Volenrelaxin (LY3540378) increases Renal Plasma Flow: A Randomized Phase 1 Trial.

BACKGROUND AND HYPOTHESIS: Volenrelaxin, is a half-life-extended recombinant human relaxin protein developed for improving kidney perfusion and cardiorenal function. This study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of volenrelaxin following single- and multiple-ascending doses (SAD and MAD) administration. METHODS: In this Phase 1, 4-part, randomized, double-blinded, placebo-controlled SAD and MAD study in healthy participants, SAD participants (n = 56) received an intravenous (IV) or subcutaneous (SC) dose of volenrelaxin or placebo in a dose-ascending manner. MAD participants (n = 77) received volenrelaxin or placebo SC once weekly for 5 weeks. Effective renal plasma flow (ERPF) and measured glomerular filtration rate (mGFR) were determined by para-aminohippurate and iohexol clearance, respectively. RESULTS: Volenrelaxin demonstrated an extended half-life and increased acute and chronic placebo-adjusted ERPF change from baseline by 50% and 44%, respectively (p < 0.0001). Measured GFR was unchanged, while filtration fraction and afferent/efferent renal arteriolar resistances were reduced. Systolic and diastolic blood pressures decreased, and pulse rate increased with increasing volenrelaxin exposures, demonstrating maximal model-derived placebo-adjusted changes (90% confidence interval) of -6.16 (-8.04, -4.28) mmHg, -6.10 (-7.61, -4.58) mmHg, and + 4.39 (3.38, 5.39) bpm, respectively. Adverse events were mild, with no difference in orthostatic hypotension between volenrelaxin and placebo. CONCLUSION: Volenrelaxin was well-tolerated, safe and suitable for weekly SC dosing. Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney disease and chronic heart failure. Clinical trial registration: NCT04768855.

The Influence of Emodin Succinyl Ethyl Ester on Non-alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/d. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

Liquid chromatography-mass spectrometry-based strategy for systematic profiling of chemical components and associated quantitative analysis of quality markers in Qi-Wei-Tong-Bi oral liquid.

Qi-Wei-Tong-Bi oral liquid (QWTB), a famous Chinese medicine preparation composed of seven crude drugs has a good therapeutic effect on rheumatoid arthritis and is widely used in China. However, its chemical composition and quality control have not been comprehensively and systematically investigated. In this study, high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed for its chemical profiling. As a result, 100 components were chemically characterized. Additionally, high-performance liquid chromatography coupled with a quadrupole linear ion trap mass spectrometry method was developed to simultaneously quantify nine bioactive components (hyperoside, ononin, quercetin, sinomenine, magnoflorine, gallic acid, protocatechuic acid, monotropein, and cyclo-(Pro-Tyr)) in multiple-reaction monitoring mode. After successful validation in terms of linearity, precision, repeatability, and recovery, the assay method was applied for the determination of 10 batches of QWTB. The results showed that QWTB was enriched in sinomenine and magnoflorine with the highest amount up to hundreds or even thousands of µg/mL, while quercetin, ononin, cyclo-(Pro-Tyr), and hyperoside were much lower with the lowest content below 10 µg/mL. This study work would help to reveal the chemical profiling and provide a valuable and reliable approach for quality evaluation and even pharmacodynamic material basis studies of QWTB.

[Optimization of processing technology of bark of Ilicis Rotundae Cortex based on quality by design concept].

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests. The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method, and the comprehensive score was calculated. With the comprehensive score as the response value, Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs, and the design space for the processing of Ilicis Rotundae Cortex was built and verified. The results of ANOVA showed that the mathematical model had the P value below 0.05, the lack of fit greater than 0.05, adjusted R~2=0.910 5, and predicted R~2=0.831 0, which indicated that the proposed model had statistical significance and good prediction performance. Considering the factors in production, the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h, moistening for 4 h, and drying at 60-70 ℃ in a blast drier for 2 h. The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible, which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.

