The meso-substituent electronic effect of Fe porphyrins on the electrocatalytic CO2 reduction reaction.

We report Fe porphyrins bearing different meso-substituents for the electrocatalytic CO2 reduction reaction (CO2RR). By replacing two and four meso-phenyl groups of Fe tetraphenylporphyrin (FeTPP) with strong electron-withdrawing pentafluorophenyl groups, we synthesized FeF10TPP and FeF20TPP, respectively. We showed that FeTPP and FeF10TPP are active and selective for CO2-to-CO conversion in dimethylformamide with the former being more active, but FeF20TPP catalyzes hydrogen evolution rather than the CO2RR under the same conditions. Experimental and theoretical studies revealed that with more electron-withdrawing meso-substituents, the Fe center becomes electron-deficient and it becomes difficult for it to bind a CO2 molecule in its formal Fe0 state. This work is significant to illustrate the electronic effects of catalysts on binding and activating CO2 molecules and provide fundamental knowledge for the design of new CO2RR catalysts.

Mechanistic Studies of Stimulus-Response Integrated Catalysis of Single-Atom Alloys under Electric Fields for Electrochemical Nitrogen Reduction.

The present work introduces a novel catalytic strategy to promote the nitrogen reduction reaction (NRR) by employing a cooperative Cu-based single-atom alloy (SAA) and oriented external electric fields (OEEFs) as catalysts. The field strength (F)-dependent reaction pathways are investigated by means of first-principles calculations. Different dipole-induced responses of intermediates to electric fields break the original scaling relationships and effectively tune not only the activity but also the product selectivity of the NRR. When the most active Os1Cu SAA is taken as an example, in the absence of an OEEF, the overpotential (η) of the NRR is 0.62 V, which is even larger than that of the competitive hydrogen evolution reaction (HER). A negative field not only reduces η but switches the preference to the NRR over the HER. In particular, η at F = -1.14 V/Šreaches the bottom of 0.18 V, which is 70% lower than that in the field-free state.

Sensorimotor delays constrain robust locomotion in a 3D kinematic model of fly walking.

Walking animals must maintain stability in the presence of external perturbations, despite significant temporal delays in neural signaling and muscle actuation. Here, we develop a 3D kinematic model with a layered control architecture to investigate how sensorimotor delays constrain robustness of walking behavior in the fruit fly, Drosophila. Motivated by the anatomical architecture of insect locomotor control circuits, our model consists of three component layers: a neural network that generates realistic 3D joint kinematics for each leg, an optimal controller that executes the joint kinematics while accounting for delays, and an inter-leg coordinator. The model generates realistic simulated walking that matches real fly walking kinematics and sustains walking even when subjected to unexpected perturbations, generalizing beyond its training data. However, we found that the model's robustness to perturbations deteriorates when sensorimotor delay parameters exceed the physiological range. These results suggest that fly sensorimotor control circuits operate close to the temporal limit at which they can detect and respond to external perturbations. More broadly, we show how a modular, layered model architecture can be used to investigate physiological constraints on animal behavior.

Regulation of PDGFRα+ cells and ICC in progesterone-mediated slow colon transit in pregnant mice.

Background: Progesterone can inhibit intestinal smooth muscle contraction; however, the specific mechanism remains unclear. Besides smooth muscle cells, smooth muscle has two important mesenchymal cells, namely interstitial cells of Cajal (ICC) and PDGFRα+ cells, which induce the contraction and relaxation of smooth muscles. We aimed to explore the regulation of PDGFRα+ cells and ICC in progesterone-mediated colon slow transit in pregnant mice. Methods: Colon transit experiments were performed in vivo and in vitro to observe slow colon transit. The expression of PDGFRα and c-KIT was detected by Western blot, RT-PCR, and immunofluorescence. An isometric tension experiment was performed to investigate smooth muscle contractions. Results: The colon transit time in pregnant mice was longer than that in non-pregnant mice. Progesterone significantly blocks colonic smooth muscle contractions. However, when the relaxation and contraction of PDGFRα+ cells and ICC are blocked, progesterone cannot inhibit smooth muscle contraction. When the function of only PDGFRα+ cells are blocked, progesterone has a more obvious inhibitory effect on smooth muscle in the non-pregnant group than that in the pregnant group. However, when ICC alone was blocked, progesterone inhibited smooth muscle contractions more clearly in pregnant mice. The protein and mRNA expression of PDGFRα was higher and c-KIT was lower in pregnant mice. PDGFRα+ cells and ICC from smooth muscle all co-localize progesterone receptors. Conclusions: Under the regulation of progesterone, the relaxation function of PDGFRα+ cells is enhanced and the contraction function of ICC is weakened, leading to the slow colon transit of pregnant mice.

