for the speeding development of industrialized seedlings production.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are new antidiabetic drugs. Their effects on the respiratory system remain unclear. This study aimed to determine the association between DDP-4 inhibitors and acute respiratory failure (ARF) among patients with type 2 diabetes mellitus (T2DM). A meta-analysis was performed by searching the PubMed, Embase, and CENTRAL databases up to July 3rd, 2024, to identify randomized controlled, double-blind, and placebo controlled-cardiovascular outcomes trials (CVOTs) that enrolled participants with T2DM. A total of 6,532 studies were initially retrieved; ultimately, 5 large CVOTs enrolling 47,714 adult T2DM patients were included in the meta-analysis. Overall, there were a nonsignificant increase in the risk of ARF in the DDP-4 inhibitor group compared with the placebo group (RR, 1.72; 95% CI, 0.59 to 4.97; p = 0.319). This is the first meta-analysis to evaluate the association between DDP-4 inhibitors and ARF among T2DM patients. In general, these findings suggest that DPP-4 inhibitors may slightly, but non-significantly, increase the risk of ARF in T2DM patients. As few studies are available and few ARF events occurred, further well-designed large-scale studies need to be performed.

To develop an environmentally sustainable and efficient extraction method for flavonoids from Moringa oleifera Lam. (M. oleifera) leaves, natural deep eutectic solvents (NADES) with ultrasound-assisted extraction was utilized in this study. After optimization of extraction parameters of NADES, including ultrasonic power, ultrasonic time, and liquid–solid ratio, the extraction yield of ultrasound-assisted NADES (UAN) composed of betaine and urea (Bet-Urea) reached 54.69 ± 0.19 mg RE/g DW, which made a 1.7-fold increase compared to traditional ultrasound-assisted traditional solvent (UATS). UPLC-Q Exactive/MS analysis revealed that M. oleifera leaves flavonoids (MOLF) was mainly composed of Quercetin 3-β-D-glucoside, Rutin, Kaempferol-3-O-glucoside, Vitexin and Quercetin. Furthermore, the COSMO-RS model was employed to verify the optimal compatibility of solubility and activity coefficient between Bet-Urea and the five primary flavonoids in MOLF. In vitro antioxidant assays verified that MOLF extracted by UAN exhibited superior antioxidant activity compared to MOLF extracted by UATS. Overall, the devised process not only augmented the extraction yield of MOLF but also effectively preserved the bioactive compounds, thus promoting the utilization of green extraction solvents in the food industry.

BackgroundPediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified.MethodsWe present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison.ResultsAfter a 12-month follow-up, notable advancements were observed in the patient’s language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors.ConclusionThis is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP.

ABSTRACTIdentification and the time since deposition (TsD) estimation of body fluid stains from a crime scene could provide valuable information for solving the cases and are always difficult for forensics. Microbial characteristics were considered as a promising biomarker to address the issues. However, changes in the microbiota may damage the specific characteristics of body fluids. Correspondingly, incorrect body fluid identification may result in inaccurate TsD estimation. The mutual influence is not well understood and limited the codetection. In the current study, saliva, semen, vaginal secretion, and menstrual blood samples were exposed to indoor conditions and collected at eight time points (from fresh to 30 days). High-throughput sequencing based on the 16S rRNA gene was performed to characterize the microbial communities. The results showed that a longer TsD could decrease the discrimination of different body fluid stains. However, the accuracies of identification still reached a quite high value even without knowing the TsD. Correspondingly, the mean absolute error (MAE) of TsD estimation significantly increased without distinguishing the types of body fluids. The predictive TsD of menstrual blood reached a quite low MAE (1.54 ± 0.39 d). In comparison, those of saliva (6.57 ± 1.17 d), semen (6.48 ± 1.33 d), and vaginal secretion (5.35 ± 1.11 d) needed to be further improved. The great effect of individual differences on these stains limited the TsD estimation accuracy. Overall, microbial characteristics allow for codetection of body fluid identification and TsD estimation, and body fluids should be identified before estimating TsD in microbiome-based stain analyses.IMPORTANCEEmerged evidences suggest microbial characteristics could be considered a promising tool for identification and time since deposition (TsD) estimation of body fluid stains. However, the two issues should be studied together due to a potential mutual influence. The current study provides the first evidence to understand the mutual influence and determines an optimal process for codetection of identification and TsD estimation for unknown stains for forensics. In addition, we involved aged stains into our study for identification of body fluid stains, rather than only using fresh stains like previous studies. This increased the predictive accuracy. We have preliminary verified that individual differences in microbiotas limited the predictive accuracy of TsD estimation for saliva, semen, and vaginal secretion. Microbial characteristics could provide an accurate TsD estimation for menstrual blood. Our study benefits the comprehensive understanding of microbiome-based stain analyses as an essential addition to previous studies.