[Transdermal diffusion research on functional substances of Jingu Zhitong Gel].

This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG). The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat) sampling system. High performance liquid chromatography(HPLC) content determination method was established to determine the contents of ferulic acid, senkyunolide I, cinnamic acid, hydroxy-ε-xanthoxylin, hydroxy-α-xanthoxylin, and hydroxy-ß-xanthoxylin in the transdermal diffusion solution of JGZTG. The transdermal diffusion law of the components within 16 h was investigated. The results showed that the optimal transdermal diffusion method of JGZTG was as follows: Rat skin was used as the transdermal barrier; normal saline was used as the receiving medium; the dosage of JGZTG was 0.3 g, and the receiving solution was extracted by ethyl acetate. The results of transdermal diffusion showed that the release of ferulic acid, cinnamic acid, and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h. The drug release was a synergic process of diffusion and dissolution, in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations, and liguolactone I followed Higuchi equation. The transdermal diffusion curves of hydroxy-ε-zanthoxylin, hydroxy-α-zanthoxylin, and hydroxy-ß-zanthoxylin showed continuous release within 16 h, and the drug release was skeleton dissolution. The diffusion law followed zero-order equation, first-order equation, and Ritger-Peppas equation. In clonclusion, it is a controlled release of ferulic acid, ligustrone I, cinnamic acid, hydroxy-ε-pyrroxylin, hydroxy-α-pyrroxylin, and hydroxy-ß-pyrroxylin in JGZTG, which can maintain stable blood drug concentration with 16 h, and the cumulative transmittance of each component with 12 h can reach 80% of cumulative transmittance with 24 h, which is in line with the clinical drug use law of bis in die.

[Effects of epimedium total flavone capsules on post-stroke cognitive impairment in rats].

To investigate the effect of epimedium total flavone capsules on post-stroke cognitive impairment(PSCI) in rats. The transient middle cerebral artery occlusion(tMCAO) model was constructed on selected rats, and rats with impaired neurological function were randomly divided into the model group, low, middle, and high dose groups of epimedium total flavone capsules, and nimodipine tablet group. The cognitive function of rats was measured after administration. Pathological changes in brain tissue were observed after hematoxylin-eosin staining(HE). Neuronal nuclei(NeuN) and glial fibrillary acidic protein(GFAP) distribution in brain tissue were tested by immunofluorescent staining. The level of amyloid beta 1-42(Aß_(1-42)), neuron specific enolase(NSE), acetylcholine(ACH), dopamine(DA), 5-hydroxytryptamine(5-HT), norepinephrine(NE), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and hypersensitive C-reactive protein(hs-CRP) in rat serum was tested. Moreover, Western blot was utilized to test the expression of nuclear factor-kappaB(NF-κB), p-NF-κB, alpha inhibitor of NF-κB(IκBα) protein, and p-IκBα protein in the hippocampus. The experimental results showed that epimedium total flavone capsules can improve the cognitive function of model rats, and the mechanism may be related to the regulation of the expression of p-IκBα and p-NF-κB proteins, so as to inhibit inflammatory response induced by ischemia-reperfusion.

Oncolytic Newcastle disease virus expressing the co-stimulator OX40L as immunopotentiator for colorectal cancer therapy.

