Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction.

This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.

Triple-junction solar cells with cyanate in ultrawide-bandgap perovskites.

Perovskite bandgap tuning without quality loss makes perovskites unique among solar absorbers, offering promising avenues for tandem solar cells1,2. However, minimizing the voltage loss when their bandgap is increased to above 1.90 eV for triple-junction tandem use is challenging3-5. Here we present a previously unknown pseudohalide, cyanate (OCN-), with a comparable effective ionic radius (1.97 Å) to bromide (1.95 Å) as a bromide substitute. Electron microscopy and X-ray scattering confirm OCN incorporation into the perovskite lattice. This contributes to notable lattice distortion, ranging from 90.5° to 96.6°, a uniform iodide-bromide distribution and consistent microstrain. Owing to these effects, OCN-based perovskite exhibits enhanced defect formation energy and substantially decreased non-radiative recombination. We achieved an inverted perovskite (1.93 eV) single-junction device with an open-circuit voltage (VOC) of 1.422 V, a VOC × FF (fill factor) product exceeding 80% of the Shockley-Queisser limit and stable performance under maximum power point tracking, culminating in a 27.62% efficiency (27.10% certified efficiency) perovskite-perovskite-silicon triple-junction solar cell with 1 cm2 aperture area.

NR5A2 promotes malignancy progression and mediates the effect of cisplatin in cutaneous squamous cell carcinoma.

INTRODUCTION: Nuclear receptor subfamily five group A member two (NR5A2) plays a key role in the development of many tumor types, while it is uncertain in cutaneous squamous cell carcinoma (cSCC). The aim of this work was to determine the role of NR5A2 in cSCC proliferation, and to determine whether NR5A2 mediates the effect of cisplatin in cSCC. METHODS: We performed a systematic study of existing data and conducted a preliminary bioinformatics analysis of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining was performed on cSCC tissues of seven patients to study NR5A2 expression. NR5A2 expression was examined in human keratin-forming cells (HaCaT) and human cSCC cells (A431, Colo-16, SCL-1, SCL-2, and HSC-5). Stable A431 and SCL-2 cell lines consisting of sh-RNA-NR5A2 were constructed to detect changes in cell proliferation, cell cycle, apoptosis, and to determine the key proteins in the Wnt/ß-catenin pathway. We also investigated changes in the effects of cisplatin on cSCC cells by CCK-8, clone formation assay, and Flow apoptosis assay after NR5A2 knockdown. RESULTS: NR5A2 showed enhanced expression in cSCC tissues than in healthy tissues. Downregulation of NR5A2 in cSCC cells led to the formation of a less malignant phenotype. In contrast, the proliferative capacity of the cSCC cells was enhanced posttreatment with RJW100, an NR5A2 agonist. Additionally, NR5A2 knockdown led to a decrease in the expression level of the proteins in the Wnt/ß-catenin pathway, and this inhibition was reversed by LiCl and recombinant antibody, Wnt3a. Moreover, NR5A2 knockdown resulted in diminished proliferative capacity and increased apoptotic cells after the addition of cisplatin. CONCLUSION: NR5A2 plays a crucial role in the progression of cSCC, and the Wnt/ß-catenin signaling pathway may be involved in the regulation of NR5A2-mediated cSCC. Knockdown of NR5A2 enhanced both the proliferation inhibiting and apoptosis promoting effects of cisplatin on cSCC.

Constructing tin oxides Interfacial Layer with Gradient Compositions for Efficient Perovskite/Silicon Tandem Solar Cells with Efficiency Exceeding 28.

Atomic layer deposition (ALD) growth of conformal thin SnOx films on perovskite absorbers offers a promising method to improve carrier-selective contacts, enable sputter processing, and prevent humidity ingress toward high-performance tandem perovskite solar cells. However, the interaction between perovskite materials and reactive ALD precursor limits the process parameters of ALD-SnOx film and requires an additional fullerene layer. Here, it demonstrates that reducing the water dose to deposit SnOx can reduce the degradation effect upon the perovskite underlayer while increasing the water dose to promote the oxidization can improve the electrical properties. Accordingly, a SnOx buffer layer with a gradient composition structure is designed, in which the compositionally varying are achieved by gradually increasing the oxygen source during the vapor deposition from the bottom to the top layer. In addition, the gradient SnOx structure with favorable energy funnels significantly enhances carrier extraction, further minimizing its dependence on the fullerene layer. Its broad applicability for different perovskite compositions and various textured morphology is demonstrated. Notably, the design boosts the efficiencies of perovskite/silicon tandem cells (1.0 cm2) on industrially textured Czochralski (CZ) silicon to a certified efficiency of 28.0%.