Microbially enhanced coalbed methane (MECBM) production has drawn significant interest worldwide in recent years since the direct combustion of fossil energy sources including oil and coal, would cause global environmental pollution and have detrimental effects on human health. MECBM shows great potential in producing biomethane and thus reducing fossil fuel related pollution. Although much progress has been achieved in understanding the mechanism of how coal is converted into biomethane, studies have shown that the biodegradation efficiency is still low. The present review mainly focuses on discussing recent advances in enhancing the biomethane yield and affecting key factors. Strategies aimed at improving coal solubility or coal bioavailability, stimulating bacterial growth, changing bacterial communities, and altering metabolic pathways or activity of functional genes of microbacteria exert a significantly positive effect on the yield of biomethane production. Coal rank, coal maceral, coal structure, microbial community, culture condition and culture nutrient are key factors that determine the coal degradation efficiency. Expanded investigations on determining key microorganisms that play decisive roles in the conversion of coal to biomethane and what components of coal are consumed by these bacteria will help to clarify the mechanism underlying the MECBM and provide guidance for future in-situ biostimulation of coalbed-methane production from coal seam.

This study examined the impact of sodium propionate concentration (0–40 g/L) on the methanogenic archaea in an inoculum which was cultured in basal nutrient medium, exploring its mechanisms and nonlinear stress intensity. The results indicated that at low concentrations, propionate-maintained homeostasis of the anaerobic digestion (AD) system and enriched Methanosaeta. However, when the concentration exceeded 16 g/L, the stability of the AD system was disrupted. The methanogenic pathway shifted towards a predominantly hydrogenotrophic pathway, resulting in a significant increase in methane yield. Below concentrations of 28 g/L, the AD system gradually enhanced its ability to utilize propionate in an orderly manner. At concentrations of 24–28 g/L, genera (e.g., Advenella and Methanosarcina) were enriched to adapt to the high-VFA environment. This was accompanied by a significant upregulation of genes related to the methylotrophic and hydrogenotrophic pathways, effectively mitigating propionate inhibition and enhancing methanogenesis. Conversely, excess concentrations (>30 g/L) suppressed methanogenesis-related genes and led to methane production arrest despite activating specialized propionate-metabolizing bacteria such as genus Pelotomaculum schinkii. As such, an increase in the stress intensity of propionate promotes a change in the metabolic pathways of methanogens and increases methane production; however, excessive sodium propionate was not conducive to maintaining the steady state of the system.