LINC00958 promotes the malignant biological behaviors of cervical cancer cells and lymph node metastasis in mouse models by upregulating VEGF-C expression / 中国肿瘤生物治疗杂志

@#目的：探讨LINC00958/血管内皮生长因子C（VEGF-C）信号通路在宫颈癌的淋巴管生成和淋巴转移中的作用。方法：从2020年9月至2022年9月期间在河南省人民医院接受手术的患者中收集了42例宫颈癌组织标本，通过qPCR检测宫颈癌组织和宫颈癌细胞（Hela、C33A、SiHa、Caski）中LINC00958的表达情况。将LINC00958过表达载体（LINC00958组）或对照载体（CMV组）转染Caski细胞，敲减LINC00958（shLINC00958组）、VEGF-C（shVEGF-C组）的shRNA序列或阴性对照shRNA（shNC组）转染SiHa细胞。分别通过CCK-8法、Transwell实验检测过表达或敲减LINC00958对宫颈癌细胞增殖、迁移和侵袭的影响。观察转染后细胞的培养上清液对人淋巴管内皮细胞（HLEC）淋巴管形成能力的影响。建立小鼠腘淋巴结转移模型，观察过表达LINC00958或同时敲减VEGF-C对宫颈癌淋巴结转移的影响。结果：LINC00958在宫颈癌组织中呈高表达（P<0.001），高水平的LINC00958与大肿瘤、晚期肿瘤分级、浸润深度和淋巴转移有关联（P<0.05或P<0.01）。与正常人宫颈上皮细胞ende1617相比，宫颈癌细胞中LINC00958水平均显著升高（P<0.01或P<0.001）。shLINC00958组SiHa细胞的增殖、迁移、侵袭能力及其培养上清液的促HLEC淋巴管形成能力均显著低于shNC组（P<0.05、P<0.01或P<0.001），LINC00958组Caski细胞的增殖、迁移、侵袭能力及其培养上清液的促HLEC淋巴管形成能力显著高于CMV组（P<0.05、P<0.01或P<0.001）。通过RNA下拉、RNA免疫沉淀实验发现宫颈癌细胞中LINC00958能够特异性结合VEGF-C。LINC00958+shVEGF-C组Caski细胞的增殖、迁移、侵袭能力及其培养上清液的促淋巴管形成能力显著低于LINC00958组（P<0.01或P<0.001）；在小鼠腘淋巴结转移模型中，LINC00958+shVEGF-C组中小鼠腘窝淋巴结的体积和VEGF-C蛋白、N-cadherin蛋白以及LYVE-1的阳性细胞比例均显著低于LINC00958组（均P<0.001）。结论：LINC00958通过直接与VEGF-C蛋白相互作用增强宫颈癌细胞的增殖、侵袭、淋巴管生成能力，促进小鼠腘淋巴结转移模型的淋巴结转移。

Development and validation of a scoring system to predict esophagogastroduodenoscopy necessity.

OBJECTIVE: This study aimed to develop and validate a scoring system for predicting the need for esophagogastroduodenoscopy (EGD) in clinical practice to enhance accuracy and reduce misapplications. METHODS: From February 2021 to April 2022, outpatients scheduled for EGD at the Department of Gastroenterology in our hospital were recruited. Patients completed the system evaluation by providing clinical symptoms, relevant medical history, and endoscopic findings. Patients were randomly divided into the training and validation cohorts (at 2:1 ratio). The optimal algorithm was selected from five alternatives including a parallel test. Six physicians participated in a human-computer comparative validation. Sensitivity and negative likelihood ratio (-LR) were used as the primary indicators. RESULTS: Altogether 865 patients were enrolled, with 578 in the training cohort and 287 in the validation cohort. The scoring system comprised 21 variables, including age, 13 typical clinical symptoms, and seven medical history variables. The parallel test was selected as the final algorithm. Positive EGD findings were reported in 54.5% of the training cohort and 62.7% of the validation cohort. The scoring system demonstrated a sensitivity of 79.0% in the training cohort and 83.9% in the validation cohort, with -LR being 0.627 and 0.615, respectively. Compared to physicians, the scoring system exhibited higher sensitivity (84.0% vs 68.7%, P = 0.02) and a lower -LR (1.11 vs 2.41, P = 0.439). CONCLUSIONS: We developed a scoring system to predict the necessity of EGD using a parallel test algorithm, which was user-friendly and effective, as evidenced by single-center validation.