Guilingji capsule for Alzheimer's disease: secondary analysis of a randomized non-inferiority controlled trial.

OBJECTIVE: To investigate the effectiveness and safety of Guilingji capsule (, GLJC) in treatment of Alzheimer's disease (AD) patients with kidney-marrow deficiency pattern (KMDP) compared with gingko extract tablets. METHODS: This is a secondary analysis of a large-scale multicenter randomized non-inferiority clinical trial. A total of 120 AD patients with KMDP were enrolled in this study. The participants were randomly categorized into two groups: (a) GLJC group ( = 60) and (b) gingko group ( = 60). The GLJC group was treated with GLJC and gingko extract mimetic tablets, whereas the gingko group received gingko extract tablets and mimetic GLJC. The data on the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Activities of Daily Living (ADL), and Chinese Medicine Symptom Scale (CM-SS) was evaluated at 0, 12, and 24 weeks of treatment. The serum levels of acetylcholine (Ach), acetylcholinesterase (AchE), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the participants were measured before and after 24 weeks of treatment. The safety was based on the incidence of adverse events. RESULTS: Both interventions significantly increased the MMSE scores of the participants and decreased their ADAS-Cog, ADL, and CM-SS scores ( < 0.01). Compared with the gingko group, the GLJC group had a higher effective rate of improvement in the symptoms of "amnesia" and "dull expression and slow thinking" at the 12th week and 24th week ( < 0.05, < 0.01). In the GLJC group, serum Bcl-2 levels were significantly increased at the 24th week ( < 0.05). Serum Bax and AchE levels of the two groups were significantly decreased at the 24th week ( < 0.01). No treatment-related adverse events were reported in the two groups. CONCLUSIONS: GLJC is equivalent to the gingko extract tablets in terms of improving cognitive function and the quality of life in AD patients with KMDP and has good clinical efficacy and safety. When it comes to improving TCM symptoms and anti-aging, GLJC is even more advantageous.

Buried-Interface Engineering of Conformal 2D/3D Perovskite Heterojunction for Efficient Perovskite/Silicon Tandem Solar Cells on Industrially Textured Silicon.

Exploring strategies to control the crystallization and modulate interfacial properties for high-quality perovskite film on industry-relevant textured crystalline silicon solar cells is highly valued in the perovskite/silicon tandem photovoltaics community. The formation of a 2D/3D perovskite heterojunction is widely employed to passivate defects and suppress ion migration in the film surface of perovskite solar cells. However, realizing solution-processed heterostructures at the buried interface faces solvent incompatibilities with the challenge of underlying-layer disruption, and texture incompatibilities with the challenge of uneven coverage. Here, a hybrid two-step deposition method is used to prepare robust 2D perovskites with cross-linkable ligands underneath the 3D perovskite. This structurally coherent interlayer benefits by way of preferred crystal growth of strain-free and uniform upper perovskite, inhibits interfacial defect-induced instability and recombination, and promotes charge-carrier extraction with ideal energy-level alignment. The broad applicability of the bottom-contact heterostructure for different textured substrates with conformal coverage and various precursor solutions with intact properties free of erosion are demonstrated. With this buried interface engineering strategy, the resulting perovskite/silicon tandem cells, based on industrially textured Czochralski (CZ) silicon, achieve a certified efficiency of 28.4% (1.0 cm2 ), while retaining 89% of the initial PCE after over 1000 h operation.

Evaluation and comparison of physicochemical properties, volatile substances, and microbial communities of leaf mustard (Brassica juncea var. multiceps) under natural and inoculated fermentation.