Aim This study aims to investigate the clinical value of the Duke Anesthesia Resistance Scale (DARS) in predicting postoperative delirium (POD) after hip fracture surgery. Methods A retrospective study was conducted. Clinical data were collected from the patients who had hip fracture and underwent elective total hip arthroplasty in Shaanxi Provincial People’s Hospital, Third Affiliated Hospital of Xi’an Jiaotong University between January 2022 and June 2023. The Consciousness Fuzzy Assessment Scale was used to evaluate the occurrence of POD on postoperative day 3 (POD 3). The enrolled patients were divided into the POD group (n = 26) and the non-POD group (n = 125). Baseline characteristics, surgical data, postoperative information, and laboratory test results were collected. DARS scores were calculated using the minimum alveolar concentration, end-tidal concentration average (ETAC), and bispectral index (BIS). Multivariate logistic regression analysis was conducted to recognize the independent risk factors for POD after hip fracture surgery. Receiver operating characteristic (ROC) curve was plotted to evaluate the value of DARS in POD prediction. Results The average age of POD group was significantly higher, comparing to non-POD group (P < 0.05). DARS scores were statistically lower in the POD group compared to non-POD group (P < 0.05). Multivariate logistic regression analysis found that age and DARS scores were factors impacting post-operative delirium occurrence after hip fracture surgery (P < 0.05). ROC showed that the area under the curve for DARS in predicting POD after hip fracture surgery was 0.929 (95% CI [0.861–0.997]). The optimal cutoff value was 30. The sensitivity was 95.45%, while the specificity was 84.09%. Conclusion DARS score demonstrates good predictive value in hip fracture patients and is feasible in clinical practice, making it suitable for clinical application and promotion.

Abstract Alloy‐type antimony (Sb) is considered as an attractive candidate anode for high‐energy lithium‐ion batteries (LIBs) because of its high theoretical specific capacity and volumetric capacity. However, Sb suffers from enormous volume variation during cycling, which causes electrode cracking and pulverization, and hence the fast capacity decay and poor cyclability, limiting its practical applications as a LIB anode. Herein, we report a facile, scalable, low‐cost, and efficient route to successfully fabricate BiSb/C composites via a two‐step high‐energy mechanical milling (HEMM) process. The as‐prepared BiSb/C composites consist of nanosized BiSb totally embedded in a conductive carbon matrix. As LIB anodes, BiSb/C‐73 (with 30 wt% carbon) electrodes exhibit excellent Li‐storage properties in terms of stable high reversible capacities, long‐cycle life, and high‐rate performance. Reversible capacities of ∼583, ∼466, ∼433, and ∼425 mAh g−1 at a current density of 500 mA g−1 after 100, 300, 500, and 1000 cycles, respectively, were achieved. In addition, a high capacity of ∼380 mAh g−1 can still be retained at a high rate of 5 A g−1. Such outstanding cycling stability and rate capability could be mainly attributed to the synergistic effects between the ability of nanosized BiSb particles to withstand electrode fracture during Li insertion/extraction and the buffering effect of the carbon matrix. The as‐prepared BiSb/C composites are based on commercially available and low‐cost Bi, Sb, and graphite materials. Interestingly, HEMM is a more convenient, efficient, scalable, green, and mass‐production route, making as‐prepared materials attractive for high‐energy LIBs.

Background: In forensic investigations, accurate estimation of the postmortem interval (PMI) is an important task, but also an ongoing challenge. Especially in cases where the cadaver has been specially treated, for example, by boiling, the determination of PMI becomes extremely difficult. Previous studies have shown that the succession of the microbial community after decomposition of the cadaver can be used to infer PMI. However, the feasibility of determining the PMI of boiled cadavers has not yet been demonstrated. Aims and Objectives: The main objective of this study was to test whether we can infer PMI of boiled cadavers based on the succession of microbial communities. Materials and Methods: SD rats were killed by cervical dislocation. Subsequently, the rat cadavers were divided into the case (boiled cadavers) and control (unboiled cadavers) groups. Rectal samples were collected from the rats for 45 days and at nine time points. High-throughput sequencing of the 16S rRNA gene was performed to characterize the microbial community in the rectum. Results: The results showed that the composition and relative abundance of bacterial communities at the phylum level were significantly different between the case and control groups. The alpha diversity of the microbial community showed a decreasing trend with the decomposition process. Principal coordinate analysis showed that the case and control groups had obvious patterns along the succession of microbial communities. The rectal microbial communities showed a significant linear trend in the time course of decomposition. A random forest model was used to infer PMI. The goodness-of-fit (R2) of the model was 68.00% and 84.00%, and the mean absolute errors were 2.05 and 1.48 days within 45 days of decomposition for the case and control groups, respectively. Conclusions: Our results suggest that microbial community succession could be a potential method to infer PMI of boiled cadavers.

