The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China.

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. OBJECTIVE: The objective of the study is to clarify the core features and influence factors of CRD patients in China. METHODS: Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. RESULTS: A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. CONCLUSIONS: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.

Histone deacetylase 9 plays a role in sevoflurane-induced neuronal differentiation inhibition by inactivating cAMP-response element binding protein transcription and inhibiting the expression of neurotrophin-3.

Postoperative cognitive decline (POCD) is a common and serious complication following anesthesia and surgery; however, the precise mechanisms of POCD remain unclear. Our previous research showed that sevoflurane impairs adult hippocampal neurogenesis (AHN) and thus cognitive function in the aged brain by affecting neurotrophin-3 (NT-3) expression; however, the signaling mechanism involved remains unexplored. In this study, we found a dramatic decrease in the proportion of differentiated neurons with increasing concentrations of sevoflurane, and the inhibition of neural stem cell differentiation was partially reversed after the administration of exogenous NT-3. Understanding the molecular underpinnings by which sevoflurane affects NT-3 is key to counteracting cognitive dysfunction. Here, we report that sevoflurane administration for 2 days resulted in upregulation of histone deacetylase 9 (HDAC9) expression, which led to transcriptional inactivation of cAMP-response element binding protein (CREB). Due to the colocalization of HDAC9 and CREB within cells, this may be related to the interaction between HDAC9 and CREB. Anyway, this ultimately led to reduced NT-3 expression and inhibition of neural stem cell differentiation. Furthermore, knockdown of HDAC9 rescued the transcriptional activation of CREB after sevoflurane exposure, while reversing the downregulation of NT-3 expression and inhibition of neural stem cell differentiation. In summary, this study identifies a unique mechanism by which sevoflurane can inhibit CREB transcription through HDAC9, and this process reduces NT-3 levels and ultimately inhibits neuronal differentiation. This finding may reveal a new strategy to prevent sevoflurane-induced neuronal dysfunction.

Metabolic profile of follicular fluid in patients with ovarian endometriosis undergoing IVF: a pilot study.

RESEARCH QUESTION: What are the metabolic characteristics of follicular fluid in patients with ovarian endometriosis undergoing IVF? DESIGN: This was an exploratory cohort study on endometriosis. In total, 19 infertile patients with ovarian endometriosis diagnosed by laparoscopy, and 23 controls matched in terms of age and body mass index (women with infertility due to male or tubal factors) were enrolled in this study. All patients underwent IVF treatment with a gonadotrophin-releasing hormone antagonist protocol, and follicular fluid was collected at oocyte retrieval. The metabolomics of follicular fluid samples was analysed using an ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). The best combination of biomarkers was selected by performing stepwise logistic regression analysis with backward elimination. RESULTS: Fifteen metabolites were identified as biomarkers associated with endometriosis. A final model containing 8-hydroxy-2-deoxyguanosine, biotin, n-acetyl-L-methionine and n-methylnicotinamide was constructed. Receiver operating characteristic analysis confirmed the value of these parameters in diagnosing endometriosis, with sensitivity of 94.7% and specificity of 95.7%. Enrichment analysis via the Kyoto Encyclopedia of Genes and Genome showed that 15 metabolites were enriched in eight metabolic pathways. CONCLUSION: Metabolomics based on UHPLC-OE-MS effectively characterized the metabolomics analysis of follicular fluid in patients with ovarian endometriosis. These findings may provide a new basis for better understanding of how diseases progress, and for the discovery of new biomarkers.

How does the SARS-CoV-2 reinfection rate change over time? The global evidence from systematic review and meta-analysis.