Due to the uncontrolled fermentation process and unstable quality of naturally fermented leaf mustard, inoculated fermentation is receiving more attention. Here, the physicochemical properties, volatile compounds, and microbial community in leaf mustard under natural fermentation (NF) and inoculated fermentation (IF) were analyzed and compared. The contents of total acid, crude fiber, and nitrite of leaf mustard were measured. Headspace-solid phase microextraction-gas chromatography-mass spectrometry and orthogonal projection on latent structure-discriminant analysis were used to analyze the differences of volatile compounds in NF and IF leaf mustard. Moreover, Illumina MiSeq high-throughput sequencing technology was employed to reveal the composition of microbiota. The results showed that the nitrite content in leaf mustard after IF (3.69 mg/kg) was significantly lower than that after NF (4.43 mg/kg). A total of 31 and 25 kinds of volatile components were identified in IF and NF, respectively. Among the detected compounds, 11 compounds caused the differences between IF and NF leaf mustard. The results of inter-group difference analysis showed that there were significant differences in fungal flora between IF and NF samples. Saccharomycetes, Kazachstania, and Ascomycota were the landmark microorganisms in IF leaf mustard and the landmark microorganisms in NF were Mortierellomycota, Sordariomycetes, and Eurotiomycetes. The abundance of probiotics (such as Lactobacillus) in IF leaf mustard (51.22%) was higher than that in NF (35.20%) and the abundance of harmful molds (such as Mortierella and Aspergillus) was opposite. Therefore, IF leaf mustard showed the potential to reduce the content of nitrite and harmful molds and increase the beneficial volatile compounds and probiotics. PRACTICAL APPLICATION: Leaf mustard of inoculated fermentation (IF) showed better fermented characteristics than natural fermentation in terms of lower nitrite content, greater beneficial volatile substances, and better potential for increasing probiotics and reducing harmful molds. These results provided a theoretical basis for IF leaf mustard and contributed to the industrial production of fermented leaf mustard.

Investigating the active chemical constituents and pharmacology of Nanocnide lobata in the treatment of burn and scald injuries.

OBJECTIVE: To identify the most effective fraction of Nanocnide lobata in the treatment of burn and scald injuries and determine its bioactive constituents. METHODS: Chemical identification methods were used to analyze solutions extracted from Nanocnide lobata using petroleum ether, ethyl acetate, n-butanol using a variety of color reactions. The chemical constituents of the extracts were identified by ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS). A total of 60 female mice were randomly divided into the following 6 groups: the petroleum ether extract-treated group; the ethyl acetate extract-treated group; the n-butanol extract-treated group; the model group; the control group; and the positive drug group. The burn/scald model was established using Stevenson's method. At 24 hours after modeling, 0.1 g of the corresponding ointment was evenly applied to the wound in each group. Mice in the model group did not undergo treatment, while those in the control group received 0.1 g of Vaseline. Wound characteristics, including color, secretions, hardness, and swelling, were observed and recorded. Photos were taken and the wound area calculated on the 1st, 5th, 8th, 12th, 15th, 18th and 21st days. Hematoxylin-eosin (HE) staining was utilized to observe the wound tissue of mice on the 7th, 14th, and 21st days. An enzyme-linked immunosorbent assay (ELISA) kit was used to measure the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß1. RESULTS: The chemical constituents of Nanocnide lobata mainly include volatile oils, coumarins, and lactones. UPLC-MS analysis revealed 39 main compounds in the Nanocnide lobata extract. Among them, ferulic acid, kaempferitrin, caffeic acid, and salicylic acid have been confirmed to exhibit anti-inflammatory and antioxidant activity related to the treatment of burns and scalds. HE staining revealed a gradual decrease in the number of inflammatory cells and healing of the wounds with increasing time after Nanocnide lobata extract administration. Compared with the model group, the petroleum ether extract-treated group showed significant differences in the levels of TNF-α (161.67±4.93, 106.33±3.21, 77.67±4.04 pg/mL) and IL-10 (291.77±4.93, 185.09±9.54, 141.33±1.53 pg/mL) on the 7th, 14th, and 21st days; a significant difference in the content of TGF-ß1 (75.68±3.06 pg/mL) on the 21st day; and a significant difference in the level of VEGF (266.67±4.73, 311.33±10.50 pg/mL) on the 7th and 14th days respectively. CONCLUSION: Petroleum ether Nanocnide lobata extract and the volatile oil compounds of Nanocnide lobata might be effective drugs in the treatment of burn and scald injuries, as they exhibited a protective effect on burns and scalds by reducing the expression of TNF-α, IL-10 and TGF-ß1 and increasing the expression of VEGF. In addition, these compounds may also exert pharmacological effects that promote wound tissue repair, accelerate wound healing, and reduce scar tissue proliferation, inflammation and pain.

Effects of Curcumin and Soy Isoflavones on Genomic Instability of Human Colon Cells NCM460 and SW620.