The reuse of support material still hamper the practical application of enzyme immobilization technology in wastewater treatment. Here, a novel strategy based on light-triggered reversible β-cyclodextrin (β-CD)-Azobenzene(Azo) host-guest interaction was developed. First, magnetic Fe3O4 nanoparticles were coated with porous β-CD-containing polymers(PCDP), and then the Azo-modified enzyme was immobilized in normal condition. The immobilization would enhance the stability and catalytic performance of enzymes, and the easy separation from reaction medium could be available with external magnetic field. Over broad ranges of temperature and pH, the immobilized enzyme showed higher activity than free enzyme, and the phenol removal efficiency retained about 58.63% even after five cycles. Under UV light, the photoisomerization of Azo would lead to disassemble of β-CD-Azo interaction, resulting in the detachment of the enzyme, and phenol removal efficiency decreased to only 16%. The support materials could be recovered for continue enzyme immobilization, results based on cyclic process of enzyme immobilization and detachment strongly demonstrated the detachment of enzyme and excellent reusability of Fe3O4@PCDP. And this strategy was proved to be a practical method based on batch experiments on the removal of phenol by tyrosinase (Tyr)-based remediation.

Abstract Background Knee osteoarthritis (OA) and depression are both major health issues influencing the quality of elderly life. The aim of the present study was to explore the prevalence of depression and the factors influencing depression in community-dwelling elderly patients with OA of the knee in China. Methods We conducted a cross-sectional descriptive study. The study included 214 participants aged 60 and older diagnosed with OA of the knee. The depression of the elderly was measured by using the Geriatric Depression Scale (GDS). Participants were asked to complete a demographic questionnaire, the GDS, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the society dimension of Arthritis Impact Measurement Scales 2 (AIMS2). In addition, the participants performed a timed up and go test (TUG) and the stair-climb test (SCT). Results The average age of the participants was 69.2 ± 7.63 years old, their body mass index (BMI) was 25.2 ± 3.85, and their disease duration was 5.9 ± 7.72 years. The mean total score of the GDS was 4.43 ± 2.89, and the GDS scores correlated positively with pain (r = 0.45, P

Abstract Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

Sleep problems in middle-aged and older people can threaten their physical and mental health. Family support is regarded as a key factor that affects sleep quality, but the influence mechanism remains underexplored. This study analyzes the mediating effects of fear of crime (FOC) and loneliness in the relationship between family support and sleep quality, and explores whether gender plays a moderating role between family support and FOC. A questionnaire survey was conducted among 1043 Chinese middle-aged and older people aged 45–93 years. Using 10,000 bootstrapped samples, the study shows that middle-aged and older people who receive more family support have better sleep quality, and FOC and loneliness play mediating role in this association. Gender moderates the relationship between family support and FOC. Compared with men, family support for females has a greater impact on their FOC condition, and the mediating effect of family support on sleep quality through FOC is also greater among women. Family support can affect sleep quality through the chain mediating effect of FOC and loneliness for women. This study provides an in-depth understanding of the relationship between family support and sleep quality.

Linfen mining area is one of the main coalbed methane industrial bases in the eastern margin of Ordos Basin, China. However, there are few studies on the hydrogeochemical characteristics of coalbed-produced water in the area. This article collected water samples from 14 coalbed methane drainage wells and analyzed the ionic concentrations, hydrogen and oxygen isotopes, dissolved inorganic carbon isotopes (δ13CDIC) and trace elements. The results showed that the water of Nos. Five and eight coal seams are both Cl-Na type. The total dissolved solids content was high, ranging from 5011.45 mg/L to 23405.39 mg/L. Hydrogen and oxygen isotope data indicated that the coalbed-produced water in the study area is recharged from atmospheric precipitation. In addition, the HCO3− in the produced water of No. Five coal seam and No. Eight coal seam was negatively correlated with δ13CDIC. The value δ13CDIC in the produced water of No. Five coal seam was heavier than that of No. Eight coal seam. These indicate that microbial degradation occurred more strongly in No. Five coal seam than in No. Eight coal seam. The water-rock interaction in the study area was found to be dominated by cation exchange and dissolution filtration through the relationships between anion and cation.

