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• SOX9 transactivates FGF1, PDGFα, and TGF-β1 in C5b-9-attacked mesangial cells. • ERK1/2 phosphorylate SOX9, which enhances SOX9-mediated transactivation. • Inhibition ERK1/2 activation attenuates glomerular damage in Thy-1 nephritis. • Silencing ERK1/2 or SOX9 gene ameliorates glomerular injury in Thy-1 nephritis. Mesangial proliferative glomerulonephritis (MsPGN) and its related rat model Thy-1 nephritis (Thy-1N) are associated with C5b-9 deposition and are characterized by proliferation of glomerular mesangial cell (GMC) and expansion of extracellular matrix (ECM) expansion, alongside overexpression of multiple growth factors. Although fibroblast growth factor 1 (FGF1), platelet-derived growth factor alpha (PDGFα), and transforming growth factor beta 1 (TGF-β1) are well known for their proproliferative and profibrotic roles, the molecular mechanisms responsible for regulating the expression of these growth factors have not been thoroughly elucidated. In this study, we found that sublytic C5b-9 induction of sex-determining region Y-box 9 (SOX9) transactivated FGF1, PDGFα, and TGF-β1 genes in GMCs, resulting in a significant increase in their mRNA and protein levels. Besides, sublytic C5b-9 induction of activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylated SOX9 at serine 181 and serine 64, which enhanced SOX9′s ability to transactivate FGF1, PDGFα, and TGF-β1 genes in GMCs. Furthermore, we demonstrated that inhibiting ERK1/2 activation or silencing either ERK1/2 or SOX9 gene led to reduced SOX9 phosphorylation, decreased generation of FGF1, PDGFα, and TGF-β1, and ameliorated glomerular injury in rat Thy-1N. Overall, these findings suggest that expression of FGF1, PDGFα, and TGF-β1 is promoted by ERK1/2-mediated phosphorylation of SOX9, which may provide a valuable insight into the pathogenesis of MsPGN and offer a potential target for the development of novel treatment strategies for MsPGN. [ABSTRACT FROM AUTHOR]

The occurrence of the underwater suction vortex will cause the ship to vibrate violently and even lose thrust. The evolution process of the underwater suction vortex was obtained by high-speed photography. According to the characteristics of vortex in different phases, its diachronic process can be divided into five phases: premonitory, nascent, developing, weakening, and disappearing. The underwater suction vortex is a vertical axis vortex below the intake, and its shape is similar to a tornado, showing a form of thick at the top and thin at the bottom. The pressure fluctuation test studied the time-frequency characteristics of pressure fluctuation induced by the underwater suction vortex. The results show that the underwater suction vortex can cause the pressure fluctuation amplitude to recover after a sudden drop. The frequency of characteristic low frequency induced by the underwater suction vortex is 0.28 Hz, which is easy to be ignored. The corresponding amplitude of this frequency is much larger than that of other frequencies, and the low-frequency pressure fluctuation induced by the underwater suction vortex is dominant. The results can provide a theoretical basis for the mechanism and prevention of suction vortex of water jet propulsion pump unit. • The hydraulic performance experimental system of the water jet propulsion pump unit is designed. • The high-speed photography and pressure fluctuation experimental procedure and data acquisition method are presented. • The temporal and spatial evolution characteristics of the underwater suction vortex are obtained by high-speed photography. • The time-frequency characteristics of the pressure fluctuation induced by the underwater suction vortex are obtained. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has proven to be an urgent threat to human health. Proteomics (TMT/LC-MS/MS) and bioinformatics approaches were employed to explore the potential mechanisms underlying carbapenem resistance. Proteomic profiling of CRKP and susceptible KP (sKP) isolates revealed the involvement of outer membrane, beta-lactam resistance pathway, and two-component systems (TCSs) in carbapenem resistance. 27 CRKP strains and 27 susceptible Klebsiella pneumoniae strains were isolated from inpatients at the Second Xiangya Hospital, China to verify the mechanisms. Modified carbapenem inactivation method (mCIM) and PCR of common carbapenem resistance genes confirmed that 77.8% (21/27) of CRKP isolates were carbapenemase-producing. Porin decrease in CRKP isolates was found by SDS-PAGE and mRNA levels of major porins (OmpK35 and OmpK36). RT-qPCR detection of two-component systems (envZ , ompR , phoP , phoQ , baeS and baeR) revealed down-regulation of EnvZ-OmpR, PhoPQ, BaeSR TCSs. Expression of the TCSs, except ompR, were closely correlated with OMPs with the R-value >0.7. Together, this study reaffirmed the significance of the β-lactam resistance pathway in CRKP based on proteomic analysis. OmpK35/36 porin reduction and the controversial downregulation of EnvZ-OmpR, PhoPQ, and BaeSR TCSs were confirmed in carbapenem resistance of Klebsiella pneumoniae. • Proteomic profiling revealed that outer membrane, beta-lactam resistance pathway and two-component systems are involved in carbapenem resistance. • Reduced expression of porins is common in carbapenem resistance. • Carbapenem resistance was associated with decreased expression of EnvZ-OmpR, PhoPQ, and BaeSR two-component systems. • The mRNA levels of two-component systems positively correlated with those of porins. [ABSTRACT FROM AUTHOR]

To explore the clinical features, fetal outcomes and serum bile acids (BAs) metabolism in asymptomatic hypercholanemia of pregnancy (AHP), as well as the comparison with those in intrahepatic cholestasis of pregnancy (ICP) and normal pregnancies. A study containing 676 pregnant women was performed to investigate the clinical informations, routine biochemical features and obstetric outcomes of AHP by the comparison with ICP and normal pregnancies. Within the study subjects, 203 pregnant women received prospective determination for 55 serum individual BAs based on a validated UPLC-QTOF-MS/MS method. The differences in clinical features and serum BAs metabolism among the three groups were then investigated. The risk of adverse fetal outcomes in AHP (28.3%) was significantly higher than that in normal pregnancies (8.9%, p < 0.001), but lower than that in ICP group (52.1%, p < 0.001). Multivariate statistics analysis indicated a distinctive serum BAs metabolic profiling among the three groups (PLS-DA, R2Y = 0.580, Q2 = 0.537). Levels of serum BAs especially for deoxycholic acid species were found remarkably elevated in AHP as compared to those in ICP. AHP group had distinguished clinical features and serum BAs metabolism as compared to ICP group and normal pregnancies. • AHP women suffered from hypercholanemia approximately five weeks earlier than ICP patients. • The risk of adverse fetal outcomes in AHP was significantly higher than that in normal pregnancies, but lower than that in ICP group. • AHP had distinctive serum BAs metabolic profiling from both ICP and normal pregnancies. • Levels of serum deoxycholic acid species were found remarkably elevated in AHP. [ABSTRACT FROM AUTHOR]

