Molecular detection and characterization of Coxiella burnetii in aborted samples of livestock in China.

Coxiella burnetii is the causative agent of zoonotic Q fever. Animals are the natural reservoirs of C. burnetii, and domestic livestock represent the major sources of human infection. C. burnetii infection in pregnant females may causes abortion during late pregnancy, whereby massive shedding of C. burnetii with abortion products becomes aerosolized and persists in the environment. Therefore, monitoring and surveillance of this infection in livestock is important for the prevention of the C. burnetii transmission. Previous serological surveys have shown that C. burnetii infection is endemic in livestock in China. However, few data are available on the diagnosis of C. burnetii as a cause of abortion by molecular methods in livestock. To get a better understanding of the impact of C. burnetii infection on domestic livestock in China, a real-time PCR investigation was carried out on collected samples from different domestic livestock suffering abortion during 2021-2023. A total of 338 samples collected from eight herds of five livestock species were elected. The results showed that 223 (66 %) of the collected samples were positive for C. burnetii DNA using real-time PCR. For the aborted samples, 82 % (128/15) of sheep, 81 % (34/42) of goats, 44 % (15/34) of cattle, 69 % (18/26) of camels, and 50 % (17/34) of donkeys were positive for C. burnetii. Besides, 44 % (8/18) and 4 % (1/25) of asymptomatic individuals of sheep and donkey were also positive for C. burnetii. In addition, the positive samples were further confirmed by amplification and sequencing of the C. burnetii-specific isocitrate dehydrogenase (icd) gene. Phylogenetic analysis based on specific gene fragments of icd genes revealed that the obtained sequences in this study were clustered into two different groups associated with different origin of hosts and geographic regions. This is the first report confirming that C. burnetii exists in aborted samples of sheep, goats, cattle, donkeys and camels in China. Further studies are needed to fully elucidate the epidemiology of this pathogen in livestock as well as the potential risks to public health.

[Effects of different fertilization patterns on soil improvement and vegetation restoration of desertified grassland in northwest Liaoning Province, China]. / 不同培肥模式对辽西北沙化草地土壤改良与植被恢复的影响.

Improving soil fertility is one of the key approaches for ecological restoration of the wind-sand area in northwest Liaoning Province. Taking wind-sand area in northwest Liaoning Province as test object, we conducted a fertilization experiment with treatments of inorganic fertilizer (nitrogen, phosphorus and potassium fertilizers), organic fertilizer, combined application of organic and inorganic fertilizers, and organic fertilizer combined with a biologically organic matrix (γ-polyglutamic acid), and no fertilizer as control. We measured soil organic matter content and extractable cations concentrations, vegetation coverage, and biomass under different fertilization treatments and determine the suitable fertilization mode. The results showed that compared to the control, inorganic fertilizer rapidly increased vegetation coverage and biomass, but high levels of inorganic fertilizer (150 kg N·hm-2) led to soil acidification and Ca2+ leaching. Organic fertilizer increased soil organic matter content, exchangeable K+, Ca2+, and Mg2+ contents, as well as coverage and biomass vegetation, especially combined with γ-polyglutamic acid. Overall, the combination of low levels of inorganic fertilizer (50 kg N·hm-2) and moderate levels of organic fertilizer (30000 kg·hm-2) was the best fertilization practice for the rapid and stable restoration of grassland in wind-sand area. Moreover, the extra addition of γ-polyglutamic acid (60 kg·hm-2)could effectively improve soil fertility.

Short-term legacy effects of long-term nitrogen and water addition on soil chemical properties and micro-bial characteristics in a temperate grassland.

Nitrogen deposition and summer precipitation in eastern Inner Mongolia are predicted to increase in recent decades. However, such increases in nitrogen inputs and precipitation may not be continuous under the future new patterns of global change, with the direction and magnitude of which may change or weaken. The legacy effects of nitrogen and water addition after cessation on ecosystems are still unclear. Based on a 13-year nitrogen and water addition experiment in temperate grassland of northern China, we examined the short-term (2 years) legacy effects of historical nitrogen and water addition on soil physicochemical properties and microbial properties after the cessation of nitrogen and water addition in the 14th year. The results showed that the positive effects of historical nitrogen addition on most of soil nutrient variables diminished after two years of cessation, including ammonium nitrogen, nitrate nitrogen, dissolved organic carbon and nitrogen, and Olsen-P concentrations. In contrast, there were legacy effects on soil microbial characteristics. For example, the historical nitrogen input of 15 g N·m-2·a-1 reduced microbial biomass carbon, respiration, and alkaline phosphomonoesterase activity by 73.3%, 81.9%, and 70.3% respectively. It implied that microbial parameters restored slowly in comparison with soil nutrients, showing a hysteresis effect. Results of Pearson's correlation and redundancy analysis showed that the legacy effects of historical nitrogen addition on microbial parameters could be attributed to the negative effects of nitrogen addition on soil pH. Historical water addition showed significant legacy effects on soil pH, ammonium nitrogen, dissolved organic carbon and nitrogen, respiration, and soil enzyme activities, which significantly interacted with historical nitrogen addition. These results are of great significance to predict the changes in grassland ecosystem functions and services under the local environmental improvement conditions, and to reveal the restoration mechanism of degraded grassland.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Recent updates in click and computational chemistry for drug discovery and development.