Abstract Highly efficient electrochemical water splitting is of prime importance in hydrogen energy but is suffered from the slow kinetics at the anodic oxygen evolution reaction. Herein, combining the surface activation with the heterostructure construction strategy, the CoP/Fe‐Co9S8 heterostructures as the pre‐catalyst for highly efficient oxygen evolution are successfully synthesized. The catalyst only needs 156 mV to reach 10 mA cm−2 and keeps stable for more than 150 h. Inductively coupled plasma optical emission spectrometry, in situ Raman spectroscopy and density functional theory calculations verify that the introduction of Fe can promote the formation of highly active Co(IV)–O sites and lead to a self‐termination of surface reconstruction, which eventually creates a highly active and stable oxygen evolution catalytic surface. Besides, the catalyst also demonstrates high hydrogen evolution reaction activity with an overpotential of 62 mV@10 mA cm−2. Benefiting from its bifunctionality and self‐supporting property, the membrane electrode assembly electrolyzer equipped with these catalysts achieves high overall water splitting efficiency of 1.68 V@1 A cm−2.

With the development of aquaculture, wastewater treatment and diseases have been paid more and more attention. The question of how to improve the immunity of aquatic species, as well as treat aquaculture wastewater, has become an urgent problem. In this study, duckweed with a high protein content (37.4%) (Lemna turionifera 5511) has been employed as a feedstock for aquatic wastewater treatment and the production of antimicrobial peptides. Penaeidins 3a (Pen3a), from Litopenaeus vannamei, were expressed under the control of CaMV-35S promoter in duckweed. Bacteriostatic testing using the Pen3a duckweed extract showed its antibacterial activity against Escherichia coli and Staphylococcus aureus. Transcriptome analysis of wild type (WT) duckweed and Pen3a duckweed showed different results, and the protein metabolic process was the most up-regulated by differential expression genes (DEGs). In Pen3a transgenic duckweed, the expression of sphingolipid metabolism and phagocytosis process-related genes have been significantly up-regulated. Quantitative proteomics suggested a remarkable difference in protein enrichment in the metabolic pathway. Pen3a duckweed decreased the bacterial number, and effectively inhibited the growth of Nitrospirae. Additionally, Pen3a duckweed displayed better growth in the lake. The study showed the nutritional and antibacterial value of duckweed as an animal feed ingredient.

Most of studies for hydrogen bonds focus on the static model especially between two polar atoms. In contrast, introducing the third polar atom may emerge the competitive hydrogen bonds, which would represent a distinct perspective to perturb the catalytic chemical transformation. Herein, we report quantum mechanics calculations and quasi-classical direct dynamics simulations that demonstrate a triangle form of proton accepters enabled by Cl− anion can afford diverse hydrogen bonds, which control the reactivity and selectivity of Rh catalyzed phenol functionalization. A redox mechanism for carbene insertions with notable ligand effect was discovered and supported by both calculations and the experimental kinetic isotopic effect. The quaternary ammonium additive can stabilize key oxonium ylide intermediates with O–H⋯Cl hydrogen bonds that inhibit the common O–H insertion and promote the carbene C–H insertion product. The nonclassical dynamic hydrogen bonds coupling with Rh complex dissociation may result in an intermediate shuttle of oxonium ylides, which unify the site-selective of the direct phenol functionalization.