● Sulfur atoms are covalently linked with TiO 2 nanodots. ● S-TiO 2 nanodots are embedded in N-doped carbon nanofibers. ● S-TiO 2 /C can provide additional faradaic pseudocapacitance. ● The long-term stability (no decay after 10000 cycles at 5 A g−1) is achieved. Sodium ion capacitors (SICs) have attracted extensive attention due to their combination of high-power electric-double-layer capacitors (EDLCs) and high-energy sodium ion batteries (SIBs). However, development of high-performance SIHCs has been plagued by the lack of superior Na+-storage anode materials to couple with the activated carbon (AC) cathode. In this work, we have prepared a sulfur-enriched self-supported TiO 2 /C nanofiber membrane using a simple and scalable electrospinning technique. In such S-TiO 2 /C structure, sulfur atoms (13%) are covalently linked with TiO 2 nanodots (5–10 nm), which are homogeneously embedded in highly conductive N-doped carbon nanofibers. Chemically bonded sulfur can not only provide additional faradaic pseudocapacitance but also show robust structural stability. In terms of sodium storage performance, the as-made S-TiO 2 /C electrode exhibits high reversible capacity (410 mAh g‒1 at 0.1 A g‒1), high rate capability (173 mAh g‒1 at 15 A g‒1), and ultralong cycle life (no capacity degradation after 10000 cycles). When coupling with the AC cathode, the SIC full cell is capable of delivering high energy and power densities as well as long cycle life. Sulfur atoms covalently linked with TiO 2 nanodots (5–10 nm) are homogeneously embedded in highly conductive N-doped carbon nanofibers, which can not only provide additional faradaic pseudocapacitance but also enable the fast transport transfer of electrons and Na+ ions. [Display omitted] [ABSTRACT FROM AUTHOR]

Resveratrol has been found to improve ethanol-induced diabetes. Although pancreatic β-cell senescence-induced β-cell mass loss plays a critical role in the progression of diabetes, the exact mechanism by which resveratrol improves ethanol-triggered β-cell senescence and its role in ethanol-induced diabetes remains unknown. Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 2.4 g/kg·bw ethanol with or without 100 mg/kg·bw resveratrol for 22 weeks. Resveratrol decreased the ethanol-induced augmentation in senescence-associated β-galactosidase (SA-β-gal)-positive area and attenuated reduction in β-cell mass, which were based on elevated levels of SIRT1 and proliferation marker Ki67 and reduced levels of senescence-associated markers (p-p38MAPK and p16INK4a). Similarly, resveratrol rescued the reduction in NAD+/NADH ratio and SIRT1 and inhibited the upregulation of p-p38MAPK and p16INK4a in ethanol-treated INS-1 cells. Furthermore, supplementation with NAD+ inducer nicotinamide mononucleotide, SIRT1 activator SRT1720 or p38MAPK inhibitor SB203580 effectively reversed ethanol-induced β-cell senescence, while supplementation with SIRT1 inhibitor Ex527 or NAD+ inhibitor FK866 abrogated resveratrol-mediated antisenescence effects in INS-1 cells. Together, our results indicate that resveratrol improves ethanol-triggered β-cell senescence and consequently recovers β-cell mass loss by inhibiting p38MAPK/p16 pathway through an NAD+/SIRT1 dependent pathway. [ABSTRACT FROM AUTHOR]

• Spot urine samples were analyzed by HPLC-FD/VWD. • Detection of metanephrines, 3-methoxytyramine and creatinine(Cr) simultaneously. • Peak area ratios of analytes to Cr for the diagnosis of pheochromocytoma. • As the use of Cr (internal reference), no need for exogenous IS and standard curves. • The diagnostic method is simple, low-cost and with superior diagnostic performance. Detection of normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT) could be used to diagnose pheochromocytomas and paragangliomas (PPGLs). The accuracy for the diagnosis of PPGLs is only 6% by virtue of the classic symptom triad. In addition, false-positive results were found using plasma free MNs as biomarkers. Spot urinary free metanephrines (MNs) presented high specificity for PPGLs diagnosis in our previous work by HPLC with the electrochemical detection. Whereas, MNs and creatinine (Cr) need to be detected separately. A simple and specific method was urgently needed for the diagnosis of PPGLs. Here, we established a new HPLC method for spot urinary free MNs and 3-MT by the fluorescence detection and Cr by the ultraviolet detection simultaneously. It was worth mentioning that Cr for the virtue of being fairly constant in a given subject was used as an internal reference correction to eliminate the effect of spot urine volume for the diagnosis of PPGLs. Thirty-seven patients with PPGLs and 164 control subjects were detected by the established method and the peak area ratios of MNs and 3-MT to Cr were used innovatively for the diagnosis of PPGLs. The results showed acceptable precisions and recoveries. The sensitivities of the method were 94.6%, 91.9% and 86.5% and the specificities were 96.3%, 93.9% and 82.3%, respectively by the peak area of NMN/Cr, MN/Cr and 3-MT/Cr for the diagnosis. The established method provides a promising way for simple, rapid and accurate diagnosis of PPGLs. [ABSTRACT FROM AUTHOR]