NDV as an attractive candidate for oncolytic immunotherapy selectively lyses tumor cells but shows limited anti-tumor immunity. Immune co-stimulator OX40 ligand (OX40L) boosts anti-tumor immunity response by delivering a potent costimulatory signal to CD4+ and CD8+ T cells. To improve the anti-tumor immunity of NDV, the recombinant NDV expressing the murine OX40L (rNDV-mOX40L) was engineered. The viral growth kinetics was examined in CT26 cell lines. The ability of rNDV-mOX40L to express mOX40L was detected in the infected tumor cells and tumor tissues. The anti-tumor activity of rNDV-mOX40L was studied in the CT26 animal model. Tumor-specific CD4+, CD8+ and OX40+ T cells were examined by immunohistochemistry staining. The virus growth curve showed that the insertion of the mOX40L gene did not affect the growth kinetics of NDV. rNDV-mOX40L expresses mOX40L and effectively inhibits the growth of CT26 colorectal cancer in vivo. The tumor inhibition rate of the rNDV-mOX40L-treated group was increased by 15.8% compared to that of  NDV-treated group in the CT26 model. Furthermore, immunohistochemistry staining of tumor tissues removed from the CT26 model revealed that intense infiltration of tumor-specific CD4+, CD8+ T cells, especially OX40+ T cells were found in the rNDV-mOX40L-treated group. FACS showed that rNDV-mOX40L significantly enhanced the number of CD4+ and CD8+ T cells in spleen. Moreover, compared to the NDV-treated group, the level of mouse IFN-γ protein in the tumor site increased significantly in the rNDV-mOX40L-treated group. Taken together, rNDV-mOX40L exhibited superior anti-tumor immunity by stimulating tumor-specific T cells and may be a promising agent for cancer immunotherapy.

Competitive electrochemical sensing for cancer cell evaluation based on thionine-interlinked signal probes.

The development of effective methods for tracking cancer cells is of significant importance in the early diagnosis and treatment of tumor diseases. Compared with the developed techniques, the electrochemical assay has shown considerable potential for monitoring glycan expression on the cell surface using nondestructive means. However, the application expansion of the electrochemical strategy is strongly impeded owing to its dependence on electroactive species. In this study, a competitive electrochemical strategy was reported for monitoring cancer cells based on mannose (a typical glycan) as a clinical biomarker. Herein, functionalized carbon nanotubes were used to load the thiomannosyl dimer, and thionine-interlinking signal probes were designed for competitive recognition. After effective competition between cancer cells and the anchored mannose, a decreased current was obtained as the cell concentration increased. Under optimal conditions, the proposed biosensor exhibited attractive performance for cancer cell analysis with a detection limit as low as 20 cells per mL for QGY-7701 and 35 cells per mL for QGY-7703, facilitating great promise for the sensitive detection of cancer cells and thus showing potential applications in cancer diagnosis.

Attenuated African swine fever virus through serial passaging of viruses in cell culture: a brief review on the knowledge gathered during 60 years of research.

African swine fever virus (ASFV) is a highly pathogenic double-stranded DNA virus. It affects various breeds of pigs, causing serious economic losses and health threats because of its rapid spread and high pathogenicity and infectivity. This situation is not helped by the lack of a validated vaccine or effective therapies. Since the 1960s, different strains of ASFV have been subjected to serial passage in a variety of cell lines. The attenuated ASFV strains obtained through serial passage are not only candidates for ASF vaccine research, but also are useful to study the molecular genetic characteristics and pathogenic mechanism of the virus. This review summarizes related studies on the attenuated strains of ASFV acquired through cell passage over the last 60 years, with the aim of providing inspiration for the rational design of vaccines in future.

Genome sequence of the progenitor of the wheat D genome Aegilops tauschii.

Aegilops tauschii is the diploid progenitor of the D genome of hexaploid wheat (Triticum aestivum, genomes AABBDD) and an important genetic resource for wheat. The large size and highly repetitive nature of the Ae. tauschii genome has until now precluded the development of a reference-quality genome sequence. Here we use an array of advanced technologies, including ordered-clone genome sequencing, whole-genome shotgun sequencing, and BioNano optical genome mapping, to generate a reference-quality genome sequence for Ae. tauschii ssp. strangulata accession AL8/78, which is closely related to the wheat D genome. We show that compared to other sequenced plant genomes, including a much larger conifer genome, the Ae. tauschii genome contains unprecedented amounts of very similar repeated sequences. Our genome comparisons reveal that the Ae. tauschii genome has a greater number of dispersed duplicated genes than other sequenced genomes and its chromosomes have been structurally evolving an order of magnitude faster than those of other grass genomes. The decay of colinearity with other grass genomes correlates with recombination rates along chromosomes. We propose that the vast amounts of very similar repeated sequences cause frequent errors in recombination and lead to gene duplications and structural chromosome changes that drive fast genome evolution.