BACKGROUND: There is a significant increase in the number of SARS-CoV-2 reinfection reports in various countries. However, the trend of reinfection rate over time is not clear. METHODS: We searched PubMed, Web of Science, Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang for cohort studies, case-control studies, and cross-sectional studies up to March 16, 2023, to conduct a meta-analysis of global SARS-CoV-2 reinfection rate. Subgroup analyses were performed for age, country, study type, and study population, and time-varying reinfection rates of SARS-CoV-2 were estimated using meta-regression. The risk of bias was assessed using the Newcastle-Ottawa Scale and the Joanna Briggs Institute critical appraisal tool. RESULT: A total of 55 studies involving 111,846 cases of SARS-CoV-2 reinfection were included. The pooled SARS-CoV-2 reinfection rate was 0.94% (95% CI: 0.65 -1.35%). In the subgroup analyses, there were statistically significant differences in the pooled reinfection rates by reinfection variant, and study type (P < 0.05). Based on meta-regression, the reinfection rate fluctuated with time. CONCLUSION: Meta-regression analysis found that the overall reinfection rate increased and then decreased over time, followed by a period of plateauing and then a trend of increasing and then decreasing, but the peak of the second wave of reinfection rate was lower than the first wave. SARS-CoV-2 is at risk of reinfection and the Omicron variant has a higher reinfection rate than other currently known variants. The results of this study could help guide public health measures and vaccination strategies in response to the Coronavirus Disease 2019 (COVID-19) pandemic.

Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.

Feasibility Analysis of Individualized Low Flow Rate Abdominal Contrast-Enhanced Computed Tomography in Chemotherapy Patients: Dual-Source Computed Tomography With Low Tube Voltage.

PURPOSE: The aim of the study is to investigate the feasibility of using dual-source computed tomography (CT) combined with low flow rate and low tube voltage for postchemotherapy image assessment in cancer patients. METHODS: Ninety patients undergoing contrast-enhanced CT scans of the upper abdomen were prospectively enrolled and randomly assigned to groups A, B, and C (n = 30 each). In group A, patients underwent scans at 120 kVp with 448 mgI/kg. Patients in group B underwent scans at 100 kVp with 336 mgI/kg. Patient in group C underwent scans at 70 kVp with of 224 mgI/kg. Quantitative measurements including the CT number, standard deviation of CT number, signal-to-noise ratio, contrast-to-noise ratio, subjective reader scores, and the volume and flow rate of contrast agent were evaluated for each group. RESULTS: There was no statistically significant difference in the subjective image scores within the three groups except for the kidney (all P > 0.05). Group C showed significantly higher CT values, lower noise levels, and higher signal-to-noise ratio and contrast-to-noise ratio values in the majority of the regions of interest compared to the other groups (P < 0.05). In group C, the contrast agent dose was decreased by 46% compared to group A (79.48 ± 12.24 vs 42.7 ± 8.6, P < 0.01), and the contrast agent injection rate was reduced by 22% (2.7 ± 0.41 vs 2.1 ± 0.4, P < 0.01). CONCLUSIONS: The use of 70 kVp tube voltage combined with low iodine flow rates prove to be a more effective approach in solving the challenge of compromised blood vessels in postchemotherapy tumor patients, without reducing image quality and diagnostic confidence.

The degree of risk factor and accumulation effect for large niche in individuals after cesarean section.

BACKGROUND: The risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear. METHODS: Large niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation. RESULT(S): In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30-34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS. CONCLUSION(S): This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.

Agarose biodegradation by deep-sea bacterium Vibrio natriegens WPAGA4 with the agarases through horizontal gene transfer.

This study aimed to reveal the importance of horizontal gene transfer (HGT) for the agarose-degrading ability and the related degradation pathway of a deep-sea bacterium Vibrio natriegens WPAGA4, which was rarely reported in former works. A total of four agarases belonged to the GH50 family, including Aga3418, Aga3419, Aga3420, and Aga3472, were annotated and expressed in Escherichia coli cells. The agarose degradation products of Aga3418, Aga3420, and Aga3472 were neoagarobiose, while those of Aga3419 were neoagarobiose and neoagarotetraose. The RT-qPCR analysis showed that the expression level ratio of Aga3418, Aga3419, Aga3420, and Aga3472 was stable at about 1:1:1.5:2.5 during the degradation, which indicated the optimal expression level ratio of the agarases for agarose degradation by V. natriegens WPAGA4. Based on the genomic information, three of four agarases and other agarose-degrading related genes were in a genome island with a G + C content that was obviously lower than that of the whole genome of V. natriegens WPAGA4, indicating that these agarose-degrading genes were required through HGT. Our results demonstrated that the expression level ratio instead of the expression level itself of agarase genes was crucial for agarose degradation by V. natriegens WPAGA4, and HGT occurred in the deep-sea environment, thereby promoting the deep-sea carbon cycle and providing a reference for studying the evolution and transfer pathways of agar-related genes.