Construction of Naphthalene Diimide Derived Nanostructured Cathodes through Self-Assembly for High-Performance Sodium-Organic Batteries.

Organic nanostructured electrodes are very attractive for next-generation sodium-ion batteries. Their great advantages in improved electron and ion transport and more exposed redox-active sites would lead to a higher actual capacity and enhanced rate performance. However, facile and cost-effective methods for the fabrication of nanostructured organic electrodes are still highly challenging and very rare. In this work, we utilize a bioinspired self-assembly strategy to fabricate nanostructured cathodes based on a rationally designed N-hydroxy naphthalene imide sodium salt (NDI-ONa) for high-performance sodium-organic batteries. Such a well-organized nanostructure can greatly enhance both ion and electron transport. When used as cathode for sodium-organic batteries, it provides among the best battery performances, such as high capacity (171 mA h g-1 at 0.05 A g-1), excellent rate performance (153 mA h g-1 at 5.0 A g-1), and ultralong cycling life (93% capacity retention after 20000 cycles at 3.0 A g-1). Even at low temperature or without a conductive additive, it can also perform well. It is believed that self-assembly is a very powerful strategy to construct high-performance nanostructured electrodes.

Internal feedback in the cortical perception-action loop enables fast and accurate behavior.

Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.

The effect of luteinizing hormone changes in GnRH antagonist protocol on the outcome of controlled ovarian hyperstimulation and embryo transfer.

BACKGROUD: To investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. METHODS: A total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2). RESULTS: There were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001). CONCLUSION: LH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.

Development of tetracycline-modified nanoparticles for bone-targeted delivery of anti-tubercular drug.

Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs). Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice. Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8 nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60 h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC-PLGA-PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094 µg/mL, whereas this of free rifapentine was 0.25 µg/mL. Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.

Effect of Momordica charantia polysaccharide on immunomodulatory activity in mice.

Momordica charantia polysaccharides (MCPs) have been reported to exert beneficial roles, such as disease healing, in medicine and pharmacy. However, little is known about their effects on immunomodulation. The present study aimed to explore the possible effects of Momordica charantia polysaccharide (MCP) on the immunomodulatory activity of mice lymphocytes. To this aim, male BALB/c mice aged 6-8 weeks were assigned to the following six experimental groups: i) Normal (NG); ii) model (MG); iii) positive (PG); iv) MCP low-dose (MLG); v) MCP medium-dose (MMG); and vi) MCP high-dose (MHG). An immunosuppressive model was established by the intraperitoneal injection of cyclophosphamide in all groups apart from NG. The NG and MG mice were fed with distilled water, whereas the PG mice were administered with levamisole and the MLG, MMG and MHG mice were fed on low, medium and high (100, 200 and 300 mg/kg, respectively) doses of MCP for 21 consecutive days. Subsequently, the mice underwent surgical procedure and were analysed using a range of procedures, including measurement of the thymus index (TI) and spleen index (SI), assessment of the lymphocyte proliferation rate and cell phagocytosis of peritoneal macrophages, lymphocyte proliferation, secretion and mRNA expression of cytokines IFN-γ, IL-6 and IL-12. The mice divided into six groups as mentioned above and treated for 7 days, in the first 6 days, except NG group, mice in each group were desiccated in the abdominal cavity and sensitized by 1% dinitrofluorobenzene (DNFB). On day 6, mice were sensitized with 20 µl DNFB/acetone/olive oil solution behind the right ear and in front of the right ear. Compared with those in the NG mice (not injected with 80 mg/kg cyclophosphamide), the TIs and SIs of the PG, MLG, MMG and MHG mice were increased. In addition, the inhibitory rate of ear swelling and the phagocytic activity of peritoneal macrophages in the PG, MLG, MMG and MHG mice were increased compared with those of MG. Furthermore, the lymphocyte proliferation rate, the secretion and relative mRNA expression levels of cytokines IFN-γ, IL-6 and IL-12 were significantly increased in the PG, MMG and MHG mice compared with those in the NG mice. The results from the present study suggest that treatment with MCP led to an upregulation of the organ indices of immunosuppressed mice, reduced their delayed allergic reaction indicated by the differential cytokine levels, improved the phagocytic activity of peritoneal macrophages, enhanced the proliferation rate of lymphocytes, increased the secretion and expression of IFN-γ, IL-6 and IL-12. Therefore, MCP may improve the immune function of the immunosuppressed mice.