Drug discovery is a costly and time-consuming process with a very high failure rate. Recently, click chemistry and computer-aided drug design (CADD) represent popular areas for new drug development. Herein, we summarized the recent updates in click and computational chemistry for drug discovery and development including clicking to effectively synthesize druggable candidates, synthesis and modification of natural products, targeted delivery systems, and computer-aided drug discovery for target identification, seeking out and optimizing lead compounds, ADMET prediction as well as compounds synthesis, hopefully, inspires new ideas for novel drug development in the future.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study.

OBJECTIVE: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. METHODS: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. CONCLUSIONS: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Landscape and progress of global peptide drugs in obstetrics and gynaecology.

Peptides have gained popularity in the global market during recent years and have been placed between small molecule drugs and biologics. However, little is known about the comprehensive landscape of peptide drugs in obstetrics and gynaecology. Herein, we analysed new peptide drug-related clinical trials in obstetrics and gynaecology registered on ClinicalTrials.gov. The number and percentage were used for statistical analysis, and a time trend analysis was conducted by calculating the annual growth rate. We aimed to provide the first overview of the changing landscape and status of global peptide drugs in this prospective field, including exploring drug targets, the cutting-edge oncotherapy of peptide vaccines and peptide-drug conjugates, and unsolved challenges with oral administration.

The progress of peptide vaccine clinical trials in gynecologic oncology.

Peptide vaccine are a type of immunotherapy that are synthesized according to the amino acid sequence of known or predicted tumor antigen epitopes. They are safe and well tolerated and have shown exciting results in gynecologic oncology. However, no peptide vaccine has yet been licensed in this field. This review examines peptide vaccine clinical trials in gynecology registered on ClinicalTrials.gov through January 1, 2022, analyzes the global progress and current achievements of peptide vaccines in gynecology, and explores the efforts focused on devising new methods to boost immunotherapeutic outcomes, including the use of adjuvants, multi-epitope vaccines, combinations of helper T cell epitopes, personalized peptide vaccines, synthetic long peptides, new peptide delivery, and combination therapy.

[Effects of nutrient and water addition on soil inorganic phosphorus fractions in an old-field grassland]. / å »åˆ†å’Œæ°´æ·»åŠ å¯¹å¼ƒè€•è‰åœ°åœŸå£¤æ— æœºç£·ç»„åˆ†çš„å½±å“.

Reasonable nutrient and water management is effective ways to improve productivity and biodiversity of degraded grasslands. However, little is known about the effects of nutrient and water addition on soil inorganic phosphorus (P) fractions in old-field grasslands. Based on a field experiment with nutrient addition (N: 10 g·m-2·a-1, P: 10 g·m-2·a -1) and water addition (180 mm water irrigated during plant growing season) in Duolun County, Inner Mongolia in 2005, we examined the changes of inorganic P fractions and Olsen-P contents in the topsoil (0-10 cm). Results showed that 11-year P addition significantly increased total inorganic P (TIP) content, and that exogenous P was mostly transformed into calcium phosphate (Ca-P: 62.6%-69.2%), and then into aluminium phosphate (Al-P: 19.9%-25.1%), ferric phosphate (Fe-P) and occluded P (O-P). Phosphorus incorporated with nitrogen (N) addition significantly increased Fe-P and Al-P contents by declining soil pH and activating Fe3+ and Al3+ in soil. Water addition alone significantly increased Fe-P, Al-P, and decalcium phosphate (Ca10-P) fractions, and the contents of Fe-P, Al-P, octacalcium phosphate (Ca8-P), and Ca10-P were greater in P incorporated with water treatment than in P addition alone. There was no difference of each inorganic P fraction between P incorporated with N and water treatment and P incorporated with N treatment. Phosphorus and P incorporated with N additions significantly increased soil Olsen-P content, while water addition significantly decreased soil Olsen-P content under P addition alone and P incorporated with N treatment. In the calcareous soils, calcium superphosphate addition could enhance soil inorganic P pool through increasing Ca-P fraction.

[Effects of fertilization and water addition on soil acid neutralizing capacity in an old-field grassland]. / æ–½è‚¥å’Œå¢žæ°´å¯¹å¼ƒè€•è‰åœ°åœŸå£¤é ¸ä¸­å’Œå®¹é‡çš„å½±å“.