Plant regeneration is important for vegetative propagation, detoxification and the obtain of transgenic plant. We found that duckweed regeneration could be enhanced by regenerating callus. However, very little is known about the molecular mechanism and the release of volatile organic compounds (VOCs). To gain a global view of genes differently expression profiles in callus and regenerating callus, genetic transcript regulation has been studied. Auxin related genes have been significantly down-regulated in regenerating callus. Cytokinin signal pathway genes have been up-regulated in regenerating callus. This result suggests the modify of auxin and cytokinin balance determines the regenerating callus. Volatile organic compounds release has been analysised by gas chromatography/ mass spectrum during the stage of plant regeneration, and 11 kinds of unique volatile organic compounds in the regenerating callus were increased. Cyclohexane treatment enhanced duckweed regeneration by initiating root. Moreover, Auxin signal pathway genes were down-regulated in callus treated by cyclohexane. All together, these results indicated that cyclohexane released by regenerating callus promoted duckweed regeneration. Our results provide novel mechanistic insights into how regenerating callus promotes regeneration.

Osteoarthritis (OA) is now becoming the main disease that affects public health. There is no specific medicine used for OA in clinical application until now. Recently, several studies demonstrated that OA is closely related to the complement system, and some complement regulators such as N-terminal non-collagenous domain 4 (NC4) aimed at alleviating OA have shown a promising therapeutic effect. However, targeting ability is the main limitation for NC4. In this study, a fusion protein named heparin-binding domain-N-terminal non-collagenous domain 4 (HB-NC4) was proposed to solve this problem, which could provide a better way for OA treatment. First, HB-NC4 plasmid was constructed using ClonExpress II one-step ligation kit method. And Escherichia coli BL21 was utilized to express the fusion protein, Ni2+-sepharose, and a desalting gravity column were introduced to purify HB-NC4. The results showed that 0.84 mg HB-NC4 could be obtained from a 1 L culture medium with a purity higher than 92.6%. Then, the hemolytic assay was introduced to validate the anti-complement activity of HB-NC4; these results demonstrated that both HB-NC4 and NC4 had a similar anti-complement activity, which indicated that heparin-binding (HB) did not affect the NC4 structure. Targeting ability was investigated in vivo. HB-NC4 showed a higher affinity to cartilage tissue than NC4, which could prolong the retention time in cartilage. Finally, the destabilization of the medial meniscus (DMM) model was applied to investigate HB-NC4 pharmacodynamics in vivo. The results indicated that HB-NC4 significantly slowed cartilage degradation during the OA process. In summary, compared with NC4, HB-NC4 had better-targeting ability which could improve its therapeutic effect and prolonged its action time. It could be used as a new complement regulator for the treatment of OA in the future.

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality via modulating the host response, pharmacokinetic herb–drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5′-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations. Key Words: XueBiJing, Antibiotic, Combination drug therapy, Sepsis, Pharmacokinetic compatibility, Herb‒drug interaction

Growing evidence indicates that the dysregulation of mitochondrial calcium (Ca2+) plays a critical role in the growth of tumor cells, including colorectal cancer (CRC). However, the underling mechanism is not fully elucidated. In this study, the regulatory effects of mitochondrial Ca2+ on phosphodiesterase 2 (PDE2)/cAMP/PKA axis and the phosphorylation of mitochondrial transcription factor A (TFAM) as well as the growth of CRC cells were systematically investigated both in vitro and in vivo. Our findings demonstrated that MCU-induced mitochondrial Ca2+ uptake activated mitochondrial PDE2 in CRC cells. Moreover, overexpression MCU in CRC led to a 1.9-fold increase in Ca2+ uptake compared to control cells. However, knockdown of MCU resulted in 1.5-fould decrease in Ca2+ uptake in mitochondria compared to the controls. Activation of mitochondrial PDE2 significantly inhibited the activity of mitochondrial protein kinase A (PKA), which subsequently leads to decreased phosphorylation of TFAM. Our data further revealed that PKA regulates the phosphorylation of TFAM and promotes the degradation of phosphorylated TFAM. Thus, TFAM protein levels accumulated in mitochondria when the activity of PKA was inhibited. Overall, this study showed that the overexpression of MCU enhanced CRC growth through promoting the accumulation of TFAM proteins in mitochondria. Conversely, knockdown of MCU in CRC cells resulted in decreased CRC growth. Collectively, these data suggest that the mitochondrial Ca2+-activated PDE2/cAMP/PKA axis plays a key role in regulating TFAM stability and the growth of CRC cells.