In Situ Construction of Heterostructured Co3O4/CoP Nanoflake Arrays on Carbon Cloth as Binder-Free Anode for High-Performance Lithium-Ion Batteries.

Cobalt oxide (Co3O4) is regarded as the anode material for lithium-ion batteries (LIBs) with great research value owing to its environmental friendliness and exceptional theoretical capacity. However, the low intrinsic conductivity, poor electrochemical kinetics, and unsatisfactory cycling performance severely limit its practical applications in LIBs. The construction of a self-standing electrode with heterostructure by introducing a highly conductive cobalt-based compound is an effective strategy to solve the above issues. Herein, Co3O4/CoP nanoflake arrays (NFAs) with heterostructure are constructed skillfully directly grown on carbon cloth (CC) by in situ phosphorization as an anode for LIBs. Density functional theory simulation results demonstrate that the construction of heterostructure greatly increases the electronic conductivity and Li ion adsorption energy. The Co3O4/CoP NFAs/CC exhibited an extraordinary capacity (1490.7 mA h g-l at 0.1 A g-l) and excellent performance at high current density (769.1 mA h g-l at 2.0 A g-l), as well as remarkable cyclic stability (451.3 mA h g-l after 300 cycles with a 58.7% capacity retention rate). The reasonable construction of heterostructure can promote the interfacial ion transport, significantly enhance the adsorption energy of lithium ions, improve the conductivity of Co3O4 electrode material, promote the partial charge transfer throughout the charge and discharge cycles, and enhance the overall electrochemical performance of the material.

[Analysis of Microbial Community Characteristics and Function Prediction of MBBR with Magnetic Biocarriers at Low Temperature].

In order to clarify effect of magnetic biocarriers on the performance of MBBR at low temperatures, the microbial diversity, community structure, functional characteristics, and nitrogen metabolism of biofilm in the reaction system were investigated. The results indicated that MBBR with magnetic biocarriers had a better pollutant removal efficiency, with the average removal rates of NH4+-N and TN being 16.2% and 12.1% higher than those in the control group (commercial biocarriers), respectively. Illumina high-throughput sequencing analysis showed that higher diversity and richness of the bacterial community was established in the biofilm of magnetic biocarriers. There were obvious differences in microbial community structure of biofilm between the two biocarrier duos to bacterial magnetic susceptibility. The relative abundances of nitrifying bacteria (e.g., Nitrosomonas and Nitrospira) and denitrifying bacteria (e.g., Sphaerotilus and Zoogloea) were increased in the magnetic biocarriers. Functional prediction analysis with PICRUSt2 showed that the microorganism of magnetic biocarriers had a better total gene function expression level, which was significantly more increased than commercial biocarriers in gene-representing signal transduction mechanisms and intracellular trafficking, secretion, and vesicular transport. Furthermore, most of the abundances of nitrogen metabolism genes were raised in the biofilm of magnetic biocarriers (e.g., genes amo and hao, were responsible for nitrification, and genes nap and nor, which were responsible for denitrification). Magnetic biocarriers increased biofilm potential for denitrification at low temperatures. Our results explained the difference in performance between the two reactors from microbiology and provided the theoretical basis for magnetic biocarrier-enhanced performances of MBBR at low temperatures.

Rabies Virus Neutralizing Activity, Safety, and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults.