Increasing nitrogen (N) deposition results in soil acidification in grasslands. Acid buffering capacity of soil is a critical index evaluating soil acidification, the response of which to N input is regulated by precipitation and concentration of other limiting elements. To explore the responses of soil acidification to N, phosphorus (P), and water inputs, we conducted a 13-year field experiment in an old-field grassland and calculated the acid buffering capacity (ABC) and acid neutralizing capacity (ANC) at the reference of pH=5.0 (ANCpH5.0) and 4.0 (ANCpH4.0), using quadratic curve fitting model. The results showed that, without water addition, single N addition or combined with P addition significantly decreased soil pH, ANCpH5.0 and ANCpH4.0, whereas single P addition had no significant effect on soil pH, ANCpH5.0 or ANCpH4.0. With water addition, the addition of N or combined with P decreased soil pH, ANCpH5.0 and ANCpH4.0, whereas P addition decreased soil pH, increased ANCpH4.0, without effect on ANCpH5.0. In contrast with treatments without water addition, water addition had positive effects on soil pH, ANCpH5.0 and ANCpH4.0. For soils with different initial soil pH values, it was better to select ANC rather than ABC as an index to evaluate soil anti-acidification capacity.

Kartogenin and Its Application in Regenerative Medicine.

Regenerative medicine refers to the possibility of replacing aged/damaged cells with genetically similar young and functional cells to restore or establish normal function. Kartogenin (KGN), a small heterocyclic, drug-like compound was discovered in 2012, which is strongly associated with regenerative medicine. KGN has been applied in many regenerative fields, including cartilage regeneration and protection, tendon-bone healing, wound healing, and limb development. KGN could facilitate cartilage repair, promote formation of cartilage-like transition zone in tendon-bone junctions, stimulate collagen synthesis for wound healing, and regulate limb development in a coordinated manner. Considering the related mechanism, filamin A/CBFß/RUNX1, Ihh, and TGFß/Smad pathways have been reported to involve KGN. Therefore, KGN is proven a promising agent in regenerative medicine; however, studies conducted on the effect of KGN are limited to date and not convictive for long-term use. Further studies are recommended to explore the long-term effect and potential molecular mechanisms of KGN. Our investigations may motivate researchers to expand its applications in different forms and fields.

Cdc45/Mcm2-7/GINS complex down-regulation mediates S phase arrest in okadaic acid-induced cell damage.

Okadaic acid (OA) is one of the most common and widespread marine toxins and causes acute gastrointestinal symptoms known as diarrheic shellfish poisoning (DSP) in humans. Although OA is not classified as a typical neurotoxin, an increasing number of studies have reported its neurotoxic effects. However, most of the available studies have focused on OA-induced inhibition of serine/threonine protein phosphatases, while the molecular mechanism of OA-induced neurotoxicity remains largely unclear. To better understand the potentially toxicological profile of OA, cell cycle arrest, DNA damage and alterations in gene expression in the human neuroblastoma cell line SHSY5Y upon OA exposure were determined using flow cytometry, comet assay, and transcriptome microarray. The results showed that OA could induce cell cycle arrest at S phase and might be involved in significant DNA strand breaks. Gene expression profiling indicated that the differentially expressed genes after OA exposure were significantly enriched in the "DNA replication" and "cell cycle" pathways. Real-time PCR result had further validated that down-regulation of the Cdc45/Mcm2-7/GINS complex might be the major factor regulating those alterations. These findings provide new insight into the molecular mechanisms of OA-induced neurotoxicity, and the current data may also provide a basis for future studies.

Microarray Analysis of Long Noncoding RNAs in Female Diabetic Peripheral Neuropathy Patients.

BACKGROUND/AIMS: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. METHODS: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). RESULTS: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. CONCLUSION: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.

Room-temperature borylation and one-pot two-step borylation/Suzuki-Miyaura cross-coupling reaction of aryl chlorides.

A highly efficient room-temperature borylation strategy of aryl chlorides is described. Utilizing Buchwald's second-generation preformed catalyst, boronate esters were obtained for a wide range of substrates in high yield. The method was also applied to Suzuki-Miyaura cross-coupling reaction in a one-pot two-step sequential manner, providing a facile and convenient access to the direct synthesis of biaryl compounds from aryl chlorides.

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the "neurotrophin-MAPK signaling pathway" was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

Application of distal radius-positioned hinged external fixator in complete open release for severe elbow stiffness.