• The reflection wave is the predominant factor that leads to air-entrainment in pump sump. • The vertical pressure gradient plays a negative role, while the streamwise and spanwise pressure gradients reinforce the dimples and waves. • The air-entrainment formation process for steady and unsteady cases are revealed from the perspective of wave and dimple motions. Air-entrainment is a negative phenomenon in pump stations. The process and the underlying mechanism are far from being fully understood. Based on the previous research, the present paper numerically studies the air-entrained vortex formation in a benchmark pump sump. The bifurcation model (BM) for capturing the rotating characteristics of the vortex and the simple coupled level set and volume of fluid method (S-CLSVOF) for tracking the free surface are adopted in this study. During both steady (case 1) and unsteady (case 2) air-entrained vortex formations, it is found that the wave is the predominant aspect. Exploration on the pressure signals reveals that the wave is generated by the reflection effect of the back wall and propagates from downstream to upstream. The vertical pressure gradient plays a negative role, rather than a positive one as expected. The streamwise and spanwise pressure gradients are found to drive the dimples and waves. The processes of the air-entrained vortex formations in two cases are analyzed in detail. For case 1, the formation process is wavy – inception – propagation – steady – fully developed. For case 2, there are some differences including the collision and reformation stages. Two waves will collide with each other after the inception and reform near the pipe. The process is wavy/inception – collision – reformation – propagation – fully developed. The study offers a new perspective on the air-entrainment mechanism. Accounting for the wavy characteristics, it is expected to eliminate the air-entrained vortex by suppressing the reflection wave. [ABSTRACT FROM AUTHOR]

Glutamatergic dysregulation has served as one common pathophysiology of major depressive disorder (MDD) and a promising target for treatment intervention. Previous studies implicate neurotransmission via metabotropic glutamate receptors (mGluRs) and Homer1 in stress-induced anhedonia, but the mechanisms have not been well elucidated. In the present study, we used two different animal models of depression, chronic social defeat stress (CSDS) and chronic restraint stress (CRS), to investigate the expression of Homer1 isoforms and functional interaction with mGluRs. We found that chronic stress selectively upregulated the expression of Homer1b/c in the hippocampus, whereas the level of Homer1a was unchanged. Additionally, there was a significant negative correlation between the levels of Homer1-mGluR5 signaling and depressive-like behaviors. Both application of paired-pulse low-frequency stimulation (PP-LFS) and the selective group 1 mGluRs agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) significantly enhanced mGluR-dependent long-term depression (LTD) at CA3-CA1 pyramidal cell synapses in slices from susceptible mice, whereas there was no change in NMDAR-dependent LTD induced by LFS. Furthermore, these effects were associated with the internalization of surface AMPARs in hippocampal pyramidal neurons, including reduced the expression of AMPARs and amplitude of AMPARs-mediated mEPSC. Finally, we found that chronic stress activated the KR-like ER kinase-eukaryotic initiation factor 2α (PERK-eIF2α) signaling pathway, subsequently phosphorylated cAMP response element binding protein (CREB) at the S129 and reduced the BDNF level, eventually leading to the impairment of synaptic transmission and depressive-like behaviors. Therefore, our study suggests that PERK-eIF2α acts as a critical target downstream of Homer1-mGluR5 complex to mediate chronic stress-induced depressive-like behaviors, and highlights them as a potential target for the treatment of mood disorder. • Chronic stress increases Homer1-mGluR5 levels in the hippocampus of mice. • CSDS enhances hippocampal mGluR-dependent long-term depression (mGluR-LTD) via the internalization of surface AMPARs. • PKR-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) phosphorylation facilitates mGluR-LTD induced by CSDS. [ABSTRACT FROM AUTHOR]

A photo-induced electron donor-acceptor (EDA) complex enabled tandem reaction of alkyne ketones via a radical difluoroalkylation/cyclization cascade sequence is reported. The EDA complex plays a key role, and the C - Br bond homolysis process may also be involved for this transformation. Varieties of difluoroalkyl-substituted thiofavones can be smoothly assembled in moderate to good yields under photocatalyst-, metal- and oxidant-free conditions, thus offering potential applications for pharmaceutical research.

Structural variants (SVs) significantly contribute to human genome diversity and play a crucial role in precision medicine. Although advancements in single-molecule long-read sequencing offer a groundbreaking resource for SV detection, identifying SV breakpoints and sequences accurately and robustly remains challenging. We introduce VolcanoSV, an innovative hybrid SV detection pipeline that utilizes both a reference genome and local de novo assembly to generate a phased diploid assembly. VolcanoSV uses phased SNPs and unique k-mer similarity analysis, enabling precise haplotype-resolved SV discovery. VolcanoSV is adept at constructing comprehensive genetic maps encompassing SNPs, small indels, and all types of SVs, making it well-suited for human genomics studies. Our extensive experiments demonstrate that VolcanoSV surpasses state-of-the-art assembly-based tools in the detection of insertion and deletion SVs, exhibiting superior recall, precision, F1 scores, and genotype accuracy across a diverse range of datasets, including low-coverage (10x) datasets. VolcanoSV outperforms assembly-based tools in the identification of complex SVs, including translocations, duplications, and inversions, in both simulated and real cancer data. Moreover, VolcanoSV is robust to various evaluation parameters and accurately identifies breakpoints and SV sequences., (© 2024. The Author(s).)

Background: Spatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remains challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of comprehensive benchmark studies complicates the selection of methods and future method development., Results: In this study, we systematically benchmark a variety of state-of-the-art algorithms with a wide range of real and simulated datasets of varying sizes, technologies, species, and complexity. We analyze the strengths and weaknesses of each method using diverse quantitative and qualitative metrics and analyses, including eight metrics for spatial clustering accuracy and contiguity, uniform manifold approximation and projection visualization, layer-wise and spot-to-spot alignment accuracy, and 3D reconstruction, which are designed to assess method performance as well as data quality. The code used for evaluation is available on our GitHub. Additionally, we provide online notebook tutorials and documentation to facilitate the reproduction of all benchmarking results and to support the study of new methods and new datasets., Conclusions: Our analyses lead to comprehensive recommendations that cover multiple aspects, helping users to select optimal tools for their specific needs and guide future method development., (© 2024. The Author(s).)