Nerve Distribution Method is Superior to the Conventional Method in BoNT-A Treatment of Trapezius Hypertrophy: A Randomized Controlled Trial.

The contour of the neck and shoulder is defined by the trapezius muscle (TM). Beyond facial procedures, botulinum toxin A (BoNT-A) injections has been increasingly adopted to create a smooth shoulder line. Several studies described the intramuscular nerve branching and the pattern of perforating branch of the accessory nerve in the trapezius muscle, providing essential information for botulinum neurotoxin injection. To this date, research groups seldom perform clinical investigations, especially randomized controlled trials, that demonstrates whether BoNT-A injections using the nerve distribution method for aesthetic purposes is more effective. Patients met the criteria for inclusion were randomized to either the Nerve Distribution group (ND group) or control group. Control group patients received injection using the conventional method while ND group patients received the nerve distribution method. Photographic and ultrasonographic evaluations were carried out at baseline, one month, three months, and six months after the procedure. Patients were also required to complete a questionnaire to evaluate their feedbacks to the injection. After screening, 30 healthy young Chinese women were included. At one-month follow-up, no statistically significant difference was observed between the two methods. At the three-month follow-up, the reduction of the TM thickness for the ND group (0.21 ± 0.09 cm) was more than that for the control group (0.27 ± 0.08 cm), with p = 0.047*. Similar differences were observed for the reduction of the shoulder area proportion (p = 0.031*) and the shoulder angle (p = 0.035*). At the six-month follow-up, the reduction in TM thickness in the ND group (0.2 ± 0.09 cm) was more than that of the control group (0.28 ± 0.06 cm), with p = 0.041*. The global aesthetic improvement scale feedbacks of the two methods showed no significant difference (3.4 ± 0.71 vs 3.8 ± 0.91, p = 0.207). The patients did not experience severe side effects. Compared to the conventional injection method, the nerve distribution method is more effective in reducing the trapezius muscle thickness, shoulder area proportion, and shoulder angle at three months, and shows longer lasting effects. The results of this study introduce unique insights into the design and tailoring of treatment protocols for shoulder-line contouring using BoNT-A.Level of Evidence I This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Ideal Chinese Lip: Impact of Lip Contours and Proportions.

BACKGROUND: The lips are one crucial determinant of facial attractiveness. Current studies investigating lip attractiveness were mostly conducted in Caucasians, and the results could not directly apply to Asians. Aside from lip proportions, lip contours play an important role in attractiveness but it is unclear how people perceive different lip contours. The aim of this study was to investigate the aesthetic perception of various lip shapes by Chinese to identify the most attractive lip morphology for women and men, respectively. METHODS: 303 Chinese participants were invited to rate the attractiveness of identical lip images with different contours and proportions in a young female and a young male. Stratified analyses were performed to assess the effect of gender, age and occupation on the preference of lip shapes. RESULTS: The lips that were rated to be most attractive had a flat upper vermilion border, an M-shaped oral fissure and a U-shaped lower vermilion border in both genders. Most respondents considered an upper-to-lower vermilion proportion of 1:1 to be more attractive, regardless of the gender of the lip models, and the lip thickness-to-width proportions of 1:2 and 1:2.5 were perceived most attractive for female and male, respectively. CONCLUSIONS: This study adds to our understanding of how lip contours contribute to attractiveness and that Chinese have distinctive aesthetic preferences for lip morphology, which possibly stem from racial characteristics and cultural differences. With such knowledge, practitioners may better tailor the treatment strategy when performing lip rejuvenation procedures. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

QTL Detection and Candidate Gene Identification for Eating and Cooking Quality Traits in Rice (Oryza sativa L.) via a Genome-Wide Association Study.

