Associations between single nucleotide polymorphisms of cytokines and hepatitis B virus-related liver cirrhosis: A case-control study.

BACKGROUND AND AIMS: Various inflammatory and immune cytokines play key roles in the progression of hepatitis B virus (HBV)-related liver cirrhosis (LC). This study explored the relationship between single nucleotide polymorphisms (SNPs) in cytokines with the combined effect of polymorphisms and gender-polymorphisms interaction and LC risk. METHODS: In this study, a case-control design was used, samples were selected from 45 patients with hepatitis B-related cirrhosis and 45 age-gender-matched chronic HBV-infected patients without cirrhosis attending the tumor hospital of Wuwei Academy of Medical Sciences. Fifteen SNPs were examined using a real-time polymerase chain reaction allelic discrimination system. Logistic regression was utilized to assess cytokine-associated SNPs and the association between SNPs and LC progression in HBV-infected patients. RESULTS: The multivariate-adjusted logistic model revealed that the GG/AG dominant model (OR, 16.38; 95% CI, 1.13-236.70) and G allele (OR, 5.93; 95% CI, 0.98-36.01) of rs1800896 were associated with an increased risk of cirrhosis in CHB patients. Instead, rs2227306 CT presented a reduced cirrhosis risk (OR, 0.22; 95% CI, 0.04-1.38). Rs2055979 AA/AC was negatively associated with the risk of cirrhosis, potentially reversed in males (p = 0.021). Rs1799964 CC/CT was positively related to the risk of cirrhosis but reduced the risk of cirrhosis in males (OR, 0.13; 95% CI, 0.022-0.808; p = 0.028). Both rs1799964 TT and rs1799724 CT/TT genotype showed a synergistic effect in reducing the risk of cirrhosis with rs1800896 AA (OR, 0.08; 95% CI, 0.01-1.43 and OR, 0.12; 95% CI, 0.01-2.21). CONCLUSION: Polymorphisms rs1800896 and rs2227306 are potentially associated with the risk of cirrhosis. For the first time, the study highlights that the rs2055979 AA/AC and rs1799964 CC/CT polymorphism interact with gender and its potential reversal of cirrhosis risk in males. Furthermore, rs1800896 AA showed a synergistic effect with rs1799964 TT and rs1799724 CT/TT to prevent the progression of HBV infection to cirrhosis.

Correlation between macular perfusion status and visual acuity in retinal vein occlusion. / è§†ç½‘è†œé™è„‰é˜»å¡žåˆå¹¶é»„æ–‘çŒæ³¨çŠ¶æ€ä¸è‰¯ä¸Žè§†åŠ›çš„ç›¸å ³æ€§.

OBJECTIVES: Retinal vein occlusion (RVO) is the second most common retinal vascular disease worldwide, and the retinal perfusion status is closely related to the prognosis of the disease. Macular perfusion status is particularly correlated with visual acuity. This study aims to investigate the changes in macular perfusion indicators in RVO using optical coherence tomography angiography (OCTA) and analyze the correlation between macular perfusion status and visual acuity. METHODS: This cross-sectional study included 41 RVO patients, who were divided into 2 groups based on the occlusion site: 18 cases in the central retinal vein occlusion (CRVO) group and 23 cases in the branch retinal vein occlusion (BRVO) group. Additionally, they were categorized into ischemic RVO (23 cases) and non-ischemic RVO (16 cases) groups based on the presence of ischemia (2 eyes were excluded due to hemorrhage obscuring the peripheral retina, making it impossible to confirm the area of non-perfusion). A control group of 29 healthy individuals matched by sex and age was also recruited. Macular perfusion indicators were measured using OCTA, and the correlation between macular perfusion status and visual acuity was analyzed. RESULTS: Compared with healthy eyes, RVO eyes showed an increased foveal avascular zone (FAZ) area and significantly reduced superficial and deep vessel density (P<0.001). However, there were no significant differences in central foveal thickness (CFT) or macular perfusion indicators between the CRVO and BRVO groups (P>0.05). The best corrected visual acuity (BCVA) at the logarithm of the minimum angle of resolution (logMAR BCVA) was significantly negatively correlated with both superficial and deep retinal vessel density in RVO eyes (unstandardized coefficient B=-0.039, B=-0.042; P=0.017, P=0.040). The average BCVA in the ischemic RVO group was significantly worse than that in the non-ischemic RVO group (0.82±0.44 vs 0.45±0.29, P=0.007). The ischemic RVO group also had a larger FAZ area (P=0.003) and lower superficial and deep retinal vessel density (P<0.001, P=0.008, respectively) compared with the non-ischemic RVO group. The severity of macular ischemia did not correspond directly with the peripheral ischemia severity in RVO. CONCLUSIONS: Macular perfusion status is significantly reduced in RVO eyes compared to healthy eyes, which negatively impacts and limits visual acuity in RVO patients. Eyes with ischemic RVO have poorer visual acuity and macular perfusion status than those with non-ischemic RVO. OCTA is advantageous for observing vascular morphology and quantifying macular perfusion status, making it an effective tool for assessing disease progression.

Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing.

Cholangiocarcinoma (CCA) is a bile duct malignancy with a dismal prognosis. This study systematically investigated the role of the ribosomal protein S6 (RPS6) gene, which is dependent in CCA. We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis. Functional investigations have shown that alterations in RPS6 expression, both gain- and loss-of function could affect the proliferation of CCA cells. In xenograft tumor models, RPS6 overexpression enhances tumorigenicity, whereas RPS6 silencing reduces it. Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle, especially DNA replication. Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6. Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing (AS) events, and combined with RNA immunoprecipitation sequencing, revealed that minichromosome maintenance complex component 7 (MCM7) binds to RPS6, which regulates its AS and increases oncogenic activity in CCA. Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer (V-PMO) significantly inhibited the growth of CCA cells, patient-derived organoids, and subcutaneous xenograft tumor. Taken together, the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

Clinical and genetic features of Fanconi anemia associated with a variant of FANCA gene: Case report and literature review.

RATIONALE: Fanconi anemia (FA) is a hereditary disease caused by mutations in the genes involved in the DNA damage repair pathway. The FANCA gene is the most commonly pathogenic gene, accounting for more than 60% of all causative genes. PATIENT CONCERNS: The clinical case is a 3-year-old boy showed mild anemia and scattered bleeding spots the size of a needle tip all over his body. DIAGNOSES: Compound heterozygous mutation was identified in the FANCA gene in the FA case: c.1A > T from the father in exon 1; the deletion of chr16: 89857810-89858476 (exon13-14 del) from the mother; finally, the patient was diagnosed as Fanconi anemia. INTERVENTION: After diagnosis, the child received chemotherapy (Ara-C + Flu + Cy + ATG). Then, the hematopoietic stem cell transplantation and unrelated umbilical cord blood transfusion were performed. OUTCOMES: The child is recovering well and is in regular follow-up. CONCLUSION AND LESSONS: The discovery of new mutations in the FANCA gene enriches the genetic profile of FA and helps clinicians to further understand this disease and guide genetic counseling and prenatal diagnosis. Whole-exome sequencing is a powerful tool for diagnosing FA.

Five Volts Lithium Batteries with Advanced Carbonate-Based Electrolytes: A Rational Design via a Trio-Functional Addon Materials.