Background: We investigated the presence of Chlamydia psittaci in poultry and the environment in live poultry wholesale markets in Changsha during 2021-2022 and conducted a phylogenetic analysis to understand its distribution in this market., Methods: In total, 483 samples were analyzed using real-time polymerase chain reaction and 17 C. psittaci-positive samples using high-throughput sequencing, BLAST similarity, and phylogenetic analysis., Results: Twenty-two out of 483 poultry and environmental samples were positive for C. psittaci (overall positivity rate: 4.55%) with no difference in positivity rates over 12 months. Chlamydia psittaci was detected at 11 sampling points (overall positivity rate: 27.5%), including chicken, duck, and pigeon/chicken/duck/goose shops, with pigeon shops having the highest positivity rate (46.67%). The highest positivity rates were found in sewage (12.5%), poultry fecal (7.43%), cage swab (6.59%), avian pharyngeal/cloacal swab (3.33%), and air (2.29%) samples. The ompA sequences were identified in two strains of C. psittaci, which were determined to bear genotype B using phylogenetic analysis. Thus, during monitoring, C. psittaci genotype B was detected in the poultry and environmental samples from the poultry wholesale market in Changsha., Conclusions: To address the potential zoonotic threat, C. psittaci monitoring programs in live poultry markets should be enhanced., (© 2024. The Author(s).)

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C 2 - or C 1 -symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies., (© 2024. The Author(s).)

Long-read sequencing offers long contiguous DNA fragments, facilitating diploid genome assembly and structural variant (SV) detection. Efficient and robust algorithms for SV identification are crucial with increasing data availability. Alignment-based methods, favored for their computational efficiency and lower coverage requirements, are prominent. Alternative approaches, relying solely on available reads for de novo genome assembly and employing assembly-based tools for SV detection via comparison to a reference genome, demand significantly more computational resources. However, the lack of comprehensive benchmarking constrains our comprehension and hampers further algorithm development. Here we systematically compare 14 read alignment-based SV calling methods (including 4 deep learning-based methods and 1 hybrid method), and 4 assembly-based SV calling methods, alongside 4 upstream aligners and 7 assemblers. Assembly-based tools excel in detecting large SVs, especially insertions, and exhibit robustness to evaluation parameter changes and coverage fluctuations. Conversely, alignment-based tools demonstrate superior genotyping accuracy at low sequencing coverage (5-10×) and excel in detecting complex SVs, like translocations, inversions, and duplications. Our evaluation provides performance insights, highlighting the absence of a universally superior tool. We furnish guidelines across 31 criteria combinations, aiding users in selecting the most suitable tools for diverse scenarios and offering directions for further method development., (© 2024. The Author(s).)

Background: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI., Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022., Results: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I 2  = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I 2  = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I 2  = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants., Conclusions: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes., (© 2024. Springer Nature Switzerland AG.)

Purpose: The purpose of this study is to identify the associated factors of two types of lichenoid vulvar disease (LVD) and to compare the differences in related factors between the different pathological types of lichenoid vulvar disease (LVD)., Methods: The study conducted at the West China second Hospital of Sichuan University included a total of 1770 patients with biopsy-confirmed vulvar lichen simplex chronicus (VLSC)and vulvar lichen sclerosus(VLS), along with 1209 patients with normal vulvovagina as control. Further pathological subtype analysis was carried out on 163 cases of vulvar lichen simplex chronicus and 51 cases of vulvar lichen sclerosus. In addition, Univariate chi-square test and multivariate logistic regression were used to analyze the lichenoid vulvar disease group and vulvovaginal normal control group., Results: Univariate analysis revealed that there were statistically significant differences (P < 0.05) in factors between the LVD group and the control group, except for living type, sleep habit, history of drinking, and allergic diseases. There was no significant difference in late sleep, spicy diet, and coffee intake in the factors of life and eating habits and the concomitant disease factors. Furthermore, univariate analysis showed that except for eating seafood, humid living environment, residence, caffeinated drinks, hypertension, and vaginitis, there were statistical differences in the related factors of LVSC., Conclusion: The incidence about lichenoid vulvar disease is influenced by various factors such as dietary habits, living environment, mental stress, concomitant diseases, hormone levels and so on, and there were no significant differences in these factors between VLS and VLSC except for income, work stress, systemic immune diseases, and menopause., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

We conducted a cross-sectional study using an online questionnaire to investigate the current status of urinary tract infections (UTIs) and the use of clean intermittent catheterization (CIC) in Chinese community-based SCI patients and to explore the risk factors for UTIs in patients using CIC. Our findings suggest that the prevalence of UTIS is higher in Chinese community-based SCI patients compared with patients in medically developed countries. In addition, we found that CIC had the lower incidence of UTIs than urinary indwelling catheter (UIC) and suprapubic catheter (SPC), and that SCI patients with CIC had low rates of use and poor compliance. Further analysis indicated that most of the risk factors for UTIs in CIC patients were associated with irregular use of CIC. Therefore, we call for not only the need to provide stronger caregiver support and financial assistance to improve CIC adherence in Chinese community SCI patients, but also the establishment of a database of Chinese SCI patients in order to enhance the management of bladder emptying methods and further standardize the CIC operation in such patients, thus reducing the risk of UTIs in Chinese community SCI patients., (© 2023. Springer Nature Limited.)

The effects of heterogenous (anaerobic sludge from treating distillery sewage, ASDS) and homologous (anaerobic sludge from treating swine wastewater, ASSW) inocula on anaerobic digestion and the microbial community in an up-flow anaerobic sludge blanket treating swine wastewater were compared. The highest chemical oxygen demand removal efficiencies with ASDS (84.8%) and ASSW (83.1%) were obtained with an organic loading rate of 15 kg COD/m 3 /d. For ASSW compared with ASDS, methane production efficiency was 15.3% higher and excess sludge production was 73.0% lower. The abundance of the cellulose hydrolyzing bacterium Clostridium sensu stricto&#95;1 with ASDS (36.1%) was 1.5 times that with ASSW, while that of Methanosarcina with ASSW (22.9%) was > 100 times that with ASDS. ASDS reduced the content of pathogenic bacteria by 88.0%, while ASSW maintained a low level of pathogenic bacteria. ASSW greatly improved the methane production efficiency of wastewater and is more suitable for treating swine wastewater., 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 © 2023 Elsevier Ltd. All rights reserved.)

