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Traumatic deep vein thrombosis (TDVT) refers to deep vein thrombosis resulting from trauma or operation. It is common and can bring about multiple complications such as phlegmasia cerulean dolens that requires limb amputation and life-threatening pulmonary thromboembolism. Studies at cellular andmolecular levels reveal that local cells change after trauma and generate corresponding expression products that further change cell function and transmit messages around according to increased, decreased, activated or unactivated gene expressions. Previous studies have shown that TDVT is a complex disease with multiple factors, genes and systems involved in.1,2Matrix metallo-proteinases (MMPs), which result in excessive degradation of the endothelial basement membrane, are one of themain factors that affect thrombosis and thrombus resolution and the mechanisms have become a hotspot in recent years.

Leukocyte antigen related protein (LAR), a member of the PTP family, has become a potential target for exploring therapeutic interventions for various complex diseases, including neurodegenerative diseases. The reuse of FDA-approved drugs offers a promising approach for rapidly identifying potential LAR inhibitors. In this study, we conducted a structure-based virtual screening of FDA-approved drugs from ZINC database and selected candidate compounds based on their binding affinity and interactions with LAR. Our research revealed that the candidate compound ZINC6716957 exhibited excellent binding affinity to the binding pocket of LAR, formed interactions with key residues at the active site, and demonstrated low toxicity. To further understand the binding dynamics and interaction mechanisms, the 100-ns molecular dynamics simulations were performed. Post-dynamics analyses (RMSD, RMSF, SASA, hydrogen bond, binding free energy and free energy landscape) indicated that the compound ZINC6716957 stabilized the structure of LAR and the residues (Tyr1355, Arg1431, Lys1433, Arg1528, Tyr1563 and Thr1567) played a vital role in stabilizing the conformational changes of protein. In conclusion, the identified compound ZINC6716957 possessed robust inhibitory activity on LAR and merited extensive research, potentially unleashing its significant therapeutic potential in the treatment of complex diseases, particularly neurodegenerative disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Type traits (TTs) can contribute to breeding animals with good economic traits such as production, longevity, fertility, and profitability. Dairy buffaloes are the second largest source of milk supply in the world, and their TTs should be taken into consideration in future dairy buffalo breeding programmes. However, the relationship between TTs and milk production traits in buffalo remains largely unknown. The study aimed to establish an early selection method for buffaloes with desirable milk performance by TTs. Using 1 908 records from 678 buffaloes, the relationship between TTs and milk production traits was analysed and the optimal growth curves of TTs related to milk production traits were constructed. We examined the correlations between 45 TTs (33 body structural, 12 udder and teat morphological traits) and three milk production traits (milk yield (MY), milk fat percentage (MF), and milk protein percentage (MP)). The results showed that the highest correlation was found between MY and udder circumference (r = 0.438), teat length (r = -0.380) or heart girth (r = -0.341). The teat distance and teat circumference exhibited a significant negative correlation with MF and MP. Rump length was the only trait that had a significant positive correlation with milk production traits, suggesting that milk performance could be comprehensively improved by including rump length in the selection procedure. Notably, we found that high milk production traits was obtained from the buffaloes with short teats (<6 cm), small heart girth (<200 cm), large udder circumference (>104 cm), long rump (>39 cm), and small distance between teats. Moreover, an early selection method for buffaloes with excellent milk performance was developed based on the non-linear models. Brody model exhibited the best fitting effect for heart girth and rump length, while the Logistic model displayed the best fitting effect for teat length. Our findings provide theoretical basis for the early selection of buffaloes with desirable milk performance., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Two undescribed nitrogen bridged cassane alkaloids (caesanamides A-B) and five undescribed oxygen bridged cassane diterpenoids (caesalpinins JA-JE), together with six known analogs, were isolated and identified from the seeds of Caesalpinia sappan. Their structures, including the absolute configurations, were unequivocally elucidated by the analysis of comprehensive spectroscopic data, ECD calculations, single-crystal X-ray diffraction and the CASE algorithm. Among them, caesanamides A and B represent the first examples of cassane alkaloids bearing unique ring systems of an amide bridge between C-19/C-20 incorporating a 1,3-oxazolidine (6/6/6/5/6/5) or a 7-one-1,3-oxazepine (6/6/6/5/6/7). Caesalpinin JA is an A/B cis-20-norcassane diterpenoid with a rare five-membered oxygen bridge between C-10/C-18. Biological evaluation showed that cassane alkaloids exhibited significant cytotoxicity against HepG2 cells with IC 50 values of 13.48 ± 1.07 μM (caesanamide A), 18.91 ± 0.98 μM (caesanamide B), and 7.82 ± 0.65 μM (caesanine B). Further flow cytometry analysis revealed that caesanine B could cause G0G1 cell cycle arrest and promote apoptosis in a dose- and time-dependent manner in HepG2 cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, the effects of silver (Ag NPs) and sliver sulfide nanoparticles (Ag 2 S NPs) on nitrogen removal and nitrogen functional microbes in constructed wetlands were investigated. The obtained results demonstrated that inhibition extent on nitrogen removal relied on NPs types and high concentrations NPs showed higher negative effects. 0.5 mg/L Ag NPs had no influence on NH 4 + -N removal, amoA and nxrA gene copies, whereas Ag 2 S NPs and Ag + decreased NH 4 + -N removal by reducing abundances of nitrifying genes. The concentrations of NO 3 - -N and TN in all 0.5 mg/L obviously increased compared with control, resulting from decreasing functional genes and denitrifying bacteria. And 0.5 mg/L Ag NPs exhibited largest inhibitory effects, with the highest NO 3 - -N effluent concentrations. 