The eating and cooking quality (ECQ) directly affects the taste of rice, being closely related to factors such as gelatinization temperature (GT), gel consistency (GC) and amylose content (AC). Mining the quantitative trait loci (QTLs), and gene loci controlling ECQ-related traits is vital. A genome-wide association study on ECQ-related traits was conducted, combining 1.2 million single nucleotide polymorphisms (SNPs) with the phenotypic data of 173 rice accessions. Two QTLs for GT, one for GC and five for AC were identified, of which two were found in previously reported genes, and six were newly found. There were 28 positional candidate genes in the region of qAC11. Based on a linkage disequilibrium (LD) analysis, three candidate genes were screened within the LD region associated with AC. There were significant differences between the haplotypes of LOC_Os11g10170, but no significant differences were found for the other two genes. The qRT-PCR results showed that the gene expression levels in the accessions with high ACs were significantly larger than those in the accessions with low ACs at 35d and 42d after flowering. Hap 2 and Hap 3 of LOC_Os11g10170 reduced the AC by 13.09% and 10.77%, respectively. These results provide a theoretical and material basis for improving the ECQ of rice.

Comparing the mechanisms of syntrophic volatile fatty acids oxidation and methanogenesis recovery from ammonia stress in regular and biochar-assisted anaerobic digestion: Different roads lead to the same goal.

Biochar has been recognized as a promising additive to mitigate ammonia inhibition during syntrophic methanogenesis, while the key function of biochar in this process is still in debates. This study clarified the distinct mechanisms of syntrophic volatile fatty acids -oxidizing and methanogenesis recovery from ammonia inhibition in regular and biochar-assisted anaerobic digestion. Under 5 g/L ammonia stress, adding biochar shortened the methanogenic lag time by 10.9% and dramatically accelerated the maximum methane production rate from 60.3 to 94.7 mLCH4/gVSsludge/d. A photometric analysis with a nano-WO3 probe revealed that biochar enhanced the extracellular electron transfer (EET) capacity of suspended microbes (Pearson's r = -0.98), confirming that biochar facilitated methanogenesis by boosting EET between syntrophic butyrate oxidizer and methanogens. Same linear relationship between EET capacity and methanogenic rate was not observed in the control group. Microbial community integrating functional genes prediction analysis uncovered that biochar re-shaped syntrophic partners by enriching Constridium_sensu_stricto/Syntrophomonas and Methanosarcina. The functional genes encoding Co-enzyme F420 hydrogenase and formylmethanofuran dehydrogenase were upregulated by 1.4-2.3 times, consequently enhanced the CO2-reduction methanogenesis pathway. Meanwhile, the abundances of gene encoding methylene-tetrahydrofolate transformation, a series of intermediate processes involved in acetate oxidation, in the biochar-assisted group were 28.2-63.7% higher than these in control group. Comparatively, Methanosaeta played a pivotal role driving aceticlastic methanogenesis in the control group because the abundance of gene encoding acetyl-CoA decarbonylase/synthase complex increased by 1.9 times, suggesting an aceticlastic combining H2-based syntrophic methanogenesis pathway was established in control group to resist ammonia stress. A 2nd period experiment elucidated that although depending on distinct mechanisms, the volatile fatty acid oxidizers and methanogens in both groups developed sustained and stable strategies to resist ammonia stress. These findings provided new insights to understand the distinct methanogenic recovery strategy to resist toxic stress under varied environmental conditions.

Automated 3D Perioral Landmark Detection Using High-Resolution Network: Artificial Intelligence-Based Anthropometric Analysis.