RNA-binding proteins (RBPs) interacting with target RNAs play essential roles in RNA metabolism at the post-transcription level. Perturbations of RBPs can accelerate cancer development and cause dysregulation of the immune cell function and activity leading to evade immune destruction of cancer cells. However, few studies have systematically analyzed the potential prognostic value and functions of RBPs in squamous cell carcinoma of head and neck (SCCHN). Here, for the first time, we comprehensively identified 92 differentially expressed RBPs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model was constructed with six RBPs, including NCBP2, MKRN3, MRPL47, AZGP1, IGF2BP2, and EZH2, and validated by the TCGA test set, the TCGA all set, and the GEO data set. In addition, the risk score was related to the clinical stage, T classification, and N classification. Furthermore, the high-risk score was significantly correlated with immunosuppression, and low expression of EZH2 and AZGP1 and high expression of IGF2BP2 were the main factors. Thus, the risk model may serve as a prognostic signature and offer highlights for individualized immunotherapy in SCCHN patients.

Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.

Human drivers’ behavior, which is very difficult to model, is a very complicated stochastic system. To characterize a high-accuracy driver behavior model under different roadway geometries, the paper proposes a new algorithm of driver behavior model based on the whale optimization algorithm-restricted Boltzmann machine (WOA-RBM) method. This method establishes an objective optimization function first, which contains the training of RBM deep learning network based on the real driver behavior data. Second, the optimal training parameters of the restricted Boltzmann machine (RBM) can be obtained through the whale optimization algorithm. Finally, the well-trained model can be used to represent the human drivers’ operation effectively. The MATLAB simulation results showed that the driver model can achieve an accuracy of 90%.

Protein is one of the three major macronutrients and is essential for health. The reaction of α-dicarbonyl compounds (α-DCs) with glutenin during heat processing can modify its structure, thereby reducing its digestibility. Furthermore, advanced glycation end products (AGEs) formed by the Maillard reaction are associated with long-term diabetes-related complications. In this study, we established a heat processing reaction system for α-DCs and glutenin by simulating common food processing conditions. An in vitro digestion model was used to study the digestibility of glycated glutenin; whereupon the effects of the digestion products on macrophage inflammatory response were further investigated. It was found that reaction conditions, including temperature, treatment duration, pH, and reactant mass ratio, can significantly affect the digestibility of glycation glutenin, in which the mass ratio of reactants has the most significant influence. We demonstrated that when the mass ratio of glutenin to methylglyoxal (MGO) was 1:3, the level of inflammation induced by glycated glutenin was the highest. The mass ratio of reactants significantly affects the digestibility of glycation glutenin and the level of macrophage-induced inflammatory response. This suggests that it is possible to protect the nutritional value of protein and improve food safety by controlling the heat processing conditions of wheat products.

A low-cost and eco-friendly superabsorbent composite is prepared through the free-radical graft co-polymerization of wheat bran (WB), acrylic acid (AA) and laterite (LA) in an aqueous solution. Elemental map, scanning electron microscopy and Fourier transform infrared spectra revealed that the LA evenly distributed in the superabsorbent composite and wheat bran-g-poly(acrylic acid)/laterite (WB-g-PAA/LA) formed successfully. Thermogravimetric analysis confirmed that the WB-g-PAA/LA had high thermal stability. Furthermore, the properties of the WB-g-PAA/LA, such as swelling in saline solutions and degradation, are also assessed. The final WB-g-PAA/LA (5 wt%) superabsorbent composite attained an optimum water absorbency of 1425 g g−1 in distilled water and 72 g g−1 in 0.9 wt% NaCl solution. The water absorbency of WB-g-PAA/LA (10 wt%) is even greater than that of the WB-g-PAA. Moreover, the water-retention capacity of WB-g-PAA/LA (5 wt%) is high, and the water-retention process followed a zero-order reaction. The reaction rate constant is 8.2428 × 105 exp(−Ea/RT) and the apparent activation energy (Ea) is 35.11 kJ mol−1. Furthermore, WB-g-PAA/LA (5 wt%) may regulate the release of urea, indicating that the superabsorbent composite could provide a promising application as a urea fertilizer carrier. Additionally, it increased the germination and growth rates of Glycyrrhiza uralensis Fisch, suggesting it could influence the growth of Chinese herbal medicine.