Purpose: We aimed to evaluate the in vitro antibacterial effects of combination of cefepime/avibactam against carbapenem-resistant Klebsiella pneumonia (CRKP) and explore the resistance mechanism of FEP/AVI., Patients and Methods: This study explored the in vitro antibacterial activities of ceftazidime/avibactam (CAZ/AVI) and cefepime/avibactam (FEP/AVI) against 40 and 76 CRKP clinical isolates. Proteomics and metabolomics were employed to investigate the resistance mechanisms of CRKP to FEP/AVI., Results: FEP/AVI (MIC 50 /MIC 90 0.5/4-64/4 μg/mL, resistance rate 17.1%) showed better antibacterial activity against CRKP than CAZ/AVI (MIC 50 /MIC 90 4/4-128/4 μg/mL, resistance rate 20%) in vitro. Bioinformatics analysis showed that the differentially expressed proteins (DEPs) were enriched in alanine, aspartate and glutamate metabolism, and ribosome. Remarkably, transcriptional and translational activity-related pathways were inhibited in FEP/AVI resistant CRKP. Overlap analysis suggested that H-NS might play an important role in resistance to FEP/AVI in CRKP. The mRNA levels of DEPs-related genes ( adhE, gltB, purA, ftsI and hns ) showed the same trends as DEPs in FEP/AVI susceptible and resistant strains. FEP/AVI resistant isolates demonstrated stronger biofilm formation capacity than susceptible isolates. Metabolomics results showed that disturbed metabolites were mainly lipids, and adenine was decreased in FEP/AVI resistant CRKP., Conclusion: These results indicated that H-NS, GltB and SpoT may directly or indirectly promote biofilm formation of CRKP and led to FEP/AVI resistance, but inhibited ribosomal function. Our study provides a mechanistic insight into the acquisition of resistance to FEP/AVI in Klebsiella pneumoniae ., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 Wen et al.)

Background: Schistosomiasis is a water-borne parasitic disease estimated to have infected >140 million people globally in 2019, mostly in sub-Saharan Africa. Within the goal of eliminating schistosomiasis as a public health problem by 2030 in the World Health Organization (WHO) Roadmap for neglected tropical diseases, other regions cannot be neglected. Empirical estimates of the disease burden in Southeast Asia largely remain unavailable., Methods: We undertook a systematic review to identify empirical survey data on schistosomiasis prevalence in Southeast Asia using the Web of Science, ScienceDirect, PubMed and the Global Atlas of Helminth Infections, from inception to 5 February 2021. We then conducted advanced Bayesian geostatistical analysis to assess the geographical distribution of infection risk at a high spatial resolution (5 × 5 km) using the prevalence, number of infected individuals and doses needed for preventive chemotherapy., Results: We identified 494 Schistosoma japonicum surveys in the Philippines and Indonesia, and 285 in Cambodia and Laos for S. mekongi. The latest estimates suggest that 225 [95% credible interval (CrI): 168-285] thousand in the endemic areas of Southeast Asian population were infected in 2018. The highest prevalence of schistosomiasis was 3.86% (95% CrI: 3.40-4.31) in Laos whereas the lowest was 0.29% in Cambodia (95% CrI: 0.22-0.36). The estimated number of praziquantel doses needed per year was 1.99 million (95% CrI: 1.92-2.03 million) for the entire population in endemic areas of Southeast Asia., Conclusions: The burden of schistosomiasis remains far from the WHO goal and our estimates highlighted areas to target with strengthened interventions against schistosomiasis., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Vaccination is effective to prevent hepatitis B virus (HBV) infection. However, there is still a risk of infection after vaccination. In clinical work, we found that newborns were positive for HBV surface antigen (HBsAg) after vaccination., Objectives: To determine the effect of hepatitis B vaccination on the detection of HBsAg trend in newborns., Methods: We collected data at birth, history of vaccination for hepatitis B, quantitative HBsAg results, and other information about newborns born in our hospital from July 2017 to July 2020. Serum samples from healthy neonates were randomly selected to be supplemented with recombinant hepatitis B vaccine on a concentration gradient, and HBsAg was measured quantitatively., Results: Data from 1417 neonates were included in the study; 306 (21.6%) were HBsAg positive within 8 d after vaccination, with levels ranging from 0.104 IU/mL to 0.339 IU/mL. The proportion of neonates with HBsAg-positive serum was significantly correlated with the level of hepatitis B surface antibodies (anti-HBs) in the serum of their mothers ( P < 0.01). Experiments in vitro showed that the proportion of neonates with HBsAg-positive serum was correlated with the dose of the hepatitis B vaccine, and when the concentration of the hepatitis B vaccine reached 5 ng/mL and 10 ng/mL, the serum HBsAg levels showed a significant negative correlation with the original concentration of serum anti-HBs., Conclusions: Hepatitis B vaccination can affect the level of HBsAg detected in neonatal serum, and the effect could be mitigated by delaying the measurement. Moreover, maternal anti-HBs offset the effects of neonatal vaccination on HBsAg serum levels., (© 2022 Shuqi Wang et al., published by Sciendo.)