Lithium metal batteries paired with high-voltage LiNi0.5Mn1.5O4 (LNMO) cathodes are a promising energy storage source for achieving enhanced high energy density. Forming durable and robust solid-electrolyte interphase (SEI) and cathode-electrolyte interface (CEI) and the ability to withstand oxidation at high potentials are essential for long-lasting performance. Herein, advanced electrolytes are designed via trio-functional additives to carbonate-based electrolytes for 5 V Li||LNMO and graphite||LNMO cells achieving 88.3% capacity retention after 500 charge-discharge cycles. Theoretical calculations reveal that adding adiponitrile facilitates the presence of more hierarchical DFOB- and PF6 - dual anion structure in the solvation sheath, leading to a faster de-solvation of the Li cation. By combining both fluorine and nitrile additives, an efficient synergistic effect is obtained, generating robust thin inorganic SEI and CEI films, respectively. These films enhance microstructural stability; Li dendrite growth on the Li electrode is being suppressed at the anode side and transition-metals dissolution from the cathode is being mitigated, as evidenced by cryo-transmission electron microscopy and synchrotron studies.

Serum Lipoprotein(a) as Predictive Factor for Early Neurological Deterioration of Acute Ischemic Stroke After Thrombolysis.

Objective: This study aimed to explore the relationship between serum lipoprotein(a) (LP(a)) levels and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) after thrombolysis. Methods: In total, 236 patients with AIS after thrombolysis were enrolled in this study. Serum LP(a) levels were measured on admission after thrombolysis. END was defined as an increase of at least two points in the NIHSS score within 48 hours after thrombolysis. Binary logistic regression analysis was used to assess the association between serum LP(a) levels and END. Results: Overall, patients with END had higher LP(a) than those without END (high LP(a): 38.3% vs 22.2%, intermediate LP(a): 40.3% vs 41.8%, low LP(a): 21.3% vs 36.0%, p<0.005). In the multivariate analysis, high LP(a) (defined as LP(a) level≥ 300 mg/L) was an independent risk factor for END post-thrombolysis (OR=3.154, 95% CI=1.067-9.322, p=0.038). Conclusion: Our findings demonstrated that LP(a) was an independent risk factor for END post-thrombolysis and that LP(a) level≥ 300 mg/L could be associated with END post-thrombolysis in this study population.

Physicochemical properties, antioxidant and antidiabetic activities of different hydrolysates of goat milk protein.

There is growing interest in the origin, preparation, and application of bioactive peptides. This study investigated the impact of 6 enzymes on the structural, physicochemical properties, antioxidant activities, and antidiabetic potential of defatted fresh goat milk. Structural and functional changes resulting from enzymatic hydrolysis were assessed using gel electrophoresis, laser particle size analysis, multi-spectroscopy, and evaluations of foaming and emulsification properties. Antioxidant capacity was determined through free radical scavenging, Fe2+ chelation, and reducing ability experiments. Additionally, the inhibitory effects of the hydrolysates on α-glucosidase and α-amylase were measured to evaluate antidiabetic activity. Results showed that enzymatic hydrolysis disrupted the spatial structure of goat milk protein and reduced its molecular weight. Papain hydrolysate exhibited the highest degree of hydrolysis (32.87 ± 0.11%) and smallest particle size (294.75 ± 3.33 nm), followed by alcalase hydrolysate (29.12 ± 0.09%, 302.03 ± 7.28 nm). Alcalase hydrolysate showed the best foaming properties, while papain hydrolysate demonstrated the strongest DPPH and hydroxyl radical scavenging activity, Fe2+ chelation, and antidiabetic potential. These findings provide solid theoretical basis for utilizing defatted goat milk as functional ingredients or excipients in the food, medical, and cosmetic industries.

Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Moving toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1, and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7 with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10-5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via the sequestration of bio-relevant metal ions (i.e., Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared with that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

Genome-wide analysis of the NYN domain gene family in Brassica napus and its function role in plant growth and development.