Roseobacter denitrificans is a member of the widespread marine Roseobacter genus. We report the first characterization of a truncated hemoglobin from R. denitrificans (Rd. trHb) that was purified in the heme-bound form from heterologous expression of the protein in Escherichia coli. Rd. trHb exhibits predominantly alpha-helical secondary structure and absorbs light at 412, 538 and 572 nm. The phylogenetic classification suggests that Rd. trHb falls into group II trHbs, whereas sequence alignments indicate that it shares certain important heme pocket residues with group I trHbs in addition to those of group II trHbs. The resonance Raman spectra indicate that the isolated Rd. trHb contains a ferric heme that is mostly 6-coordinate low-spin and that the heme of the ferrous form displays a mixture of 5- and 6-coordinate states. Two Fe-His stretching modes were detected, notably one at 248 cm-1, which has been reported in peroxidases and some flavohemoglobins that contain an Fe-His-Asp (or Glu) catalytic triad, but was never reported before in a trHb. We show that Rd. trHb exhibits a significant peroxidase activity with a (kcat/Km) value three orders of magnitude higher than that of bovine Hb and only one order lower than that of horseradish peroxidase. This enzymatic activity is pH-dependent with a pKa value ~6.8. Homology modeling suggests that residues known to be important for interactions with heme-bound ligands in group II trHbs from Mycobacterium tuberculosis and Bacillus subtilis are pointing toward to heme in Rd. trHb. Genomic organization and gene expression profiles imply possible functions for detoxification of reactive oxygen and nitrogen species in vivo. Altogether, Rd. trHb exhibits some distinctive features and appears equipped to help the bacterium to cope with reactive oxygen/nitrogen species and/or to operate redox biochemistry.

Fluorination has been widely used in chemical synthesis, but is rare in nature. The only known biological fluorination scope is represented by the fl pathway from Streptomyces cattleya that produces fluoroacetate (FAc) and 4-fluorothreonine (4-FT). Here we report the identification of a novel pathway for FAc and 4-FT biosynthesis from the actinomycetoma-causing pathogen Nocardia brasiliensis ATCC 700358. The new pathway shares overall conservation with the fl pathway in S. cattleya. Biochemical characterization of the conserved domains revealed a novel fluorinase NobA that can biosynthesize 5’-fluoro-5’-deoxyadenosine (5’-FDA) from inorganic fluoride and S-adenosyl-l-methionine (SAM). The NobA shows similar halide specificity and characteristics to the fluorination enzyme FlA of the fl pathway. Kinetic parameters for fluoride (Km 4153 μM, kcat 0.073 min-1) and SAM (Km 416 μM, kcat 0.139 min-1) have been determined, revealing that NobA is slightly (2.3 fold) slower than FlA. Upon sequence comparison, we finally identified a distinct loop region in the fluorinases that probably accounts for the disparity of fluorination activity.

The fuzzy membership function has non-collapsability and can be used to characterize uncertainties that cannot be explored by sudden events. As the membership function does not satisfy the complementarity law, a single membership function cannot simultaneously characterize the positive and negative aspects of things. This article considers structured fuzzy data with negative uncertainty information, which is modeled using bipolar fuzzy graphs. On this basis, we consider the connectivity remainder of the model and obtain the corresponding theoretical results. In addition, we have discussed some related fractional factor issues. [ABSTRACT FROM AUTHOR]