MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II.

Background and objectives: The differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances. Different radiological criteria may be needed across different stages of the disease. This study aimed to assess the radiological characteristics of MSA-C or SCA 2 patients across various stages of the disease and to identify potential distinguishing factors. Methods: Between January 2000 and January 2020, a total of 390 patients, diagnosed with probable MSA-C according to the second consensus on MSA (317 cases) or with molecularly confirmed SCA 2 (73 cases), who had undergone at least one brain MRI and MRS targeting the cerebellar hemispheres, were enrolled in the study. The clinical parameters and neuroimaging features between these two diseases were compared and analyzed. Results: A greater occurrence of a pontine hot cross bun sign (HCBS), higher scores on the scale for the assessment and rating of ataxia, and reduced levels of cerebellar N-acetyl aspartate (NAA)/creatine (Cr), and cerebellar choline (Cho)/Cr were found in MSA-C patients as compared with SCA 2 patients at similar disease durations. For the patients with an HCBS, a cerebellar Cho/Cr level of <0.53 was indicative of the potential presence of MSA-C, with significant level of specificity (85.96%). Discussion: Discerning SCA2 from MSA-C using MRI and MRS appears to be plausible at various disease stages.

Study on Fine Geological Modeling of Sandstone Reservoir under the Influence of Igneous Rock-A Case of Bohai X Oilfield.

[Purpose] Sandstone reservoirs under the influence of igneous rocks have become some of the most important complex reservoirs. The accurate description of the distribution for this type of reservoir is a major technical problem in hydrocarbon exploration and development. Geological modeling is the fundamental work of reservoir research. However, there is relatively little research on the reservoir modeling of sandstone reservoirs under the influence of igneous rocks. [Method] In this study, taking the Bohai X oilfield as the research object, the distribution characteristics of sandstone reservoirs were characterized, and a quantitative identification method for igneous rocks was established based on seismic, logging, and drilling data. The impact of igneous rocks on sandstone reservoirs was analyzed, and a structural model under a sequence stratigraphic framework was constructed. And then, a three-dimensional geological model of sandstone reservoirs under the influence of igneous rocks was established. [Results] The results show that the physical properties of sandstone reservoirs deteriorate due to the extrusive igneous rocks in the zone with a complex fracture system and the area that volcanic channel developed. After that, referring to the identification and modeling methods of salt domes and using the fine identification and tracking results of volcanic rocks, the volcanic rocks are extracted as attribute bodies, which are finally nested into the geological model. At the same time, according to the influence degree of igneous rocks, a three-dimensional (3D) model was established, which can not only characterize the structure of igneous rocks but also reflect the development of reservoirs. [Conclusions] The research results can better guide the implementation of development wells, avoid reservoir risks, and significantly improve the accuracy of numerical simulation.

GRP78 protein metabolism in obese and diabetic rats: a study of its role in metabolic disorders.

OBJECTIVE: This study aimed to compare and analyze the expression and significance of the GRP78 protein in cochlear cell injury induced by a high glucose and high-fat diet in obese and diabetic rats. METHODS: Male SD rats were randomly divided into two groups: normal (NC) and high-fat (HF) groups. The NC group was fed a standard diet for eight weeks, while the HF group received a high-glucose, high-fat diet. The HF group was further categorized into the obesity group (OB group) and the type II diabetes mellitus group (T2DM group). To induce a type II diabetes mellitus (T2DM) model, the T2DM group received an intraperitoneal injection of a small dose of STZ (45 mg/kg). After four weeks on the original diet, body weight, blood glucose, blood lipid levels, and auditory brainstem response (ABR) thresholds were measured. The cochlea was dissected, and its morphology was observed using HE staining. Immunohistochemistry and western blotting were utilized to examine the expression level of the GRP78 protein in the cochlea. RESULTS: (1) The ABR threshold demonstrated a statistically significant difference between the T2DM group and the OB group (P < 0.05), as well as between the OB group and the NC group (P < 0.05). (2) Based on morphological comparisons from HE-stained sections, the T2DM group exhibited the most significant alterations in the number of cells in the spiral ganglion, the organ of Corti, and the stria vascularis of the cochlea. (3) The expression level of the GRP78 protein in the cochlea was higher in the T2DM group compared to the OB group (P < 0.05) and higher in the OB group compared to the NC group (P < 0.05). CONCLUSION: The findings indicate that the GRP78 protein plays a role in hearing loss caused by T2DM and hyperlipidemia. Moreover, T2DM is more likely than hyperlipidemia to be associated with hearing impairment.