Objective: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. Methods: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. Results: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. Conclusion: The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.

Defective hBN-Supported Fe2N Single Cluster Catalyst for Active and Selective Electro-Reduction of Multiple CO to Propane: Theoretical Elucidation of Metal-Nonmetal Synergic Effects.

The present work introduces the multiple CO reduction toward C3 products promoted by a newly designed single cluster catalyst consisting of defective hBN and embedded dimerized Fe, by means of density functional theory calculations. We find the strong metal-support interactions give rise to the local strain and electron accumulation of the N coordinated with two metals and resultantly form a Fe2N active center. The metal-nonmetal synergic effect facilitates the coadsorption and C-C coupling of triple CO molecules and finally generates propane in a highly active and selective way.

Nitrogen Electroreduction on Borophene-Supported Atomic and Diatomic Transition Metals: Stability, Activity and Selectivity Improvements via Defect-Engineering.

The present work investigated the binding of atomically dispersed transition metals to the perfect and single/double vacancy (SV/DV)-containing defective ß12 -borophenes and the catalytic performance of those corresponding single-atom catalysts (SACs) and diatomic catalysts (DACs) for nitrogen reduction reaction (NRR) by means of density functional theory calculations. Although previous theoretical studies proposed that the inherent hexagon hole of the defect-free ß12 -borophene is capable of anchoring single metal atom for NRR, calculations suggested that the interaction between borophene and doped metal is not strong enough to avoid metal aggregation. For the defective ß12 -borophene with SV, even though the single metal could be stabilized in an 8-membered ring, it was found that the SAC was still ineffective for NRR because of the competitive hydrogen evolution process. Regarding the DV-containing ß12 -borophene, a defective configuration with an unexpected 11-membered hole was proved as the most stable structure, which possessed a very similar average atomic energy (6.25 eV atom-1 ) compared to that of the pristine ß12 sheet (6.26 eV atom-1 ). Two metal atoms could be encapsulated into the confined space of the B11 ring. Compared to SACs, those corresponding DACs were more active for N2 fixation and hydrogenation, and the hydrogen evolution reaction could be passivated, attributing to the synergistic effect of dual metal centres. Among all candidates, the V2 /ß12 -DV was predicted as the most promising catalyst for NRR, with the limiting potential of as low as -0.15 V.

[Effect mechanism of blistering moxibustion on visceral hypersensitivity of irritable bowel syndrome in mice based on 5-HT signal pathway].

OBJECTIVE: To observe the effect of blistering moxibustion on the expression levels of 5-hydroxytyptamine (5-HT) and its receptors of the colon tissue in the mice with visceral hypersensitivity of irritable bowel syndrome (IBS), so as to explore the effect mechanism of blistering moxibustion in treatment of IBS. METHODS: Forty SPF-grade newborn Kunming mice were randomly divided into a normal group, a model group, an antagonist group and a blistering moxibustion group, 10 mice in each one. Before modeling, the injection with 0.2 mL parachlorophenylalanine (PCPA) was given on the lateral ventricle in the antagonist group. The endorectal glacial acetic acid stimulation combined with tail clipping was used to prepare the model of visceral hypersensitivity of IBS in the model group, the antagonist group and the blistering moxibustion group. After modeling, in the blistering moxibustion group, the intervention with blistering moxibustion was exerted at "Zhongwan" (CV 12), "Tianshu" (ST 25) and "Zusanli" (ST 36), once herbal irritant plaster at each acupoint, for 2 h each time, once a week, consecutively for 3 weeks. Abdominal withdrawal reflex (AWR) score and electromyographic (EMG) amplitude of abdominal muscles were adopted to evaluate the visceral hypersensitivity. HE staining was applied to observe the morphological changes in colon tissue, and immunohistochemistry was to determine the expression levels of 5-HT and its receptors. RESULTS: Compared with the normal group, EMG amplitude of abdominal muscles was increased under 20, 40 mm Hg (1 mm Hg=0.133 kPa) in the model group (P<0.05), AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all increased in the model group (P<0.05). In comparison with the model group, EMG amplitude of abdominal muscles was reduced under 20 mm Hg in the blistering moxibustion group (P<0.05), AWR scores were increased under 40 mm Hg in both the blistering moxibustion group and the antagonist group (P<0.05); AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all reduced in both the blistering moxibustion group and the antagonist group (P<0.05). Compared with the normal group, in the model group, the mucosa was slightly disturbed, while, the moderate inflammatory cells were visible in the submucosa. In comparison with the model group, the inherent glands of mucosa were regular in shape and a small number of inflammatory cells were visible in both the blistering moxibustion group and the antagonist group. In comparison with the normal group, the average positive staining area percentage (APSAP) of 5-HT and 5-HT3R of the colon tissue was increased, while, APSAP of 5-HT4R was reduced in the model group (P<0.05). Compared with the model group, APSAP of 5-HT and 5-HT3R was reduced in both the blistering moxibustion group and the antagonist group (P<0.05). CONCLUSION: Blistering moxibustion can relieve the visceral hypersensitivity of the mice with visceral hypersensitive IBS and the underlying mechanism is related to the regulation of the gut-brain axis mediated by 5-HT signaling pathway.