2 mg/L Ag NPs decreased NH 4 + -N removal, but adverse effects gradually vanished with extension of time, whereas both Ag 2 S NPs and Ag + at 2 mg/L influenced NH 4 + -N transformation and decreased the abundance of amoA and nxrA genes and the AOB Nitrosomonas in CWs. Moreover, 2 mg/L of Ag NPs reduced NO 3 - -N removal by decreasing abundance of nirS and key denitrifying bacteria. To sum up, the inhibition mechanisms concluded from current results were possibly in that Ag NPs exhibited nanotoxicity rather than ionic toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Our present and previous phytochemical investigations on Leptopus lolonum have resulted in the isolation of almost 30 phenylpropanoid-conjugated pentacyclic triterpenoids (PCPTs). During the continuous study on PCPTs, this kind of triterpenoid ester is considered as a natural product with low toxicity because of it's widely distribution in natural plants and edible fruits including kiwi fruit, durian, jujube, pawpaw, apple and pear. In the present work, we report the isolation, structural elucidation and cytotoxic evaluation of four new PCPTs (1-4) which obtained from L. lolonum. In addition, the possible biosynthesis pathway for 28-norlupane triterpenoid and potent effect of phenylpropanoid moiety for increasing the cytotxic effect of triterpenoids were also discussed. Among these compounds, compound 1 exhibited the highest cytotoxic effect on HepG2 cells with IC 50 value of 11.87 μM. Further flow cytometry and western blot analysis demonstrated that 1 caused G1 cell cycle arrest by up-regulated the expression of phosphorylated p53 protein in HepG2 cells and induced cell apoptosis via MAPK and Akt pathways. These results emphasized the potential of PCPTs as lead compounds for developing anti-cancer drugs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stroke is one of the most serious problems that seriously affect people's health and brings huge economic burden to society. The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In recent years, nano drug delivery system has developed rapidly and applied to treat ischemic stroke. Here, we report the synthesis and functionalization of monodisperse hollow structured MnO 2 (H-MnO 2 ). The highly monodisperse H-MnO 2 with uniform morphology was obtained by in situ growing MnO 2 on solid silica nanoparticles and subsequently removing the silica core. After successive modification of poly ethylene glycol(PEG), we further verified their protective effect on ischemic stroke in our study., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Most of Euphorbiaceae plants are considered as folk medicinal plants because of their various pharmacological effects. However, there are eight Leptopus genus plants which belong to Euphorbiaceae have never be investigated. Thus, four Leptopus genus plants were collected to study their chemical constituents and pharmacological activities. In the present work, the cytotoxicities of the extracts of four Leptopus genus plants were evaluated before phytochemical experiments. And nine new phenylpropanoid-conjugated pentacyclic triterpenoids, along with twenty-two known compounds were isolated from the whole plants of Leptopus lolonum. The structures of these new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. All triterpenoids were screened for their cytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Among these isolates, the triterpenoid with a phenylpropanoid unit showed increasing cytotoxicity on cancer cells, which suggested the importance of the phenylpropanoid moiety., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Olfaction and gustation play critical roles in the daily activities of insects by mediating important behaviors, such as locating host plants, mates and oviposition sites. These behaviors are mediated by a series of chemosensory receptor proteins, including odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs). Holotrichia parallela is a worldwide pest on many crops and particularly on peanuts in China. In the present study, we produced Illumina-based transcriptomes from male and female antennae and ultimately identified 47 candidate ORs, 15 GRs and 27 IRs. Based on phylogenetic analyses, the relatedness with other species and possible functions of chemosensory genes were predicted and analyzed, such as the putative OR co-receptor (HparOR40), IR co-receptors (HparIR1 and HparIR27), carbon dioxide receptors (HparGR5 and HparGR14) and sugar receptors (HparGR8, HparGR11 and HparGR13). The differences in expression between genes and between sexes were analyzed using FPKM values and visualized in heat maps. Furthermore, the qRT-PCR results of 26 candidate genes were assessed to validate the differential expression analyses between sexes and between olfactory and non-olfactory tissues. Thirteen genes were more highly expressed in female than in male antennae, whereas four genes had higher expression in male than in female antennae. Twelve genes were predominantly expressed in the antennae as olfactory organs compared with expression in non-olfactory tissues. Our study was the first to annotate the chemosensory receptors of H. parallela, and it will provide a strong foundation for future work on physiology and ecology at the molecular level., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We studied two patients from a nonconsanguineous family with life-long abnormal liver function, hepatomegaly and abnormal fatty acid profiles. Abnormal liver function, hypoglycemia and muscle weakness are observed in various genetic diseases, including medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glycogen storage diseases. The proband showed increased free fatty acids, mainly C8 and C10, resembling fatty acid oxidation disorder. However, no mutation was found in ACADM and ACADL gene. Sequencing of theamylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL) gene showed that both patients were compound heterozygotes for c.118C > T (p.Gln40X) and c.753&#95;756 del CAGA (p.Asp251Glufsx29), whereas their parents were each heterozygous for one of these mutations. The AGL protein was undetectable in EBV-B cells from the two patients. Transcriptome analysis demonstrated a significant different pattern of gene expression in both of patients’ cells, including genes involving in the PPAR signaling pathway, fatty acid biosynthesis, lipid synthesis and visceral fat deposition and metabolic syndrome. This unique gene expression pattern is probably due to the absence of AGL, which potentially accounts for the observed clinical phenotypes of hyperlipidemia and hepatocyte steatosis in glycogen storage disease type IIIa.