Horizontal gene transfer in activated sludge enhances microbial antimicrobial resistance and virulence.

Activated sludge (AS) plays a vital role in removing organic pollutants and nutrients from wastewater. However, the risks posed by horizontal gene transfer (HGT) between bacteria in AS are still unclear. Here, a total of 478 high-quality non-redundant metagenome-assembled genomes (MAGs) were obtained. >50 % and 5 % of MAGs were involved in at least one HGT and recent HGT, respectively. Most of the transfers (82.4 %) of antimicrobial resistance genes (ARGs) occurred among the classes of Alphaproteobacteria and Gammaproteobacteria. The bacteria involved in the transfers of virulence factor genes (VFGs) mainly include Alphaproteobacteria (42.3 %), Bacteroidia (19.2 %), and Gammaproteobacteria (11.5 %). Moreover, the number of ARGs and VFGs in the classes of Alphaproteobacteria and Gammaproteobacteria was higher than that in other bacteria (P < 0.001). Mobile genetic elements were important contributors to ARGs and VFGs in AS bacteria. These results have implications for the management of antimicrobial resistance and virulence in activated sludge microorganisms.

Retinal safety and toxicity study of artesunate in vitro and in vivo.

Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5µM was safe for IMG cells in vitro. Both 2.5 and 5 â€‹µM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1ß, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 â€‹µM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 â€‹mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 â€‹µM significantly decreased TNF-α gene expression while ART of 100 â€‹µM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 â€‹µM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.

Distinct increase in antimicrobial resistance genes among Vibrio parahaemolyticus in recent decades worldwide.

Vibrio parahaemolyticus is a common pathogen, and has emerged with multiple antimicrobial resistance (AMR). However, few studies have conducted large-scale investigations of AMR and virulence trends of V. parahaemolyticus worldwide. This study longitudinally monitored antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) trends of 1540 V. parahaemolyticus isolates isolated from 1951 to 2021. The number of ARGs in V. parahaemolyticus isolates distinctly increased over the years (P = 5.9e-10), while the number of VFGs decreased significantly (P < 2.2e-16). However, the number of VFGs of isolates isolated from humans has not changed significantly over the years (R = 0.013, P = 0.74), suggesting that the pathogenic risk to humans has not been reduced. Besides, mobile genetic elements are important contributors to ARGs in V. parahaemolyticus (R = 0.34, P < 2.2e-16), but have no promoting effect on VFGs (P = 0.50). The structural equation model illustrated that the human development index promoted the consumption of antibiotics, thereby indirectly promoting an increase in the AMR of the V. parahaemolyticus isolates. Finally, the random forest was performed to predict the ARG and VFG risks of global terrestrial V. parahaemolyticus isolates, and successfully map these threats with over 80% accuracy. This study aimed to evaluate the global risks posed by AMR and virulence, which helps to develop methods specifically targeting V. parahaemolyticus to mitigate these threats.

Predation of Cyclopoid Copepods on the Theronts of Ichthyophthirius multifiliis: Shedding Light on Biocontrol of White Spot Disease.

White spot disease, caused by the parasitic ciliate Ichthyophthirius multifiliis, is a significant threat to the freshwater fish farming industry worldwide, resulting in massive mortality and economic losses. Eliminating the free-swimming theronts from the culture environment is considered crucial for the control of I. multifiliis infection. It is well-documented that planktonic ciliates are valuable food resources for macro-zooplankton in aquatic ecosystems. In this study, we developed a fluorescence labeling method for alive theronts and found that cyclopoid copepods Thermocyclops taihokuensis, Mesocyclops spp., Macrocyclops sp., and Paracyclopina sp. present predation on the theronts in co-culture experiments. Laboratory challenge tests further confirmed that the presence of zooplankton in the culture water body significantly reduced the infection of I. multifiliis in goldfish (p < 0.01). Results from this study revealed that cyclopoid copepods have the potential to be used as biological control agents against white spot disease in aquaculture.