The NYN domain gene family consists of genes that encode ribonucleases that are characterized by a newly identified NYN domain. Members of the family were widely distributed in all life kingdoms and play a crucial role in various RNA regulation processes, although the wide genome overview of the NYN domain gene family is not yet available in any species. Rapeseed (Brassica napus L.), a polyploid model species, is an important oilseed crop. Here, the phylogenetic analysis of these BnaNYNs revealed five distinct groups strongly supported by gene structure, conserved domains, and conserved motifs. The survey of the expansion of the gene family showed that the birth of BnaNYNs is explained by various duplication events. Furthermore, tissue-specific expression analysis, protein-protein interaction prediction, and cis-element prediction suggested a role for BnaNYNs in plant growth and development. Interestingly, the data showed that three tandem duplicated BnaNYNs (TDBs) exhibited distinct expression patterns from those other BnaNYNs and had a high similarity in protein sequence level. Furthermore, the analysis of one of these TDBs, BnaNYN57, showed that overexpression of BnaNYN57 in Arabidopsis thaliana and B. napus accelerated plant growth and significantly increased silique length, while RNA interference resulted in the opposite growth pattern. It suggesting a key role for the TDBs in processes related to plant growth and development.

Determination of calcium ß­hydroxy-ß-methylbutyrate content in special medical formula food and sports nutrition food by solid-phase extraction and high performance liquid chromatography.

Calcium ß­hydroxy-ß-methylbutyrate (CaHMB) can promote muscle growth, prevent muscle atrophy, and enhance immunity, therefore, it is widely used as a nutritional supplement in special medical formula food and sports nutrition food. Many methods for the detection of CaHMB have been reported, but the pretreatment method for these reported literatures directly involves extraction using hydrochloric acid solution, without any purification steps. A method for accurately determining CaHMB in special medical formula food and sports nutrition food was established for the first time using solid-phase extraction (SPE) purification and high-performance liquid chromatography method (HPLC). The samples were extracted and precipitated protein using methanol-water solution, purified using SPE method and analyzed by HPLC on diode array detector (DAD) mode under external standard method. The method obtained excellent calibration linearity (r2>0.9993) and a satisfactory analysis of the targeted compound, which were evaluated with calibration standards over the range of 0.020-2.00 mg/mL. The limit of quantifications (LOQs), which defined as the lowest spiking level, were set at 0.4 g/100 g (special medical formula food) and 1.0 g/100 g (sports nutrition food). The average recoveries were within 92.9-104% for the analytes, and the relative standard deviations (RSDs) were below 3.93%, measured at low, medium, and high concentrations. Moreover, the positive sample analysis results indicated that CaHMB was detected on 10 real special medical formula food and sports nutrition food products, the contents of which were generally consistent with their labeled values, with measured values ranging from 97.1 % to 119 % of the labeled values. These results suggested that the developed highly sensitive and specific method is highly feasible for monitoring of the target analyte in special medical formula food and sports nutrition food.

Chirality Sensing of Amino Acid Esters by S-2-Methylbutanamido-Substituted m-Phthalic Diamide-Linked Zinc Bisporphyrinate.

To understand the role of an additional coordination site in the linker in chirality sensing, we designed and synthesized an S-2-methylbutanamido-substituted m-phthalic diamide-linked zinc bisporphyrinate, [Zn2(S-MAABis)] and investigated its ability to sense the chirality of amino acid esters. The 1H NMR spectra and the crystal structure showed that the amido oxygen adjacent to the chiral carbon was coordinated with zinc. NMR and UV-vis titration showed that the binding of [Zn2(S-MAABis)] to amino acid esters occurred via two equilibria, forming 1:1 and 1:2 host-guest complexes. The CD spectra suggested that [Zn2(S-MAABis)] can effectively recognize the absolute configuration of amino acid esters. The sign of the CD spectra remained unchanged during the titration, indicating that the corresponding 1:1 and 1:2 host-guest complexes had the same chirality. This is different from previously studied amino-substituted m-phthalic diamide-linked zinc bisporphyrinate [Zn2(AmBis)], which showed chirality inversion during titration. Theoretical calculations indicated that the additional coordination sites (amido or amino) in the 1:1 host-guest complexes played different roles, leading to differences in chirality. Our studies suggest that the introduction of a coordination site can influence the chirality transfer process, but the results of chirality transfers are dependent on the specific binding modes.