Curcumin (CUR) and soy isoflavones (SIs) are two plant-based polyphenols that have attracted much attention, because of their extensive anticancer and health maintenance effects. However, the relevant molecular mechanisms are still uncertain. Genomic instability (GIN) refers to a combination of gene abnormal amplification, sequence deletion, ectopic, and other types of gene damage in cells, and it is one of the main factors causing cells to lose normal physiological functions. Therefore, we used the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay as the main research method to analyze the effects of CUR and SIs on the GIN of human normal colon cells NCM460 and colon cancer cells SW620. Results show that CUR (12.5 µM) could reduce the apoptosis of NCM460 and maintain its genomic stability while inhibiting the proliferation of SW620 and promoting its apoptosis. There was no difference in the promoting effect of GIN between SW620 and NCM460 using SIs (3.125-50 µM). When the two polyphenols (v/v = 1/1, 1.5625-6.25 µM) were mixed, they could promote the proliferation and GIN of the NCM460 and SW620 cells, but we did not find that combining the two produced a better effect on the cells. In conclusion, CUR has more prominent health and anticancer effects, and it may become a dietary recommendation for daily health maintenance and a potential adjuvant drug for cancer treatment.

Colored Silicon Heterojunction Solar Cells Exceeding 23.5% Efficiency Enabled by Luminescent Down-Shift Quantum Dots.

Colored solar panels, realized by depositing various reflection layers or structures, are emerging as power sources for building with visual aesthetics. However, these panels suffer from reduced photocurrent generation due to the less efficient light harvesting from visible light reflection and degraded power conversion efficiency (PCE). Here, color-patterned silicon heterojunction solar cells are achieved by incorporating luminescent quantum dots (QDs) with high quantum yields as light converters to realize an asthenic appearance with high PCE. It is found that large bandgap (blue) QD layers can convert UV light into visible light, which can notably alleviate the parasitic absorption by the front indium tin oxide and doped amorphous silicon. Additionally, a universal optical path model is proposed to understand the light transmission process, which is suitable for luminescent down-shift devices. In this study, solar cells with a PCE exceeding 23.5% are achieved using the combination of a blue QD layer and a top low refractive index anti-reflection layer. Based on our best knoledge,the obtained PCE is the highest for a color-patterned solar cell. The results suggest an enhanced strategy involving incorporation of luminescent QDs with an optical path design for high-performance photovoltaic panels with visual aesthetics.

Research on the reform of position setting and performance evaluation in medical research institutes under the background of institute integration / 中华医学科研管理杂志

Objective:To explore the collaborative innovation development mechanism of hospitals and research institutes, fully integrate the institute personnel with hospitals, and conduct classified management and performance appraisal, promoting the integrated development of hospitals and research institutes.Methods:The idea of personnel classification, the establishment of an integrated research team, and technical team groupings and service directions were determined through key informant interviews, research ability and technical strength surveys, and other research methods; The performance appraisal scheme of research teams were established by using literature analysis and optimization and Delphi expert investigation; The platform team assessment programs were established by qualitative research methods.Results:Built a position setting framework for research institutes, formed hospital-institute integrated research teams around the hospital's clinical advantageous disciplines with researchers and clinical staff, set up platform teams based on existing equipment and technicians′ specialties, established a performance appraisal scheme for research teams based on Science and Technology Evaluation Metrics(STEM), determined a full-dimensional comprehensive performance evaluation scheme for the technology platforms based on service volume and quality.Conclusions:This study formulated a set of position setting and performance evaluation schemes that fit with the current situation of municipal research institutes, and explored a new scientific research cooperation mechanism of resource sharing, team co-construction, and technology sharing, which can provide a certain reference value for the reform of other medical research institutes.

Analysis of peripheral blood lymphocyte status in low-level-viremia patients with chronic hepatitis B virus infection after nucleos(t)ide analogue treatment / 中华微生物学和免疫学杂志

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Clinical characteristics of hospitalized premenopausal patients with hyperuricemia / 中华全科医师杂志

Objective:To analyze the clinical characteristics of hospitalized premenopausal patients with hyperuricemia.Methods:The medical records of premenopausal women with hyperuricemia (serum uric acid ≥360 μmol/L during hospitalization) admitted in Peking Union Medical College Hospital from 2013 to 2018 were reviewed and the clinical data were analyzed.Results:A total of 2 099 patients were enrolled. Only 14.01% (294 cases) of the patients were concerned about hyperuricemia by physicians. Autoimmune diseases (32.11%, 674 cases), nephrotic disease (19.29%, 405 cases) and endocrine system diseases (9.72%, 204 cases) are the main reasons for hospitalization, while 6.34%(133 cases) of patients were in gestation. In terms of the etiology, renal diseases (49.35%, 1 035 cases), specific drug use (49.26%, 1 034 cases) were the main causes of secondary hyperuricemia in premenopausal women, followed by metabolic diseases (10.62%, 233 cases). There was no significant difference in serum uric acid level among premenopausal women of different ages ( H=4.47, P=0.107), but the etiology of hyperuricemia among patients of different ages had significant differences. The proportion of hyperuricemia in patients with cancer and metabolic syndrome,secondary to use of diuretics and anti-tuberculosis drugs had differences among different age groups ( χ2=90.96,52.89,19.26 and 6.41, P<0.05). Conclusion:Hyperuricemia is not uncommon in premenopausal women. There are many secondary factors leading to hyperuricemia in premenopausal women, among which drugs and renal lesions are the main causes. In addition, the secondary factors in women with hyperuricemia has differences among different age groups.