Monitoring Longitudinal Trends and Assessment of the Health Risk of Shigella flexneri Antimicrobial Resistance.

Shigella flexneri infection is the main cause of diarrhea in humans worldwide. The emergence of antimicrobial resistance (AMR) of S. flexneri is a growing public health threat worldwide, while large-scale studies monitoring the longitudinal AMR trends of isolates remain scarce. Here, the AMR gene (ARG) profiles of 717 S. flexneri isolates from 1920 to 2020 worldwide were determined. The results showed that the average number of ARGs in isolates has increased significantly, from 19.2 ± 2.4 before 1970 to 29.6 ± 5.3 after 2010. In addition, mobile genetic elements were important contributors to ARGs in S. flexneri isolates. The results of the structural equation model showed that the human development index drove the consumption of antibiotics and indirectly promoted the antibiotic resistance. Finally, a machine learning algorithm was used to predict the antibiotic resistance risk of global terrestrial S. flexneri isolates and successfully map the antibiotic resistance threats in global land habitats with over 80% accuracy. Collectively, this study monitored the longitudinal AMR trends, quantitatively surveilled the health risk of S. flexneri AMR, and provided a theoretical basis for mitigating the threat of antibiotic resistance.

Two new alkaloids from the endophytic fungus Schizophyllum sp. HM230 isolated from Vincetoxicum mongolicum Maxim.

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M (1) and N (2), along with three known ones (3-5). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1-4 showed middle cytotoxicity against MCF-7 cells with IC50 values range of 68.1 ∼ 87.32 µM. Compounds 1-5 displayed obvious antioxidant activity with the IC50 values range of 0.86 ∼ 5.78 mg/mL.

Neuropeptide Y protects kidney from acute kidney injury by inactivating M1 macrophages via the Y1R-NF-κB-Mincle-dependent mechanism.

Neuropeptide Y (NPY) is produced by the nerve system and may contribute to the progression of CKD. The present study found the new protective role for NPY in AKI in both patients and animal models. Interestingly, NPY was constitutively expressed in blood and resident kidney macrophages by co-expressing NPY and CD68+ markers, which was lost in patients and mice with AKI-induced by cisplatin. Unexpectedly, NPY was renoprotective in AKI as mice lacking NPY developed worse renal necroinflammation and renal dysfunction in cisplatin and ischemic-induced AKI. Importantly, NPY was also a therapeutic agent for AKI because treatment with exogenous NPY dose-dependently inhibited cisplatin-induced AKI. Mechanistically, NPY protected kidney from AKI by inactivating M1 macrophages via the Y1R-NF-κB-Mincle-dependent mechanism as deleting or silencing NPY decreased Y1R but increased NF-κB-Mincle-mediated M1macrophage activation and renal necroinflammation, which were reversed by addition of NPY or by silencing Mincle but promoted by blocking Y1R with BIBP 3226. Thus, NPY is renoprotective and may be a novel therapeutic agent for AKI. NPY may act via Y1R to protect kidney from AKI by blocking NF-κB-Mincle-mediated M1 macrophage activation and renal necroinflammation.

Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups.@*METHODS@#A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions.@*RESULTS@#There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05).@*CONCLUSIONS@#The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Survival results of surgical resection versus CT-guided percutaneous ablation for stage Ⅰnon-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To evaluate the survival results of surgical resection (SR) and CT-guided percutaneous ablation (PA) for stageⅠnon-small cell lung cancer (NSCLC). Methods    The PubMed, Web of Science, EMbase, The Cochrane Library, CNKI, VIP, Wanfang databases from inception to June 2021 were searched to collect comparative studies on the survival results between SR and CT-guided PA treatment for stageⅠNSCLC. RevMan 5.3 software was used for statistical analysis of data. Results    A total of 3 114 patients were included in 11 studies. The results of meta-analysis showed that compared with the PA group, the SR group had a higher 2-year postoperative overall survival (OS) rate (OR=1.44, 95%CI 1.00-2.06, P=0.05), 3-year postoperative OS rate (OR=2.37, 95%CI 1.47-3.81, P<0.001), 5-year OS rate (OR=1.64, 95%CI 1.19-2.28, P<0.01), 5-year progression-free survival rate after operation (OR=2.43, 95%CI 1.54-3.82, P<0.001) and lower local recurrence rate (OR=0.26, 95%CI 0.13-0.54, P<0.001). There were no statistical differences between the two groups in terms of 1-year postoperative OS rate, 1-year, 2-year, and 3-year tumor-related survival rates, 1-year, 2-year tumor-free survival rates, or distant postoperative recurrence rate (P>0.05). Conclusion    For patients with stageⅠNSCLC with optimal basic conditions, surgery is a more appropriate treatment. For patients who cannot withstand surgical injuries or refuse surgery, CT-guided PA is also a potential alternative treatment. However, this conclusion needs  to be verified by prospective controlled trials with larger sample sizes and a more rigorous design.

Dual Activation Strategy to Achieve C-C Cleavage of Cyclobutanes: Development and Mechanism of Rh and Zn Cocatalyzed [4 + 2] Cycloaddition of Yne-Vinylcyclobutanones.

Reported here is the Rh and Zn cocatalyzed [4 + 2] cycloaddition of newly designed yne-vinylcyclobutanones, which can generate 5/6 or 6/6 bicyclic products with an all-carbon quaternary bridgehead center. The reaction has a broad scope and can realize chirality transfer from enantioenriched substrates to the cycloadducts. The key to the success of this [4 + 2] reaction is the introduction of a vinyl group to cyclobutanones, which helps the C-C cleavage of vinylcyclobutanones via oxidative addition. This C-C cleavage step is synergistically aided by Zn coordination to the carbonyl group of vinylcyclobutanones. Of the same importance, visual kinetic analysis and computational studies have been carried out to support the dual activation in the rate-determining C-C cleavage, to derive the rate law of the [4 + 2] reaction, to understand another role of Zn in helping the in situ generation of the cationic Rh catalyst and preventing catalyst deactivation, and to analyze the key transition states and intermediates involved.

Scale for Ocular motor Disorders in Ataxia (SODA).

Eye movements are fundamental diagnostic and progression markers of various neurological diseases, including those affecting the cerebellum. Despite the high prevalence of abnormal eye movements in patients with cerebellar disorders, the traditional rating scales do not focus on abnormal eye movements. We formed a consortium of neurologists focusing on cerebellar disorders. The consortium aimed to design and validate a novel Scale for Ocular motor Disorders in Ataxia (SODA). The primary purpose of the scale is to determine the extent of ocular motor deficits due to various phenomenologies. A higher score on the scale would suggest a broader range of eye movement deficits. The scale was designed such that it is easy to implement by non-specialized neurological care providers. The scale was not designed to measure each ocular motor dysfunction's severity objectively. Our validation studies revealed that the scale reliably measured the extent of saccade abnormalities and nystagmus. We found a lack of correlation between the total SODA score and the total International Cooperative Ataxia Rating Scale (ICARS), Scale for Assessment and Rating of Ataxia (SARA), or Brief Ataxia Rating Scale (BARS). One explanation is that conventionally reported scales are not dedicated to eye movement disorders; and when present, the measure of ocular motor function is only one subsection of the ataxia rating scales. It is also possible that the severity of ataxias does not correlate with eye movement abnormalities. Nevertheless, the SODA met the consortium's primary goal: to prepare a simple outcome measure that can identify ocular motor dysfunction in patients with cerebellar ataxia.

[Radiation-Induced Heart Disease: Current Status and Challenges].