Elucidating the role of genetically determined metabolites in Diabetic Retinopathy: insights from a mendelian randomization analysis.

AIMS: Diabetic retinopathy (DR) results from complex genetic and metabolic interactions. Unraveling the links between blood metabolites and DR can advance risk prediction and therapy. METHODS: Leveraging Mendelian Randomization (MR) and Linkage Disequilibrium Score Regression (LDSC), we analyzed 10,413 DR cases and 308,633 controls. Data was sourced from the Metabolomics GWAS server and the FinnGen project. RESULTS: Our research conducted a comprehensive MR analysis across 486 serum metabolites to investigate their causal role in DR. After stringent selection and validation of instrumental variables, we focused on 480 metabolites for analysis. Our findings revealed 38 metabolites potentially causally associated with DR. Specifically, 4-androsten-3beta,17beta-diol disulfate 2 was identified as significantly associated with a reduced risk of DR (OR = 0.471, 95% CI = 0.324-0.684, p = 7.87 × 10- 5), even after rigorous adjustments for multiple testing. Sensitivity analyses further validated the robustness of this association, and linkage disequilibrium score regression analyses showed no significant genetic correlation between this metabolite and DR, suggesting a specific protective effect against DR. CONCLUSIONS: Our study identifies 4-androsten-3beta,17beta-diol disulfate 2, a metabolite of androgens, as a significant protective factor against diabetic retinopathy, suggesting androgens as potential therapeutic targets.

Impact of serum apolipoproteins on the prognosis of acute ischemic stroke after thrombolysis.

OBJECTIVE: The purpose of this study is to the relationship between peripheral apolipoproteins and the prognosis of patients with acute ischemic stroke (AIS) after thrombolysis. METHODS: A total of 231 AIS patients with thrombolysis was enrolled. Serum apolipoproteins were measured on admission after thrombolysis. All patients enrolled were followed up for 90 days. Their functional outcomes were assessed by the modified Rankin Scale (mRS). Good functional outcome was considered as mRS < 3. Logistic regression was applied to assess the association between serum apolipoproteins and the mRS at 90 days. RESULTS: In multivariate analysis,1) ApoB (OR=0.099, 95%CI=0.017∼0.575, p=0.010) and ApoB/ApoA-1(OR=0.113, 95%CI=0.015∼0.868, p=0.036) were independent risk factors of good functional outcome at 90 days. 2). there were significant differences in the mRS score distribution at 90 days in groups according to the ROC cutoff values of ApoB (0.85g/L) and ApoB/ApoA-1 ratio (0.61) (all p<0.05). CONCLUSION: Our findings demonstrated ApoB and ApoB/apoA-1 ratio were independent risk factors for good functional outcome at 90 days, and the ApoB level below 0.85g/L and ApoB/ApoA-1 ratio below 0.61 could be associated with a better functional outcome in this study population.

Reverse Hydrogen Spillover on Metal Oxides for Water-Promoted Catalytic Oxidation Reactions.

Understanding the water-involved mechanism on metal oxide surface and the dynamic interaction of water with active sites is crucial in solving water poisoning in catalytic reactions. Herein, this work solves this problem by designing the water-promoted function of metal oxides in the ethanol oxidation reaction. In situ multimodal spectroscopies unveil that the competitive adsorption of water-dissociated *OH species with O2 at Sn active sites results in water poisoning and the sluggish proton transfer in CoO-SnO2 imparts water-resistant effect. Carbon material as electron donor and proton transport channel optimizes the Co active sites and expedites the reverse hydrogen spillover from CoO to SnO2. The water-promoted function arises from spillover protons facilitating O2 activation on the SnO2 surface, leading to crucial *OOH intermediate formation for catalyzing C-H and C-C cleavage. Consequently, the tailored CoO-C-SnO2 showcases a remarkable 60-fold enhancement in ethanol oxidation reaction compared to bare SnO2 under high-humidity conditions.

The interfacial synergy of hierarchical FeCoNiP@FeNi-LDH heterojunction for efficient alkaline water splitting.