BACKGROUND: 3D facial stereophotogrammetry, as a convenient, non-invasive and highly reliable evaluation tool, has shown great potential in pre-operative planning and treatment efficacy evaluation of plastic surgery in recent years. However, it requires manual identification of facial landmarks by trained evaluators to obtain anthropometric data, which consumes large amount of time and effort. Automatic 3D facial landmark localization may facilitate fast data acquisition and eliminate evaluator error. OBJECTIVES: In this paper, we propose a novel deep-learning method based on dimension-transformation and key-point detection for automated 3D perioral landmark annotation. METHODS: The 3D facial model is transformed into 2D images on which High-Resolution Network is implemented for key point detection. The 2D coordinates of key points are then mapped back to the 3D model using mathematical methods to obtain the 3D landmark coordinates. This program was trained with 120 facial models and validated in 50 facial models. RESULTS: Our approach achieved satisfactory accuracy of 1.30 ± 0.68 mm error in landmark detection with an average processing time of 5.2 ± 0.21 seconds per model. And subsequent analysis based on these landmarks showed an error of 0.87 ± 1.02 mm for linear measurements and 5.62 ± 6.61° for angular measurements. CONCLUSIONS: This automated 3D perioral landmarking method could serve as an effective tool that enables fast and accurate anthropometric analysis of lip morphology for plastic surgery and aesthetic procedures.

Deciphering Depressor Anguli Oris for Lower Face Rejuvenation: A Prospective Ultrasound-Based Investigation.

BACKGROUND: The depressor anguli oris muscle (DAO) is a pivotal treatment target in creation of harmonic jawline. However, evidence of its live morphology remains scarce. OBJECTIVES: This study aimed to reevaluate DAO by a facile ultrasound analysis and hereby guide safer and more effective botulinum toxin type A (BTX-A) injection. METHODS: A prospective ultrasound assessment was conducted in 41 patients. Morphology of DAO and its relative position with neighboring structures were appraised at the ubiquitous facial landmark, labiomandibular fold (LMF). Three-dimensional images were captured before and after receiving BTX-A injection based on sonographic evidence. RESULTS: The skin-to-muscle depths of DAO on average (measured from the medial to lateral border) were 5.26, 5.61, and 8.42 mm. DAO becomes thinner and wider from zone 1 to 3 (p < 0.001). Overlapping lengths between DAO and DLI increased from zone 1 to 3: 4.74, 9.68, 14.54 mm (p < 0.001). The medial border of DAO was located at 4.33, 6.12, 8.90 mm medial to LMF (zone 1-3), and no muscle fibers of DAO was observed at zone 1 and 2 in near one-third of patients. Mouth corner downturn angle improvement upon receiving BTX-A injection at zone 2 and 3 were 88.3%, 32.3%, and 14.7% for the neutral, maximum smile, and down-pulling mouth corner expressions. CONCLUSIONS: This work established an informative ultrasound portrait of the DAO and structures in the perioral region, which suggests LMF as a convenient landmark to locate DAO. Injections at the middle and lower thirds of LMF at a 4-5 mm depth is recommended.

Oncogenic LINC00857 recruits TFAP2C to elevate FAT1 expression in gastric cancer.

FAT atypical cadherin 1 (FAT1) is a mutant gene frequently found in human cancers and mainly accumulates at the plasma membrane of cancer cells. Emerging evidence has implicated FAT1 in the progression of gastric cancer (GC). This study intended to identify a regulatory network related to FAT1 in GC development. Upregulated expression of FAT1 was confirmed in GC tissues, and silencing FAT1 was observed to result in suppression of GC cell oncogenic phenotypes. Mechanistic investigation results demonstrated that FAT1 upregulated AP-1 expression by phosphorylating c-JUN and c-FOS, whereas LINC00857 elevated the expression of FAT1 by recruiting a transcription factor TFAP2C. Functional experiments further suggested that LINC00857 enhanced the malignant biological characteristics of GC cells through TFAP2C-mediated promotion of FAT1. More importantly, LINC00857 silencing delayed the tumor growth and blocked epithelial-mesenchymal transition in tumor-bearing mice, which was associated with downregulated expression of TFAP2C/FAT1. To conclude, LINC00857 plays an oncogenic role in GC through regulating the TFAP2C/FAT1/AP-1 axis. Therefore, this study contributes to extended the understanding of gastric carcinogenesis and LINC00857 may serve as a therapeutic target for GC.

Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice.