The tissue distribution of Jinzhen oral liquid in healthy and influenza mice.

Jinzhen oral liquid (JZOL) is widely used in China. However, its tissue distribution, a vital part of the efficacy substances research, has not been reported yet. This study characterized its chemical components and its prototypes and metabolites in mice, and investigated its tissue distribution in pathological and healthy mice. Several constituents were characterized, including 55 constituents in JZOL, 11 absorbed prototypes and six metabolites in plasma and tissues. The metabolic pathways were demethylation, dehydration and acetylation. A sensitive, accurate and stable quantitative method was established and applied to the tissue distribution. After administration of JZOL, these seven components were rapidly distributed to various tissues, mainly staying in the small intestine, and less distributed to lung, liver and kidney. Compared with healthy mice, the absorption of baicalin, wogonoside, rhein, glycyrrhizic acid and liquiritin apioside was reduced in influenza mice, but their elimination was slow. However, influenza infection had no obvious effect on the overall distribution of the most important components (baicalin, glycyrrhizic acid and wogonoside) in the plasma or small intestine, but obviously affected the distribution of baicalin in liver. In summary, seven components are rapidly distributed to various tissues, and influenza infection has certain influence on the tissue distribution of JZOL.

[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(â £): classification of hygroscopicity behaviors of capsules].

Hard capsules of traditional Chinese medicine(TCM) have different degrees of hygroscopicity, which affects the stability and efficacy of drugs. In this paper, 30 kinds of commercially available TCM capsules were used as the research object. The hygroscopicity curves of capsule contents, capsule shells, and capsules were tested respectively, and the first-order kinetic equation was used for fitting. The results show that during the 24 h hygroscopicity process, the capsule shell can reduce the weight gain caused by the hygroscopicity of the contents by 0.80%-53.0% and the hygroscopicity rate of the capsule contents by 1.74%-91.3%, indicating that the capsule shell has a strong delay effect on the hygroscopicity of the contents of the TCM capsules. Seven physical parameters of the contents of 30 kinds of TCM capsules were determined, and 14 prescription process-related parameters were sorted out. A partial least squares model for predicting the hygroscopicity rate of the contents of TCM capsules(with shell) for 24 h was established. It is found that the hygroscopicity rate of the capsule shell is positively correlated with the hygroscopicity of the contents of TCM capsules(with shell), suggesting that the capsule shell with a low hygroscopicity rate is helpful for moisture prevention. In addition, the pre-treatment process route of the preparation and the type of molding raw materials affect the hygroscopicity. A larger proportion of the extract in the capsule content and a smaller proportion of the fine powder of the decoction pieces indicate stronger hygroscopicity of the capsule content. The 24 h hygroscopicity rate of 15% was used as the classification node of hygroscopicity strength, and the hygroscopicity rate constant of 0.58 was used as the classification node of hygroscopicity speed. The classification system of hygroscopicity behaviors of TCM capsules was established: the varieties with strong and fast hygroscopicity accounted for about 6.67%, while those with strong and slow hygroscopicity accounted for about 33.3%; the varieties with weak and fast hygroscopicity accounted for about 26.7%, while those with weak and slow hygroscopicity accounted for about 33.3%. The classification system is helpful to quantify and compare the hygroscopicity behavior of different TCM capsules and provides a reference for the quality improvement, moisture prevention technologies, and material research of TCM capsules.

[Discrete element simulation study of mixing process of Guizhi Fuling Capsules: parameter calibration].