Production of limonene and its derivative in Saccharomyces cerevisiae via metabolic engineering / 生物工程学报

Limonene and its derivative perillic acid are widely used in food, cosmetics, health products, medicine and other industries as important bioactive natural products. However, inefficient plant extraction and high energy-consuming chemical synthesis hamper the industrial production of limonene and perillic acid. In this study, limonene synthase from Mentha spicata was expressed in Saccharomyces cerevisiae by peroxisome compartmentalization, and the yield of limonene was 0.038 mg/L. The genes involved in limonene synthesis, ERG10, ERG13, tHMGR, ERG12, ERG8, IDI1, MVD1, ERG20ww and tLS, were step-wise expressed via modular engineering to study their effects on limonene yield. The yield of limonene increased to 1.14 mg/L by increasing the precursor module. Using the plasmid with high copy number to express the above key genes, the yield of limonene significantly increased up to 86.74 mg/L, which was 4 337 times higher than that of the original strain. Using the limonene-producing strain as the starting strain, the production of perillic acid was successfully achieved by expressing cytochrome P450 enzyme gene from Salvia miltiorrhiza, and the yield reached 4.42 mg/L. The results may facilitate the construction of cell factory with high yield of monoterpene products by S. cerevisiae.

Effect of chronic restraint stress on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice / 解剖学报

Objective To explore the effect of chronic restraint stress (CRS) on the phenotypic transition of hippocampal astrocytes and depression-like behavior in mice. Methods Forty eight male C57BL/6 mice were randomly divided into control groups (control), model groups (CRS) and fluoxetine(FLX) drug intervention groups (CRS+FLX), 16 for each group. The mice of the CRS group were subjected to 3 weeks chronic restraint stress. The mice of CRS + FLX group were treated with fluoxetine by intraperitoneal injection 30 minutes before restraint stress from the day 8 to day 21.

Effects of transient receptor potential vanilloid 4 inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide / 解剖学报

Objective To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) inhibitor HC067047 on anxiety-like behavior in mice induced by lipopolysaccharide (LPS). Methods Totally 48 male C57BL/6 mice were randomly divided into control group (NS), model group (LPS) and drug intervention group (HC + LPS). Anxiety mouse model was established by intraperitoneal injection of 0.83 mg/kg LPS. The HC + LPS group was intraperitoneally injected with HC067047 (10 mg/kg) 30 minutes before LPS injection, and the NS group and LPS group were injected with equal volume of normal saline. Open field test and social interaction experiments were used to detect anxiety-like behaviors in each group of mice; Immunohistochemical chemistry and Western blotting were used to detect the expression of TRPV4, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) in the hippocampus. Results Immunohistochemical and Western blotting experiments showed that, compared with the NS group, the expression of TRPV4 in the hippocampus of the LPS group was significantly up-regulated (P<0.0001); In the open field test, compared with the NS group, the total distance (P < 0.0001), the distance in the central area (P<0.01) and the time of in the central area mice in the LPS group reduced significantly (P< 0.01). HC067047 intervention reversed the activities of LPS model mice total distance (P < 0.05), the distance of activities in the central area (P < 0.001) and the time of in the central area (P < 0.01); In the social interaction test, compared with the NS group, the interaction time the unfamiliar mice reduced significantly in LPS group (P<0.01), which was reversed by HC067047 treatment (P< 0.01); Western blotting detection revealed that the expression of hippocampal iNOS (P<0.05), nNOS (P < 0.001), and eNOS (P < 0.001) in the LPS group were significantly higher than the NS group, which reduced remarkably by HC067047 treatment (iNOS P < 0.05, nNOS P < 0.01 and eNOS P < 0.01). Conclusion Inhibiting the expression of TRPV4 can improve the anxiety-like behavior, and this process may be related to anti-oxidative stress.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.