In response to the growing demand for clean, green, and sustainable energy sources, the development of cost-effective and durable high-activity overall water splitting electrocatalysts is urgently needed. In this study, the heterogeneous structure formed by the combination of FeCoNiP and FeNi-LDH was homogeneously dispersed onto CuO nanowires generated by in-situ oxidation of copper foam as a substrate using an electrodeposition method. This multilevel structure exhibits excellent bifunctional properties as an electrode material in alkaline solutions, for the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) only 206 mV and 147 mV overpotentials are needed to achieve a current density of 100 mA cm-2 respectively. Full water electrolysis is thus enabled to take place at such a low cell voltage as 1.64 V to reach the current density of 100 mA cm-2, which exhibits a long-term stability of 30 h. These improved electrocatalytic performances stem from the construction of multilevel structures. The X-ray photoelectron spectroscopy suggests that strong electron transfer occurs between heterogeneous structures, thus facilitating the OER and HER process. The dispersion of CuO nanowires not only increases the electrochemically active surface areas but also improves the overall hydrophilic and aerophobic properties. This work highlights the positive effect of multilevel structure in the design of more efficient electrocatalysts and provides a reference for the preparation of other low-cost, high-activity bifunctional electrocatalysts.

The superior allele LEA12OR in wild rice enhances salt tolerance and yield.

Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by rice to resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12OR, which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12OR, as the early regulator of the LEA12OR-OsSAPK10-OsbZIP86-OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12OR provides a new avenue for improving ST and yield via the application of LEA12OR in current rice through molecular breeding and genome editing.

The research on infrared radiation affected by smoke or fog in different environmental temperatures.

Infrared thermal imaging camera as a non-contact monitoring of the object to be measured is widely used in fire detection, driving assistance and so on. Although there are many related studies, there is a lack of research on the influence of fog or smoke on infrared imaging under different environmental temperatures. To address this shortcoming, The temperature of both the environment and the target in this experiment is controlled by PID technology. The smoke or fog environment is generated using a smoke cake or an ultrasonic fog machine. The temperature of the target was measured by infrared thermal imaging camera. It was observed that as the temperature of the environment increases, the measured temperature of the target also increases. However, the change in temperature is more pronounced in the fog environment compared to either the smoke environment or the normal environment. It has been found through research that environmental radiation causes temperature changes in fog droplets. Therefore, Infrared radiation is less affected in the smoke environment and more affected in the fog environment. Additionally, when the environmental temperature is close to the target's temperature, the infrared image becomes blurred.

Preliminary exploration of amide proton transfer weighted imaging in differentiation between benign and malignant bone tumors.

Purpose: To explore the value of 3D amide proton transfer weighted imaging (APTWI) in the differential diagnosis between benign and malignant bone tumors, and to compare the diagnostic performance of APTWI with traditional diffusion-weighted imaging (DWI). Materials and methods: Patients with bone tumors located in the pelvis or lower limbs confirmed by puncture or surgical pathology were collected from January 2021 to July 2023 in the First Affiliated Hospital of Zhengzhou University. All patients underwent APTWI and DWI examinations. The magnetization transfer ratio with asymmetric analysis at the frequency offset of 3.5 ppm [MTRasym(3.5 ppm)] derived by APTWI and the apparent diffusion coefficient (ADC) derived by DWI for the tumors were measured. The Kolmogorou-Smirnou and Levene normality test was used to confirm the normal distribution of imaging parameters; and the independent sample t test was used to compare the differences in MTRasym(3.5 ppm) and ADC between benign and malignant bone tumors. In addition, the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different imaging parameters in differentiation between benign and malignant bone tumors. P<0.05 means statistically significant. Results: Among 85 bone tumor patients, 33 were benign and 52 were malignant. The MTRasym(3.5 ppm) values of malignant bone tumors were significantly higher than those of benign tumors, while the ADC values were significantly lower in benign tumors. ROC analysis shows that MTRasym(3.5 ppm) and ADC values perform well in the differential diagnosis of benign and malignant bone tumors, with the area under the ROC curve (AUC) of 0.798 and 0.780, respectively. Combination of MTRasym(3.5 ppm) and ADC values can further improve the diagnostic performance with the AUC of 0.849 (sensitivity = 84.9% and specificity = 73.1%). Conclusion: MTRasym(3.5 ppm) of malignant bone tumors was significantly higher than that of benign bone tumors, reflecting the abnormal increase of protein synthesis in malignant tumors. APTWI combined with DWI can achieve a high diagnostic efficacy in differentiation between benign and malignant bone tumors.