The mixing process is a critical link in the formation of oral solid preparations of traditional Chinese medicine. This paper took the extract powder of Guizhi Fuling Capsules and Paeonol powder as research objects. The angle of repose, loose packing density, and particle size of the two powders were measured to calibrate discrete element simulation parameters for the mixing process. The discrete element method was used to calibrate the simulated solid density of Paeonol powder and extract powder of Guizhi Fuling Capsules based on the Hertz-Mindlin with JKR V2 contact model and particle scaling. The Plackett-Burman experimental design was used to screen out the critical contact parameters that had a significant effect on the simulation of the angle of repose. The regression model between the critical contact parameters and the simulated angle of repose was established by the Box-Behnken experimental design, and the critical contact parameters of each powder were optimized based on the regression model. The best combination of critical contact parameters of the extract powder of Guizhi Fuling Capsules was found to be 0.51 for particle-particle static friction coefficient, 0.31 for particle-particle rolling friction coefficient, and 0.64 for particle-stainless steel static friction coefficient. For Paeonol powder, the best combination of critical contact parameters was 0.4 for particle-particle static friction coefficient and 0.19 for particle-particle rolling friction coefficient. The best combination of contact parameters between Paeonol powder and extract powder of Guizhi Fuling Capsules was 0.27 for collision recovery coefficient, 0.49 for static friction coefficient, and 0.38 for rolling friction coefficient. The verification results show that the relative error between the simulated value and the measured value of the angle of repose of the two single powders is less than 1%, while the relative error between the simulated value and the measured value of the angle of repose of the mixed powder with a mass ratio of 1∶1 is less than 4%. These research results provide reliable physical property simulation data for the mixed simulation experiment of extract powder of Guizhi Fuling Capsules and Paeonol powder.

Integrative serum metabolomic analysis for preventive effects of Yaobitong capsule in adjuvant-induced rheumatoid arthritis rat based on RP/HILIC-UHPLC-Q-TOF MS.

Yaobitong capsule (YBTC) has been used for the prevention and treatment of inflammation-related lumbago and leg pain. However, its intervention mechanism still remains unclear. This study was aimed to evaluate the control efficiency of YBTC on adjuvant-induced rheumatoid arthritis (RA) rats by metabonomic method and to explore its possible anti-arthritis mechanism. Taking into account the complexity of endogenous metabolites in serum samples, an integrated metabolomics method based on RP/HILIC-UHPLC-Q-TOF MS was developed, to overcome the limitations of a single chromatographic in this study. The results showed that 32 potential biomarkers of arthritis were identified, primarily related to amino acid metabolism, glucose metabolism, lipid metabolism and nucleotide metabolism. Further receiver operating characteristic analysis revealed that the area under the curve of two down-regulated metabolites (3-Hydroxy-hexadecanoic acid, 2-Oxoarginine) and one up-regulated metabolite (l-Glutamic acid) among 32 biomarkers were 0.906, 0.969 and 1.000, respectively, indicating that high predictive ability of this method for RA. In this study, an integrated serum metabolomics method based on high-resolution mass spectrometry was successfully established for the first time to study the intervention mechanism of YBTC in RA, providing evidence regarding the clinical application of YBTC and a new insight for the prevention of RA in the future.

ASFV pD345L protein negatively regulates NF-κB signalling by inhibiting IKK kinase activity.