Background & Aims: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients., Methods: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers without anti-HBs as a control group. Recombinant HBsAg bearing the most frequent N-glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N-glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity., Results: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV., Conclusions: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Novel lipid-polymer composite microspheres (LP-MS) were prepared by combining pH-sensitive polymer Eudragit S100 with solid lipid Compritol 888 ATO for colonic delivery of 10-hydroxycamptothecin (HCPT), and pH-dependent controlled drug release has been achieved. The colon-specific biodistribution and uptake by the mucosal tissue were examined using coumarin-6-marked LP-MS. It is proved that good in vitro-in vivo relationship has been achieved, with more drugs being delivered to colon and a higher drug level was maintained for a long period. Moreover, in vivo bioavailability of LP-MS was evaluated with conventional enteric microspheres (enteric MS) as reference. After administration of LP-MS, systemic absorption of HCPT was greatly reduced, with area under the curve from 0 to 24h (AUC0-24 h , 2.186 ± 0.27) being significantly lower than that of enteric MS group (6.352 ± 0.696). In conclusion, the novel pH-sensitive LP-MS has potential for colon-specific drug delivery., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Impact of hepatitis B virus genetic barrier, defined as the number and type of nucleotide substitutions required to overcome drug/immune selective pressure, on drug-resistance/immune-escape development is unknown., Methods: Genetic barrier was calculated according to Van de Vijver (2006) in 3482 hepatitis B virus-reverse transcriptase/HBV surface antigen sequences from 555 drug-naïve patients and 2927 antiviral-treated patients infected with hepatitis B virus genotypes A-G., Results: Despite high natural variability, genetic barrier for drug-resistance development is identical amongst hepatitis B virus genotypes, but varies according to drug-resistance mutation type. Highest genetic barrier is found for secondary/compensatory mutations (e.g. rtL80I/V-rtL180M-rtV173L), whilst most primary mutations (including rtM204V-rtA181T/V-rtI169T-rtA194T) are associated with low genetic barrier. An exception is rtM204I, which can derive from a transition or a transversion. Genotypes A and G are more prone to develop immune/diagnostic-escape mutations sT114R and sG130N. Vaccine-escape associated sT131N-mutation is a natural polymorphism in both A and G genotypes., Conclusion: Genetic barrier and reverse transcriptase/HBV surface antigen overlapping can synergistically influence hepatitis B virus drug-resistance/immune-escape development. The different immune-escape potential of specific hepatitis B virus genotypes could have important clinical consequences in terms of disease progression, vaccine strategies and correct HBV surface antigen detection., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In this study, an examination of the potential effect of lipids on the first-pass metabolism of anethol trithione (ATT) was investigated. ATT is metabolized rapidly and extensively in liver into 4-hydroxy-anethole trithione (ATX), which was confirmed using the rat intestinal perfusion with the mesenteric cannulation model. Male Sprague-Dawley rats were orally administered of the lipid-based formulations (prepared by medium chain triglycerides (MCT)), the cyclodextrin formulation and the suspension formulation, respectively. For 6.75 mg/kg groups, ATX/ATT area under the plasma concentration-time curve (AUC) ratio decreased by 87% and 76% after administration of the MCT-based formulations and the cyclodextrin formulation, when compared with the suspension formulation (p < 0.05), respectively; for 2.25 mg/kg groups, it decreased by 53% in the MCT group when compared with the cyclodextrin group (p < 0.05). The saturation of pre-system metabolism of ATT was observed after administration of the MCT-based formulations and the cyclodextrin formulation, likely as a result of enhanced absorption and therefore presentation of higher drug concentrations to liver, when compared with the suspension formulation. A trend toward lower systemic metabolite to parent ratios was evident after administration of the lipid formulations, when compared with the cyclodextrin formulation; however, this was not statistically significant. Further studies on the potential for lipids to inhibit hepatic metabolism are therefore warranted., (Copyright © 2011 Wiley-Liss, Inc.)