Dimethyl fumarate ameliorates chronic stress-induced anxiety-like behaviors by decreasing neuroinflammation and neuronal activity in the amygdala.

BACKGROUND: Chronic stress-induced neuroinflammation plays a pivotal role in the development and exacerbation of mental disorders, such as anxiety and depression. Dimethyl Fumarate (DMF), an effective therapeutic agent approved for the treatment of multiple sclerosis, has been widely reported to display anti-inflammatory and anti-oxidative effects. However, the impact of DMF on chronic stress-induced anxiety disorders and the exact underlying mechanisms remain largely unknown. METHODS: We established a mouse model of chronic social defeat stress (CSDS). DMF was administered orally 1 h before daily stress session for 10 days in CSDS + DMF group. qRT-PCR and western blotting were used to analyze mRNA and protein expression of NLRP3, Caspase-1 and IL-1ß. Immunofluorescence staining was carried out to detect the expression of Iba 1 and c-fos positive cells as well as morphological change of Iba 1+ microglia. Whole-cell patch-clamp recording was applied to evaluate synaptic transmission and intrinsic excitability of neurons. RESULTS: DMF treatment significantly alleviated CSDS-induced anxiety-like behaviors in mice. Mechanistically, DMF treatment prevented CSDS-induced neuroinflammation by inhibiting the activation of microglia and NLRP3/Caspase-1/IL-1ß signaling pathway in basolateral amygdala (BLA), a brain region important for emotional processing. Furthermore, DMF treatment effectively reversed the CSDS-caused disruption of excitatory and inhibitory synaptic transmission balance, as well as the increased intrinsic excitability of BLA neurons. CONCLUSIONS: Our findings provide new evidence that DMF may exert anxiolytic effect by preventing CSDS-induced activation of NLRP3/Caspase-1/IL-1ß signaling pathway and alleviating hyperactivity of BLA neurons.

The BEL1-like homeodomain protein OsBLH4 regulates rice plant height, grain number, and heading date by repressing the expression of OsGA2ox1.

Gibberellins (GAs) play crucial roles in regulating plant architecture and grain yield of crops. In rice, the inactivation of endogenous bioactive GAs and their precursors by GA 2-oxidases (GA2oxs) regulates stem elongation and reproductive development. However, the regulatory mechanisms of GA2ox gene expression, especially in rice reproductive organs, are unknown. The BEL1-like homeodomain protein OsBLH4, a negative regulatory factor for the rice OsGA2ox1 gene, was identified in this study. Loss of OsBLH4 function results in decreased bioactive GA levels and pleiotropic phenotypes, including reduced plant height, decreased grain number per panicle, and delayed heading date, as also observed in OsGA2ox1-overexpressing plants. Consistent with the mutant phenotype, OsBLH4 was predominantly expressed in shoots and young spikelets; its encoded protein was exclusively localized in the nucleus. Molecular analysis demonstrated that OsBLH4 directly bound to the promoter region of OsGA2ox1 to repress its expression. Genetic assays revealed that OsBLH4 acts upstream of OsGA2ox1 to control rice plant height, grain number, and heading date. Taken together, these results indicate a crucial role for OsBLH4 in regulating rice plant architecture and yield potential via regulation of bioactive GA levels, and provide a potential strategy for genetic improvements of rice.