BACKGROUND: Some patients show persistent cognitive decline for weeks, months or even years after surgery, which seriously affects their long-term prognosis and quality of life. However, most previous basic studies have focused mainly on the mechanisms of early postoperative cognitive decline, whereas cognitive decline in the longer term after surgery is less well-understood. The subgranular zone of the dentate gyrus exhibits life-long neurogenesis, supporting hippocampus-dependent learning and memory. MAIN TEXT: The aim of this study was to investigate whether adult hippocampal neurogenesis (AHN) involves in cognitive decline later following surgery and to further explore the roles of CD8 + T lymphocytes infiltrating the hippocampal parenchyma after surgery in this pathological process. Cognitive function was examined in adult mice that underwent laparotomy combined with partial hepatectomy, and the results showed that cognitive decline persisted in mice who underwent surgery during the first postoperative month, even though there was a trend toward continuous improvement over time. Significantly decreased numbers of DCX + cells, BrdU + cells, and BrdU + /DCX + cells were observed on day 8 after surgery, and a significantly decreased number of NeuN + /BrdU + cells was observed on day 28 after surgery, which indicated inhibition of AHN. After surgery, T lymphocytes, the majority of which were CD8 + T cells, infiltrated the hippocampus and secreted Interferon-γ (IFN-γ). Depletion of CD8 + T cells could inhibit the increase of IFN-γ synthesis, improve hippocampal neurogenesis, and improve postoperative cognitive function. Hippocampal microinjection of IFN-γ neutralizing antibody or adeno-associated virus to knock down IFN-γ receptor 1 (IFNGR1) could also partially attenuate the inhibition of AHN and improve postoperative cognitive function. CONCLUSIONS: These results demonstrate that postoperative infiltration of CD8 + T cells into the hippocampus and subsequent secretion of IFN-γ contribute to the inhibition of AHN and cognitive decline later following surgery.

Efficient Ternary Mn-Based Spinel Oxide with Multiple Active Sites for Oxygen Evolution Reaction Discovered via High-Throughput Screening Methods.

The discovery of more efficient and stable catalysts for oxygen evolution reaction (OER) is vital in improving the efficiency of renewable energy generation devices. Given the large numbers of possible binary and ternary metal oxide OER catalysts, high-throughput methods are necessary to accelerate the rate of discovery. Herein, Mn-based spinel oxide, Fe10 Co40 Mn50 O, is identified for the first time using high-throughput methods demonstrating remarkable catalytic activity (overpotential of 310 mV on fluorine-doped tin oxide (FTO) substrate and 237 mV on Ni foam at 10 mA cm-2 ). Using a combination of soft X-ray absorption spectroscopy and electrochemical measurements, the high catalytic activity is attributed to 1) the formation of multiple active sites in different geometric sites, tetrahedral and octahedral sites; and 2) the formation of active oxyhydroxide phase due to the strong interaction of Co2+ and Fe3+ . Structural and surface characterizations after OER show preservation of Fe10 Co40 Mn50 O surface structure highlighting its durability against irreversible redox damage on the catalytic surface. This work demonstrates the use of a high-throughput approach for the rapid identification of a new catalyst, provides a deeper understanding of catalyst design, and addresses the urgent need for a better and stable catalyst to target greener fuel.

Eosinophil extracellular traps in asthma: implications for pathogenesis and therapy.

Asthma is a common, chronic inflammatory disease of the airways that affects millions of people worldwide and is associated with significant healthcare costs. Eosinophils, a type of immune cell, play a critical role in the development and progression of asthma. Eosinophil extracellular traps (EETs) are reticular structures composed of DNA, histones, and granulins that eosinophils form and release into the extracellular space as part of the innate immune response. EETs have a protective effect by limiting the migration of pathogens and antimicrobial activity to a controlled range. However, chronic inflammation can lead to the overproduction of EETs, which can trigger and exacerbate allergic asthma. In this review, we examine the role of EETs in asthma.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia: a case report.

BACKGROUND: Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. CASE PRESENTATION: A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. CONCLUSIONS: This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.