Autosomal recessive STAT1 deficiency is associated with impaired cellular responses to interferons and susceptibility to intracellular bacterial and viral infections. We report here a new form of partial STAT1 deficiency in 2 siblings presenting mycobacterial and viral diseases. Both carried a homozygous missense mutation replacing a lysine with an asparagine residue at position 201 (K201N) of STAT1. This mutation causes the abnormal splicing out of exon 8 from most STAT1 mRNAs, thereby decreasing (by ~ 70%) STAT1 protein levels. The mutant STAT1 proteins are not intrinsically deleterious, in terms of tyrosine phosphorylation, dephosphorylation, homodimerization into γ-activating factor and heterotrimerization into ISGF-3, binding to specific DNA elements, and activation of the transcription. Interestingly, the activation of γ-activating factor and ISGF3 was impaired only at early time points in the various cells from patient (within 1 hour of stimulation), whereas sustained impairment occurs in other known forms of complete and partial recessive STAT1 deficiency. Consequently, delayed responses were normal; however, the early induction of interferon-stimulated genes was selectively and severely impaired. Thus, the early cellular responses to human interferons are critically dependent on the amount of STAT1 and are essential for the appropriate control of mycobacterial and viral infections.

Background/aims: To investigate dynamic changes of hepatitis B virus (HBV) quasispecies within the reverse transcriptase (RT) region during the early stage of lamivudine treatment and the correlation with antiviral efficacy., Methods: Twenty-five chronic hepatitis B patients received lamivudine treatment for 48 weeks. Fourteen patients responded to lamivudine, while eleven patients were non-responders. HBV DNA was extracted from serum samples at baseline and week 4. The RT region of HBV was amplified, then cloned and sequenced. Quasispecies complexity and diversity within the RT region were analyzed at baseline and week 4, and viral nucleotide substitution rates during the first 4 weeks were calculated., Results: The quasispecies complexity and diversity were not different between responders and non-responders at baseline (p>0.05). However, the quasispecies complexity and diversity of responders were significantly lower than those of non-responders at week 4 (p<0.01). Furthermore, the viral nucleotide substitution rate of responders was significantly higher than that of non-responders (p<0.05)., Conclusions: The dynamic changes of HBV quasispecies within the RT region showed distinct patterns between responders and non-responders during early stage of lamivudine treatment. The dynamic changes of quasispecies complexity and diversity during the first 4 weeks were correlated with lamivudine antiviral efficacy and antiviral resistance.