Efficacy of ormutivimab, a novel recombinant human anti-rabies monoclonal antibody, in post-exposure prophylaxis animal models.

Human rabies is a serious public health problem that can't be ignored. Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP). However, current PEP relies on RIG purified from pooled human or equine plasma, which are either in chronic shortage or associated with safety concerns. Monoclonal antibodies have become widely accepted as safer and more cost-effective alternatives to RIG products in recent years. Here, we assessed the neutralization breadth of human monoclonal antibody ormutivimab and its protective efficacy in PEP models. Ormutivimab was able to neutralize a broad panel of Chinese prevalent street RABVs with neutralizing potency form 198-1487.6 IU/mL. Furthermore, ormutivimab offered comparable protection to that with HRIG both at standard doses (20 IU/kg) and higher doses (100 IU/kg and 200 IU/kg). The interference of ormutivimab on vaccine potency was also analyzed and found slightly reduced neutralizing antibody titers similar to HRIG. The broad-spectrum neutralization activities, highly protective potency, and rapid onset of action make ormutivimab an effective candidate for human rabies PEP.

Dense hyperthermic intraperitoneal chemotherapy with cisplatin in patients with stage III serous epithelial ovarian cancer: a retrospective study.

BACKGROUND: To investigate the efficacy and safety of interval debulking surgery (IDS) combined with dense hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in Chinese patients with FIGO stage III serous epithelial ovarian cancer (EOC). METHODS: This retrospective single-center study reviewed the demographic and clinical data of 197 patients with primary FIGO stage III serous EOC who were treated with IDS with (n = 121) or without (n = 76, control group) dense HIPEC between January 2012 and April 2017. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was the occurrence of adverse events. RESULTS: The median PFS was 24 months in the IDS plus dense HIPEC group, whereas it was 19 months in the IDS alone group (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.33-0.65, p = 0.000). The median OS in patients treated with IDS plus dense HIPEC (51 months) was significantly longer than that in patients treated with IDS alone (40 months, HR 0.52, 95% CI: 0.35-0.78, p = 0.001). The demographic and preoperative clinical characteristics of these two groups were comparable (p > 0.05). In the IDS alone group, no adverse events were recorded in 42 (55.3%) of the 76 patients, and 14 (18.4%) patients were reported to have grade III/IV adverse events. In the IDS plus dense HIPEC group, no adverse events were recorded in 55 (45.5%) of the 121 patients, and 23 (19.0%) patients were reported to have grade III/IV adverse events. No postoperative deaths occurred within 30 days in either group and neither did severe fatal complications in the IDS plus dense HIPEC group. CONCLUSIONS: IDS plus dense HIPEC with cisplatin in Chinese patients with FIGO stage III serous EOC is associated with improved survival and is reasonably well tolerated by patients.

Global dynamics of a delayed alcoholism model with the effect of health education.

An alcohol consumption model with health education and three time delays is formulated and analyzed. The alcoholism generation number is defined. Two steady states of the model are found. At the same time, the corresponding global dynamics of the model are analyzed respectively in four cases with different time delays. Then, the effects of health education and three time delays in controlling the alcohol problem are discussed. Some numerical simulation results are also given to support our theoretical predictions.