Background: Thiamine and riboflavin deficiencies exist to varying degrees worldwide, especially in developing countries. Evidence regarding the association between thiamine and riboflavin intake and gestational diabetes mellitus (GDM) is scarce., Objectives: We aimed to evaluate the association of thiamine and riboflavin intake during pregnancy, including dietary source and supplementation, with GDM risk in a prospective cohort study., Methods: We included 3036 pregnant women (923 in the first trimester and 2113 in the second trimester) from the Tongji Birth Cohort. A validated semi-quantitative food frequency questionnaire and a lifestyle questionnaire were used to assess thiamine and riboflavin intake from dietary source and supplementation, respectively. GDM was diagnosed using the 75 g 2-h oral glucose tolerance test at 24-28 weeks of gestation. A modified Poisson regression or logistic regression model was used to evaluate the association between thiamine and riboflavin intake and GDM risk., Results: Dietary intake of thiamine and riboflavin was at low levels during pregnancy. In the fully adjusted model, compared with participants in quartile 1 (Q1), those who had more total thiamine and riboflavin intake had a lower risk of GDM during the first trimester [thiamine: Q2: RR: 0.58 (95% CI: 0.34, 0.98); Q3: RR: 0.45 (95% CI: 0.24, 0.84); Q4: RR: 0.35 (95% CI: 0.17, 0.72), P for trend = 0.002; riboflavin: Q2: RR: 0.63 (95% CI: 0.37, 1.09); Q3: RR: 0.45 (95% CI: 0.24, 0.87); Q4: RR: 0.39 (95% CI: 0.19, 0.79), P for trend = 0.006]. This association was also observed during the second trimester. Similar results were observed for the association between thiamine and riboflavin supplement use but not dietary intake and GDM risk., Conclusions: Higher intake of thiamine and riboflavin during pregnancy is associated with a lower incidence of GDM. This trial was registered at http://www.chictr.org.cn as ChiCTR1800016908., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Efficient transport of nucleic acid therapeutics into targeted cells is the key step of genetic modulation in disease treatment. Nowadays, delivery systems strongly rely on cationic materials, but how to balance the trade-off between effectiveness and toxicity of these exogenous materials remains incredibly challenging. Here, we take inspiration from nucleic acid chemistry and introduce a new concept of amphiphilic nucleic acids (ANAs), as an all-in-one platform for cation-free nucleic acid delivery, by programmatically conjugating two different artifical nucleobases with sequence-independent activities. Specifically, the hydrophilic artificial nucleobases in ANAs act as both delivery vectors and therapeutic cargos for integrated benefits, while the hydrophobic nucleobases enable molecular self-assembly for improved stability and endosomal membrane oxidation for enhanced endosomal escape. By virtue of these merits, this platform is successfully used for short interference RNA (siRNA) delivery, which demonstrates a high siRNA loading capacity, rapid cellular uptake, and efficient endosomal escape, eliciting remarkable gene silencing and synergistic inhibitory effects on cancer cell proliferation and migration. This work is a case study in exploiting the basis of nucleic acid chemistry to afford new paradigms for advanced cancer theranostics.

Purpose: To investigate the safety and efficacy of a reverse puncture device (RPD) and specimen eversion of the rectum for resection in total laparoscopic proctectomy., Methods: In a prospective study from August 2019 to March 2021, 40 patients underwent a procedure with an RPD and specimen eversion of the rectum for total laparoscopic low rectal cancer resection, that is natural orifice specimen extraction surgery (NOSES), were included in the NOSES group. Forty patients in the control group underwent conventional laparoscopic radical resection for low rectal cancer and were included in the LAP group. Intraoperative- and postoperative-related indicators, recovery and inflammatory factors, quality of life (QOL) and mental health were compared., Results: All operations were successfully completed. Compared with the LAP group, the NOSES group showed better short-term outcomes, such as time to eating, postoperative pain, and especially postoperative incision-related complications. At the same time, postoperative inflammatory factor levels, psychological trauma, life-related anxiety and depression scores, and QOL were better in the NOSES group than in the LAP group., Conclusions: The application of an RPD and specimen eversion of the rectum for total laparoscopic low rectal cancer resection is a technically feasible and safe approach with a short-term curative effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Qian, Huang, Xu, Chen, Cao, Wang, Luo and Xia.)

Objective: To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA., Methods: The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot., Results: YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated., Conclusion: YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Can Luo et al.)

Polymyxin B (PB) is introduced into the clinic as the last-line therapy against carbapenem-resistant Klebsiella pneumoniae (CRKP). Unfortunately, increased resistance to PB in Klebsiella pneumoniae ( K. pneumoniae ) has threatened global health. Resistance of K. pneumoniae to PB was induced by passaging in serial concentrations of PB and determined by microbroth dilution method. Growth characteristics of induced strains including growth curve, reversibility of resistance, and biofilm formation (crystal violet staining method) were measured. This study employed TMT-labeled quantitative proteomics and LC-MS/MS metabolomics analysis to investigate the key biological processes associated with PB resistance in K. pneumoniae . A total of 315 differentially expressed proteins (DEPs) were identified, of which 133 were upregulated and 182 were downregulated in the PB-resistant K. pneumoniae . KEGG enrichment analysis revealed that the DEPs were mainly involved in ATP-binding cassette (ABC) transporters and cationic antimicrobial peptide (CAMP) resistance. Proteins related to central carbon metabolism were inhibited in the PB-resistant K. pneumoniae , but proteins mediating LPS modification were activated. Transcriptional levels of CAMP resistance-related proteins were significantly different between PB-susceptible and -resistant K. pneumoniae . PB treatment led to an increase in reactive oxygen species (ROS) levels of K. pneumoniae . Metabolomics data demonstrated that 23 metabolites were significantly upregulated in PB-resistant K. pneumoniae and 5 were downregulated. The differential metabolites were mainly lipids, including glycerophospholipids, sphingolipids, and fatty acids. Exposure to PB resulted in increased level of phospholipid transport gene mlaF in K. pneumoniae . Our study suggested that membrane remodeling and inhibited central carbon metabolism are conducive to the development of PB resistance in K. pneumoniae ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Tian, Luo, Wang, Li and Wang.)

We investigated the regulatory effects of hypoxia-inducible factor-1a (HIF-1α) on glycolysis metabolism in esophageal carcinoma (ESCA) cells. A series of bioinformatics databases and tools were used to investigate the expression and role of HIF-1α in ESCA. The expression of HIF-1a in ESCA tissues and adjacent tissues was validated by real-time PCR. Small interfering RNA (siRNA) was used to inhibit HIF-1α-related genes in human ESCA cells (Eca109 and KYSE150). Cell proliferation was detected by the CCK-8 assay. The expression of HIF-1α and glycolytic enzymes were investigated by real-time PCR and Western blot. HIF-1α is highly expressed in ESCA and is involved in many biological processes such as cell hypoxia reaction, glucose metabolic process. Further in vitro experiments showed that expression of HIF-1α in Eca109 and KYSE150 significantly increased under hypoxia compared with normoxia conditions. Also, the glucose uptake and lactate production under hypoxia were higher. The expression levels of hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1), glycolysis-related genes, were significantly increased under hypoxia. After siRNA knockdown of HIF-1a in Eca109 and KYSE150, the glucose uptake and lactate production, as well as cell proliferation were significantly decreased under hypoxia, and HK2 and PDK1 were significantly downregulated. HIF-1α promotes glycolysis of ESCA cells by upregulating the expression of HK2 and PDK1 under hypoxia.