Monodispersed spherical gold particles synthesized and modified with n-octadecanethiol (C18-Au) were packed into a 100 microm I.D. capillary column and tested in capillary high-performance liquid chromatography (microHPLC). To the best of our knowledge, this represents the first report on the actual use of micron gold particles as stationary phase in a packed column microHPLC. As measured by scanning electron microscopy, the average diameter of these gold microspheres was 3.5 microm and the surface area, average pore diameter, and average pore volume were 49.4m(2)/g, 4.8 nm, and 0.12 cm(3)/g, respectively. The retention behavior of neutral compounds on the n-octadecanethiol-modified gold microspheres was investigated by separating a mixture of small organic compounds using microHPLC. The results from the experiments show that C18-Au behaves basically as a reversed phase. The test of chemical stability of the C18-Au stationary phase under alkaline condition demonstrates that it is stable with the flushing of a mobile phase at pH 12 for at least 140 h. The C18-Au particles are also mechanically strong enough to withstand pressure up to 52 MPa. The preliminary results in this work prove the feasibility of the fabrication of C18-Au micron particles as a novel stationary phase for packed column microHPLC.

Background/aims: Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of heme biosynthesis characterized by a partial decrease in ferrochelatase (FECH) activity leading to excessive accumulation of protoporphyrin. While a majority of EPP patients only exhibit photosensitivity, a small percentage of patients also develop liver complications and need liver transplantation., Methods: In this study, we have sequenced the ferrochelatase gene of a Chinese EPP patient who suffered from EPP-related liver complications., Results: A nonsense mutation in exon 4, 343C>T, introducing a premature stop codon at position arginine 115, was identified in the proband as well as her symptomatic mother and brother, but was absent in her father. All the family members with overt photosensitivity also carried the low-expressed allele IVS3-48c, whose prevalence in the Chinese Han population was determined to be 41.35% and which was also functional in producing an aberrant 63 bp insertion., Conclusion: We describe the first FECH mutation identified in the Chinese Han population and report a high frequency of the hypomorphic IVS3-48c allele in China.

A styrene-maleic anhydride (SMA) alternating copolymer with ultrahigh molecular weight (M(w)>10(6)) synthesized in super critical carbon dioxide (SC CO(2)) medium was used as hydrophilic polymeric additive in the preparation of polyethersulfone (PES) membranes. The PES/SMA blend membranes were prepared by immersion precipitation process. X-ray photoelectronic spectroscopy (XPS) measurements confirmed that the hydrolyzed SMA preferentially segregated to membrane-coagulant interface during membrane formation. For the PES/SMA blend membranes, no big change was observed in the cross-sectional structure and the mechanical properties were well maintained after SMA addition except that a thicker top layer was formed. The surface morphology analysis by atomic force microscopy (AFM) showed that the membrane surface roughness increased with the added SMA amount. The results of water contact angle, water absorbance measurements and static protein adsorption experiments revealed that the surface enrichment of SMA endowed PES/SMA blend membranes with significantly improved surface hydrophilicity and protein-adsorption resistance.

Background: Fibrosis and enlargement of chronic pancreatitis (CP) can cause biliary stenosis, in which fixed circular stenosis is the common type, by compressing the intrapancreatic portion of the common bile duct. Another type of distal bile duct stenosis is compressed relative stenosis, in which the common bile duct walks along the back of the pancreas partially., Methods: Thirty patients with dilation of the proximal common bile duct (diameter > or = 15 mm) caused by CP underwent overall and systemic exploratory operation at our hospital. All of the patients were followed up for 3.5 to 15 years, averaging 8.5 years., Results: The intrapancreatic portion of the common bile duct was found to walk along the back of the pancreas, and its anterior wall was compressed flat by enlarged pancreas, but the posterior wall showed a good flexibility because there was no pancreas covering. Bake's dilators bigger than No.6 (diameter > or = 4 mm) and No.14 urinary catheter could pass through the distal common bile duct after the posterior wall was separated. Roux-en-Y choledochojejunostomy was performed for 4 patients, and T-tube drainage was carried out for the remaining 26 patients. All of the patients were followed up but 2 were lost. Only 2 patients underwent choledochojejunostomy 3 years after T-tube drainage because of repeated acute pancreatitis attack, and others were normal., Conclusions: Compressed relative stenosis of the distal common bile caused by CP is a clinical sign, and its diagnosis mainly depends on surgical findings. Most patients can be treated by separating the posterior wall of the pancreas and T-tube drainage as well, but to patients with recurrent CP, choledochojejunostomy may be a feasible alternative.

An investigation of aliphatic nitro-compounds in Indigofera carlesii resulted in the identification of two blended novel compounds: 2-O-acryl-3,6-di-O-(3-nitropropanoyl)-alpha-d-glucopyranose and 6-O-acryl-2,3-di-O-(3-nitropropanoyl)-alpha-d-glucopyranose. The structures of the new compounds were elucidated on basis of spectral analysis.