Being one of the major therapeutic measures for malignant tumors, radiation therapy, or radiotherapy, plays a particularly crucial role in the multidisciplinary integrated treatment of thoracic tumors. With the development in radiotherapy technology, the research focus has shifted from improving the overall survival of malignant tumor patients to reducing the incidence of radiation-related injuries. Currently, radiation-induced heart disease (RIHD) has become one of the leading non-cancer causes of death in thoracic tumor patients who have undergone radiotherapy, seriously affecting their quality of life and clinical prognosis. In recent years, there has been growing understanding of the pathogenesis of RIHD, and proposals have been made for some potential measures for the prevention and treatment of RIHD. Based on the clinical manifestations and pathological changes of RIHD that have been reported, we herein reviewed the biological mechanism and potential treatment options for RIHD. We also discussed existing challenges in the prevention and treatment of RIHD, intending to provide references for the prevention and treatment of RIHD.

The erection of a new genus, Neotegorhynchus n. g. (Palaeacanthocephala, Illiosentidae), with a redescription of Neotegorhynchus cyprini n. comb. from Cyprinus carpio from the Yangtze River basin, China.

The present paper summarizes acanthocephalan parasites of the family Illiosentidae Golvan, 1960, collected from the intestine of common carp (Cyprinus carpio L.) from Taihu Lake in Wuxi, Jiangsu Province, China. A total of 21 acanthocephalan specimens were found in 6 carps (prevalence of 35%). All the studied specimens were assigned to the family Illiosentidae based on the family-specific morphology of the worms and the presence of 8 cement glands in the males. However, the specimens recently found in common carp differed from all 14 extant genera of the family Illiosentidae in the structure of the reproductive system of both sexes, i.e. i) a vagina lacking a muscular sphincter; ii) the presence of a terminally pointed protruding tail end in the form of a dome with a muscular base; iii) the female genital muscles are fan-shaped cells, each of which has a nucleus and is not attached to the anterior wall of the body; iv) the muscular lip of the bursa of males repeats the curved shape of the posterior end of females, which en copula allows the lip of the bursa to seal to the posterior end of the female. Morphologically Neotegorhynchus n. g. is closest to the genus Tegorhynchus, but differs from it, in addition above features in i) the terminal position of the genital pores of females without a hollow genital vestibule and without a transverse cleft connected to the dorsal terminal genital pore, as in Tegorhynchus brevis; ii) cerebral ganglion at the border of the anterior and middle third of the proboscis vessel; iii) spherical cement reservoir. Molecular studies confirmed Neotegorhynchus n. g. as belonging to the family Illiosentidae, showing less than 98.9% sequence similarity in SSU rDNA and 81.8% in COI with the genus Dentitruncus. Therefore, a new acanthocephalan genus, Neotegorhynchus n. g., is erected, and Neotegorhynchus cyprini n. comb. is designated as the type species and its neotype.

Characterization of the complete mitochondrial genome of Nippotaenia mogurndae Yamaguti and Miyata, 1940 (Cestoda: Nippotaeniidae).

In this study, we report the first complete mitochondrial genome of the tapeworm Nippotaenia mogurndae in the order Nippotaeniidea Yamaguti, 1939. This mitogenome, which is 14,307 base pairs (bp) long with an A + T content of 72.2%, consists of 12 protein-coding genes, 22 transfer RNA (tRNA) genes, two rRNA genes, and two non-coding regions. Most tRNAs have a conventional cloverleaf structure, but trnS1 and trnR lack dihydrouridine arms of tRNA. The two largest non-coding regions, NCR1 (220 bp) and NCR2 (817 bp), are located between trnY and trnS2 and between nad5 and trnG, respectively. Phylogenetic analyses of mitogenomic data indicate that N. mogurndae is closely related to tapeworms in the order Cyclophyllidea.

Carotane sesquiterpenoids A-G from the desert endophytic fungus Fusarium sp. HM 166.

Seven undescribed carotane sesquiterpenoids named fusanoids A-G (1-7), along with one known analog (8) and two known sesterterpenes (9 and 10), were isolated from the fermentation broth of the desert endophytic fungi Fusarium sp. HM166. The structures of the compounds, including their absolute configurations, were determined by spectroscopic data, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 10 showed cytotoxic activities against human hepatoma carcinoma cell line (Huh-7) and human breast cell lines (MCF-7 and MDA-MB-231), and compound 2 showed cytotoxic activity against MCF-7, while compounds 4-9 were inactive against all the tested cell lines. Compounds 4 and 10 showed potent inhibitory activities against the IDH1R132h mutant.