The NF-κB pathway is an essential signalling cascade in the defence against viral infections, including African swine fever virus (ASFV) infection. ASFV encodes more than 151 proteins via its own transcription machinery and possesses a great capacity to evade or subvert antiviral innate immune responses. Although some of these viral proteins have been reported, many remain unknown. Here, we show that pD345L, an ASFV-encoded lambda-like exonuclease, acts as an inhibitor of cGAS/STING-mediated NF-κB signalling by blocking the IkappaB kinase (IKKα/ß) activity. Specifically, we showed that overexpression of pD345L suppresses cGAS/STING-induced IFNß and NF-κB activation, resulting in decreased transcription of IFNß and several proinflammatory cytokines, including IL-1α, IL-6, IL-8, and TNFα. In addition, we showed that pD345L acts at or downstream of IKK and upstream of p65. Importantly, we found that pD345L associates with the KD and HLH domains of IKKα and the LZ domain of IKKß and thus interrupts their kinase activity towards the downstream substrate IκBα. Finally, we showed that pD345L-mediated inhibition of NF-κB signalling was independent of its exonuclease activity. Considering these results collectively, we concluded that pD345L blocks IKKα/ß kinase activity via protein-protein interactions and thus disrupts cGAS/STING-mediated NF-κB signalling.

Willingness to accept herpes zoster vaccines and the influencing factors in China.

BACKGROUND: Herpes zoster increases the burden on the elderly in an aging society. Although an effective vaccine licensed by China Food and Drug Administration in 2019 was introduced into the market in June 2020, the willingness and influencing factors of herpes zoster vaccines in Chinese adults ≥ 50-years-old during coronavirus disease-2019 pandemic are yet to be elucidated. METHODS: An online questionnaire survey was conducted using a simple random sampling method in October 2021 for viewers of the broadcast program. A binary logistic regression and multiple response analysis were conducted for herpes zoster vaccine and vaccination willingness. Pareto's graphs were plotted to present the multiple-choice questions of influencing factors. RESULTS: A total of 3838 eligible participants were included in this study. Among them, 43.02% intended to be vaccinated, including 10.34% self-reported about receiving at least one shot of shingles vaccine, 30.22% declined, and 26.76% were hesitant. This population comprised a large proportion of middle-aged and older people (≥ 50-years-old) who have not experienced an episode of herpes zoster (54.98%) or are unaware of the virus (33.22%). The strongest determinants of vaccine hesitancy among older people were education background of Master's degree or above compared to senior high or equivalent and below, personal monthly income < 3000 RMB compared to 3000-5999 RMB, and living in a rural area. CONCLUSIONS: The willingness to get shingles vaccines can be improved further. Professional education and credible recommendation might prompt the elderly to improve their willingness and reassure them of the safety and efficacy of the vaccine. Also, accessibility and affordability should also be improved in the future.

One-step purification and immobilization of thermostable ß-glucosidase on Na-Y zeolite based on the linker and its application in the efficient production of baohuoside I from icariin.

Baohuoside I, a minor flavonoid component of Herba Epimedii, has better bioactivities than its precursor compound icariin. In this work, we have fused the linker (4LP) to thermostable ß-glucosidase (Tpebgl3) and successfully prepared the immobilized enzyme (4LP-Tpebgl3@Na-Y) to produce baohuoside I from icariin. The activity recovery and maximum load of 4LP-Tpebgl3@Na-Y were 95.4% and 50.3 mg/g, respectively. Moreover, it exhibited four-fold improved adsorption selectivity (80.5%) with respect to native enzyme after immobilization. The maximum activity of 4LP-Tpebgl3@Na-Y was exhibited at 85 °C, pH 5.0, and it retained>80% of its initial activity after incubation at 75 °C for 2 h . It showed enhanced tolerance of organic solvent and glucose as compared to free enzymes. Kcat/Km value for 4LP-Tpebgl3@Na-Y was 1616.0 s-1•mM-1, which was 61.0% higher than that of free enzyme. Under suitable conditions (75 °C, pH 5.0, 0.1 U/mL enzyme and 120 min), 2000 mg/L icariin was transformed into baohuoside I with a molar conversion of 97.6%. 4LP-Tpebgl3@Na-Y retained 85.2% of its original activity after 10 cycles of reuse and the 768.8 mg/L/h total productivity of baohuoside I was obtained. This is the first research on one-step purification and immobilization of thermostable ß-glucosidase based on the linker and its application in the efficient production of baohuoside I from icariin.