BACKGROUND: Radical release for severe stiff elbows may lead to instability. Hinged external fixation is used to treat unstable elbows. We hypothesized that extensive open release combined with a distal radius-positioned hinged external fixator would have good performance and low complications rate in treating severe elbow stiffness. Thus, the efficacy and security of this technique were assessed in this study. METHODS: We retrospectively reviewed 38 post-traumatic elbows with severe stiffness that underwent arthrolysis between February 2011 and February 2014. All patients were assessed as having elbow instability after complete arthrolysis. Ligament repair was combined with implantation of a hinged external fixator (fixed to the humerus and distal radius) to maintain elbow stability. Flexion arc, forearm rotation, Mayo Elbow Performance Score, elbow stability, and radiographs were evaluated preoperatively and postoperatively, and complications were documented. RESULTS: Mean follow-up was 31 months. Significant improvement was noted in flexion-extension arc (from 27° to 126°), forearm rotation (from 148° to 153°), and mean Mayo Elbow Performance Score (from 68 points to 96 points). Mean pronation arc decreased from 66° preoperatively to 6° at 1.5 months of follow-up and showed a transient reduction during first 6 months postoperatively. Pin-related infection occurred in 2 patients, which was cured with conservative treatment. Two patients had moderate instability after removal of the fixator and regained stability at the 12-month follow-up. At the last follow-up, complications included ulnar nerve paralysis in 3, recurrence of heterotopic ossification in 1, and moderate pain in 1. CONCLUSIONS: Complete open release combined with a distal radius-positioned hinged external fixator is an effective treatment for severe stiff elbows. This technique had a low complication rate.

Formation and evolution of the unexpected PbI2 phase at the interface during the growth of evaporated perovskite films.

The interface chemistry and evolution of the evaporated perovskite films on ITO, pedot/ITO, Si and glass substrates are studied. As evidenced by X-ray diffraction and X-ray photoemission spectroscopy (XPS) results, the PbI2 phase is found to be inevitably formed at the very initial growth stage, even under the conditions of a MAI-rich environment. The extremely low binding energy of adsorbed MAI particles on all the above substrates, as compared to that of PbI2 particles, is responsible for the presence of the PbI2 phase at the interface. The formation of both hole and electron barriers at the interface of PbI2/MAPbI3, as evidenced by XPS measurements, could block carrier transport into the electrode and thus deteriorate solar cell performance. This result reveals the origin of the poor performance of perovskite solar cells (PSCs) by the vacuum evaporation method, and may help to improve the performance of PSCs made using the vacuum evaporation method.

Histone deacetylase inhibitor reverses multidrug resistance by attenuating the nucleophosmin level through PI3K/Akt pathway in breast cancer.

The development of multidrug resistance (MDR) is the major obstacle in the chemotherapy of breast cancer, and it restricts the application of antitumor drugs in the clinic. Therefore it is urgent to search for ways to reverse MDR and restore sensitivity to chemotherapeutics in breast carcinoma. Currently, histone deacetylase inhibitors (HDACIs) offer a promising strategy for tumor therapy as the effective anticancer drugs. Based on the potential resistant target of nucleophosmin (NPM), the purpose of this study was to explore the reversal effect of a new synthetic histone deacetylase inhibitor, FA17, on MDR in methotrexate-resistant breast cancer cells (MCF-7/MTX) and xenograft tumors. It was shown that the abnormal expression of NPM induced MDR and inhibited downstream mitochondrial apoptotic pathway by activating PI3K/Akt signaling pathway in MCF-7/MTX cells. The reversal effect and molecular mechanism of FA17 were investigated both in vitro and in vivo. We found that FA17 could significantly reverse resistance and sensitize MCF-7/MTX cells to methotrexate. FA17 obviously enhanced resistant cell apoptosis, inhibited expressions of NPM and efflux transporters. Additionally, FA17 could reverse MDR via inactivating PI3K/Akt pathway and accelerating mitochondrial apoptotic pathway both in MCF-7/MTX cells and in xenograft tumors. Taken together, the novel histone deacetylase inhibitor could effectively reverse drug resistance due to suppressing the activity of NPM and drug efflux pumps by PI3K/Akt and mitochondrial apoptotic pathway. The above not only indicated the potential applied value of FA17 in reversing MDR and enhancing the sensitivity of chemotherapy, but also confirmed the role of NPM in the development of MDR in breast cancer.

Visible blind ultraviolet photodetector based on CH3NH3PbCl3 thin film.

We report a prototypical device of CH3NH3PbCl3 film ultraviolet photodetectors that were fabricated with a coplanar metal-semiconductor-metal Au interdigital electrode configuration. Pure phase CH3NH3PbCl3 films with a good crystallinity were formed by a hybrid sequential deposition process featured with inter-diffusion of PbCl2 and CH3NH3Cl upon annealing. The CH3NH3PbCl3 film photodetector exhibits a high responsivity of 7.56 A /W at 360 nm, a ultraviolet/visible rejection ratio (R360 nm/R500 nm) was about two orders of magnitude and fast response speed with a rising time of 170 µs and a decay time of 220 µs. All the above results demonstrate CH3NH3PbCl3 film photodetector as a competitive candidate in the application of visible blind UV detectors.