Glomerular mesangial cell (GMC) proliferation is a histopathological alteration in human mesangioproliferative glomerulonephritis (MsPGN) or in animal models of MsPGN, e.g., the rat Thy-1 nephritis (Thy-1N) model. Although sublytic C5b-9 assembly on the GMC membrane can trigger cell proliferation, the mechanisms are still undefined. We found that sublytic C5b-9-induced rat GMC proliferation was driven by extracellular signal-regulated kinase 1/2 (ERK1/2), sry-related HMG-box 9 (SOX9), and Cyclin D1. Here, ERK1/2 phosphorylation was a result of the calcium influx-PKC-α-Raf-MEK1/2 axis activated by sublytic C5b-9, and Cyclin D1 gene transcription was enhanced by ERK1/2-dependent SOX9 binding to the Cyclin D1 promoter (-582 to -238 nt). In addition, ERK1/2 not only interacted with SOX9 in the cell nucleus to mediate its phosphorylation at serine residues 64 (a new site identified by mass spectrometry) and 181 (a known site), but also indirectly induced SOX9 acetylation by elevating the expression of general control non-repressed protein 5 (GCN5), which together resulted in Cyclin D1 synthesis and GMC proliferation. Moreover, our in vivo experiments confirmed that silencing these genes ameliorated the lesions of Thy-1N rats and reduced SOX9 phosphorylation, acetylation and Cyclin D1 expression. Furthermore, the renal tissue sections of MsPGN patients also showed higher phosphorylation or expression of ERK1/2, SOX9, and Cyclin D1. In summary, these findings suggest that sublytic C5b-9-induced GMC proliferation in rat Thy-1N requires SOX9 phosphorylation and acetylation via enhanced Cyclin D1 gene transcription, which may provide a new insight into human MsPGN pathogenesis.

Resveratrol has been found to improve ethanol-induced diabetes. Although pancreatic β-cell senescence-induced β-cell mass loss plays a critical role in the progression of diabetes, the exact mechanism by which resveratrol improves ethanol-triggered β-cell senescence and its role in ethanol-induced diabetes remains unknown. Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 2.4 g/kg·bw ethanol with or without 100 mg/kg·bw resveratrol for 22 weeks. Resveratrol decreased the ethanol-induced augmentation in senescence-associated β-galactosidase (SA-β-gal)-positive area and attenuated reduction in β-cell mass, which were based on elevated levels of SIRT1 and proliferation marker Ki67 and reduced levels of senescence-associated markers (p-p38MAPK and p16 INK4a ). Similarly, resveratrol rescued the reduction in NAD + /NADH ratio and SIRT1 and inhibited the upregulation of p-p38MAPK and p16 INK4a in ethanol-treated INS-1 cells. Furthermore, supplementation with NAD + inducer nicotinamide mononucleotide, SIRT1 activator SRT1720 or p38MAPK inhibitor SB203580 effectively reversed ethanol-induced β-cell senescence, while supplementation with SIRT1 inhibitor Ex527 or NAD + inhibitor FK866 abrogated resveratrol-mediated antisenescence effects in INS-1 cells. Together, our results indicate that resveratrol improves ethanol-triggered β-cell senescence and consequently recovers β-cell mass loss by inhibiting p38MAPK/p16 pathway through an NAD + /SIRT1 dependent pathway., 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 © 2020 Elsevier Inc. All rights reserved.)

Liver stiffness is an essential clinical biomarker for diagnosing liver fibrosis and cirrhosis. In current clinical practice, elastography techniques are standard non-invasive diagnosis tools to assess stiffness of liver, using either Ultrasound (US) or magnetic resonance imaging (MRI). However, the US elastography yields ≈ 10 % failure rate and degraded performance on obese patients, while the MR elastography is costlier and less available. Compared with US and MRI, the computerized tomography (CT) imaging has not been widely used in measuring liver stiffness. In this paper, we performed a pilot study to assess if volumetric variations of liver can be captured from paired inspiratory-expiratory chest (PIEC) CT scans. To enable the assessment, we propose a Hierarchical Intra-Patient Organ-specific (HIPO) registration pipeline to quantify the partial liver volumetric variations with lung pressure from a respiratory cycle. The PIEC protocol is employed since it naturally provides two paired CT scans with liver deformation from regulated respiratory motions. For the subjects whose registration results passed both an automatic quantitative quality assurance (QA) and another visual qualitative QA, 6.0% average volumetric variations of liver were measured, from inspiratory phase to expiratory phase. Future clinical validations will be required to validate the findings in this pilot study.

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D 3 [1,25(OH) 2 D 3 ] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH) 2 D 3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5-6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH) 2 D 3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH) 2 D 3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH) 2 D 3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH) 2 D 3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH) 2 D 3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH) 2 D 3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH) 2 D 3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway.

Cervical cancer is the third leading cause of female death in the world. Serum microRNAs (miRNAs) are currently considered to be valuable as noninvasive cancer biomarkers, but their role in the prognosis of cervical cancer has not been elucidated. We aimed to find serum miRNAs that can be used as prognostic factors for cervical cancer. A traumatic pathological biopsy is the only reliable method for determining the severity of cervical cancer currently. Thus, noninvasive diagnostic markers are needed. The serological expression of candidate miRNAs were measured in 90 participants, including 60 patients with cervical cancer and 50 patients with cervical intraepithelial neoplasia. Two patients with cervical cancer were excluded from the study because of lack of data. miRNAs were evaluated by quantitative reverse transcription polymerase chain reaction. miR-143/-4636 appeared specific for cervical cancer compared with cervical intraepithelial neoplasia (P < .001). The classification performance of validated miRNAs for cervical cancer [Area under the receiver operating characteristic curve (AUC) = 0.942] was better than that reached by squamous cell carcinoma antigen (SCC-Ag; AUC = 0.727). Poor-differentiation group has lower miR-143/-4636 levels in serum (P < .05). miR-4636 level was correlated gross tumor volume and the depth of invasion (P < .0001). In our study, we found a combination of miR-143 and miR-4636 that is independently and strongly associated with cervical cancer prognosis and can be used as a clinically prognostic factor., (© 2019 Wiley Periodicals, Inc.)

Competing Interests: The authors declare no conflict of interest.