Genetic analysis of genome sequence characteristics of two lumpy skin disease viruses isolated from China.

BACKGROUND: Lumpy skin disease (LSD) is an acute or subacute infectious disease caused by lumpy skin disease virus (LSDV) of genus Capripoxvirus. The outbreaks of LSD were confirmed in the Yili area of the Xinjiang autonomous region in August 2019 and the Fujian province in June 2020. We detected LSDV in our daily monitoring work, then isolated, identified and sequenced the virus, and analyzed the whole genome characteristics of the isolated strain. RESULTS: Whole genome sequencing revealed that the strains isolated were all LSDV and were named as LSDV XJ201901 and LSDV FJ2019. The results showed that the identity based on whole genome sequences between LSDV XJ201901 and LSDV FJ2019 was 100% and the identity based on whole genome sequences between the two isolated strains and the global LSDV strains was 97.28%-99.99%, with the strain LSDV72/PrachuapKhiriKhan/Thailand/2021 (99.99%) having the highest sequence identity. Analysis of potential recombination events revealed that a total of 18 potential recombination events were identified in strains LSDV XJ201901 and LSDV FJ2019. The two strains are a recombination of Neethling vaccine LW 1959 (GeneBank: AF409138.1) with KSGP 0240 (GeneBank: KX683219.1). It was observed that Neethling vaccine LW 1959 (11/18) and KSGP 0240 (10/18) are involved in most of the potential recombination events. CONCLUSIONS: The virus isolate in this study was LSDV and was identified as a vaccine recombinant strain. The most likely potential parent strains of the two strains in this study are Neethling vaccine LW 1959 and KSGP 0240. The strains in this study are very similar to those isolated in East and Southeast Asia since 2019.

A liquid chromatography-mass spectrometry untargeted urinary metabonomics combined with quantitative analysis of seven amino acids biomarkers on yaobitong capsule in the intervention of rheumatoid arthritis rats.

Yaobitong capsule is a compound preparation of traditional Chinese medicine that has been widely applied in disease treatment. To insight into the therapeutic effects of the yaobitong capsule on rheumatoid arthritis and its mechanisms, a liquid chromatography-mass spectrometry untargeted urine metabolomics method was established and validated, combined with the quantitative analysis of seven potential amino acid biomarkers in rat urine. The results showed that 35 potential biomarkers were found in untargeted metabonomics, which was related to amino acid metabolism, lipid metabolism, energy metabolism, and purine metabolism. Moreover, seven amino acid biomarkers, including proline, methionine, glutamic acid, histidine, lysine, cysteine, and glutamine, were further separated and quantified in multiple-reaction monitoring with a positive ionization mode. Then the linearity, standard curves, accuracy, precision, limit of quantitation, recovery, stability, carryover, and matrix effect of the quantitative method were examined. Finally, the validated method was successfully applied to investigate the urine samples of the control group, adjuvant-induced rheumatoid arthritis model group, yaobitong capsule-treatment group, and positive control group in rats. The contents of seven amino acids in different groups showed significant differences. Consequently, our findings revealed that the yaobitong capsule exerted therapeutic effects on rheumatoid arthritis rats by maintaining amino acid homeostasis.

Grinding edge machining process on small-sized lens module components in a mobile phone.

The periscope phone lens has a bright application prospect; however, the problem of a large chipping size in the grinding process for the periscope phone lens module components seriously limits its development. We address the problem of the large edge chipping size in the grinding process of small-sized module components of periscope mobile phone cameras by investigating the influence of the grinding speed, feed speed, and grinding depth on the chipping size through theoretical simulation analysis and single-factor variable experimental verification. The optimal grinding process parameters were preferred, and yield experiments were conducted using the preferred process parameters. The results show that increasing the grinding speed and decreasing the feed speed and grinding depth can effectively suppress the chipping size of the component grinding edge.