Chronic low-dose (2-3 mg/kg/day) rotenone infusion produces clinical features and biological markers of Parkinson's disease (PD) in some rats. A significant proportion of rats, however, die of acute rotenone toxicity. Most studies have focused on chronic rotenone-infused rats. It has not been established if the animals that die of acute low-dose rotenone toxicity manifest clinical or pathological evidence of PD. In the present study, six rats that received continuous 3 mg/kg/day subcutaneous rotenone infusion, became moribund and were euthanized after five days were compared with ten vehicle infused animals sacrificed 14, 28 or 56 days after placebo infusion. All rotenone-infused rats had significant motor function decline beginning one day after the infusion and progressive worsening in the physical condition until they became severely akinetic, at which point they were euthanized. In the substantia nigra of rotenone-treated rats, four of six had reduced numbers of tyrosine hydroxylase-positive neurons and all six had increased nigral alpha-synuclein expression. Our observations show that even a short duration of low-dose subcutaneous rotenone infusion can induce clinical and pathological markers of PD in some rats. The pathophysiology of the enhanced susceptibility to PD in some animals remains to be established.

Objective: To explore the feasibility, safety, and cosmetic efficacy of endoscope-assisted thyroidectomy (EAT) by chest approach., Methods: Fifty-one patients with single benign thyroid nodule < or = 4.0 cm in diameter, and without history of neck surgery or irradiation, 8 males and 43 females, aged 33.9 (18-64), underwent endoscope-assisted thyroidectomy by chest approach: a skin incision with the length of 4 cm was made in the chest, an endoscope was inserted, and subtotal or total thyroidectomy with the technique similar to that in conventional surgery was performed with naked eyes., Results: Subtotal thyroidectomy was performed in 49 patients, and total excision of unilateral thyroid lobe plus isthmus lobectomy and contralateral partial lobectomy was performed on the other 2 patients. No patient was transferred to traditional surgery. Only one case showed palsy of recurrent nerve. Most patients expressed with the cosmetic results., Conclusion: EAT is a feasible and safe procedure with rather good cosmetic

Aim: To explore the effect of Ginkgo biloba extract (GbE) on the levels of caspase-3 and amyloid precursor protein (APP) in normal rats' hippocampus., Methods: Immunohistochemistry method was used for qualitative analysis of the expressions of caspase-3 and APP, and an image analysis method was used for the quantification of the levels of caspase-3 and APP after GbE was administered to rats of different ages for 14 d., Results: The mean absorbance of staining of caspase-3 and APP was markedly higher in GbE group than that in control groups. The expressions of caspase-3 and APP were intensified in the hippocampus of rats after GbE administration., Conclusion: GbE can raise the levels of caspase-3 and APP in the hippocampus of normal rats.

Background & Objective: Recent research had showed that tumor cell adhesion molecular CD44 and matrix metalloproteinases (MMP) were expressed strongly in many tumors, and was associated closely with invasion and metastasis of the tumors. Ki-67 was one of the proliferative markers, which indicated the growth rate of tumor cells. However, the relationship among these markers and the invasion, metastasis, and recurrence of osteosarcoma was unclear yet. In this research the authors studied the expression of standard-type CD44(CD44s), MMP-9, and Ki-67 in osteosarcoma, and their relation to the invasion, metastasis, and recurrence of the tumor., Methods: Immunohistochemistry staining(SP method) was used to detect CD44s, MMP-9, and Ki-67 in cases of osteosarcoma. Bone benign disease or normal connective tissue were used as the control. The results were treated with semi-quantitative method and analyzed by using non-parameter rank sum test., Results: The positive rates of CD44s, MMP-9, and Ki-67 in osteosarcoma were 71.0%, 75.8%, and 35.5%, respectively, which were significantly higher than that in control tissue. The positive rate of Ki-67 in recurrent osteosarcoma was 81.8%, which was significantly higher than that in primary tumor. CD44s and Ki-67 positive rates were 88.9% and 66.7% respectively in osteosarcoma with lung metastasis, which were both significantly higher than that in osteosarcoma without lung metastasis. In poorly differentiated osteosarcoma positive rates of CD44s and MMP-9 were 76.3% and 79.7%, respectively, which were significantly higher than that in well differentiated tumor. Spearman correlation analysis proved that the expression of CD44s, MMP-9, and Ki-67 had significant relation to another., Conclusions: Increase of CD44s, MMP-9, and Ki-67 were involved in the growth and local invasion of osteosarcoma. The recurrence of osteosarcoma was associated with the proliferative rate of tumor cells. Whether there were early lung metastasis or not was affected by the amount of CD44s and the proliferative rate of the tumor cell. The poorer differentiation of osteosarcoma cells, the higher level of CD44s and MMP-9.

Experiments were performed in male Sprague-Dawley rats (150-200 g). A silver clip (0.2 mm internal diameter) was placed on the left renal artery of rats. After operation the rats were divided into 4 groups sham group, 2K1C (two-kidney one clip) group, 2K1C+Arg (2K1C and L-Arg 150 mg/kg x d(-1) by drinking) group, and 2K1C+NAME (2K1C and L-NAME 10 mg/kg x d(-1) i.p.) group. The animals were studied at two time points (4 and 7 weeks after operation) corresponding to phases I and II of Goldblatt hypertension. The animals were deeply anesthetized with pentobarbital and perfused by the cardiac route with saline (100 ml) and freshly prepared 4% paraformaldehyde in phosphate buffer (300 ml). The caudal medulla was removed, then placed in 25% sucrose in PB for 12 h in a 4 degrees C fridge. The 40 microm coronal slices of brainstems were cut with cryostat, collected in PBS for nNOS study by immunohistochemistry. The results showed that (1) only a few neuronal nitric oxide synthase (nNOS) positive neurones were found in caudal medulla, including the depressor area of the ventral surface of medulla oblongata (VSMd) and the caudal pressor area (CPA) of the sham operated animals. The number of nNOS positive neurons in caudal medulla was significantly increased in 2K1C Goldblatt hypertension rats at 4 and 7 weeks. (2) The number of nNOS positive neurons in VSMd and CPA were 2K1C+Arg > 2K1C >2K1C +NAME > sham. (3) L-Arg enhanced the expression of nNOS whereas L-NAME inhibited the expression of nNOS in caudal medulla. (4) The character of nNOS expression was similar in Goldblatt hypertension rats at 4 weeks with that of the rats at 7 weeks.