Fertility-sparing surgery in children and adolescents with borderline ovarian tumors: a retrospective study.

OBJECTIVE: To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. METHODS: Patients with BOTs younger than 20 years who underwent FSS were included in this study. RESULTS: A total of 34 patients were included, with a median patient age of 17 (range, 3-19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8-40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10-148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. CONCLUSIONS: Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD). METHODS: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding. RESULTS: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively. CONCLUSIONS: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

The effect of cognitive impairment based on Mini-Mental State Examination (MMSE) on suicidal tendency in patients with schizophrenia: A large cross-sectional study.

BACKGROUND: The effect of cognitive function on suicidal tendency in patients with schizophrenia is still inconclusive. This study aimed to explore the effect of cognitive impairment on suicidal tendency in schizophrenia patients and the risk factors of suicidal tendency in schizophrenia patients with cognitive impairment. METHODS: A total of 988 subjects were recruited for this study and finally 517 patients were included in the statistical analysis. Sociodemographic information was collected for each subject. Mini-Mental State Examination (MMSE) was used to assess patients' cognitive functioning. In addition, the Positive and Negative Syndrome Scale (PANSS) positive subscale, Insomnia Severity Index (ISI), and Beck Scale for Suicide Ideation (BSI) were used to assess psychotic symptoms, severity of insomnia, and intensity of suicidal ideation, respectively. RESULTS: Schizophrenia patients with cognitive dysfunction were significantly less likely to develop suicidal tendencies than those without cognitive dysfunction (P < 0.05, OR = 0.58, 95%CI: 0.39-0.81). In patients with cognitive impairment, those with suicidal tendency had substantially higher scores on BSI, ISI, EC, PD, IRI, F1, and PANSS positive subscale, and took more types of antipsychotic drugs than those without suicidal tendency (all P < 0.05), and the results of binary logistic regression analysis showed that, PANSS positive subscale score (B = 0.06, p = 0.04, OR = 1.07, 95%CI: 1.00-1.13) was a risk factor for suicidal tendencies. CONCLUSIONS: Our findings suggest that schizophrenia patients with cognitive dysfunction are significantly less likely to develop suicidal tendencies. Moreover, positive symptom is a risk factor for suicidal tendencies in schizophrenia patients with cognitive dysfunction.

Sex differences and risk factors of self-reported suicide attempts in middle-aged Chinese Han patients with first-episode drug-naïve anxious depression: a large-scale cross-sectional study.

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

Novel insights into dimethylsulfoniopropionate cleavage by deep subseafloor fungi.

Dimethylsulfoniopropionate (DMSP), a key organic sulfur compound in marine and subseafloor sediments, is degraded by phytoplankton and bacteria, resulting in the release of the climate-active volatile gas dimethylsulfide (DMS). However, it remains unclear if dominant eukaryotic fungi in subseafloor sediments possess specific abilities and metabolic mechanisms for DMSP degradation and DMS formation. Our study provides the first evidence that fungi from coal-bearing sediments ∼2 km below the seafloor, such as Aspergillus spp., Chaetomium globosum, Cladosporium sphaerospermum, and Penicillium funiculosum, can degrade DMSP and produce DMS. In Aspergillus sydowii 29R-4-F02, which exhibited the highest DMSP-dependent DMS production rate (16.95 pmol/µg protein/min), two DMSP lyase genes, dddP and dddW, were identified. Remarkably, the dddW gene, previously observed only in bacteria, was found to be crucial for fungal DMSP cleavage. These findings not only extend the list of fungi capable of degrading DMSP, but also enhance our understanding of DMSP lyase diversity and the role of fungi in DMSP decomposition in subseafloor sedimentary ecosystems.

Transcription of NOD1 and NOD2 and their interaction with CARD9 and RIPK2 in IFN signaling in a perciform fish, the Chinese perch, Siniperca chuatsi.

NOD1 and NOD2 as two representative members of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family play important roles in antimicrobial immunity. However, transcription mechanism of nod1 and nod2 and their signal circle are less understood in teleost fish. In this study, with the cloning of card9 and ripk2 in Chinese perch, the interaction between NOD1, NOD2, and CARD9 and RIPK2 were revealed through coimmunoprecipitation and immunofluorescence assays. The overexpression of NOD1, NOD2, RIPK2 and CARD9 induced significantly the promoter activity of NF-κB, IFNh and IFNc. Furthermore, it was found that nod1 and nod2 were induced by poly(I:C), type I IFNs, RLR and even NOD1/NOD2 themselves through the ISRE site of their proximal promoters. It is thus indicated that nod1 and nod2 can be classified also as ISGs due to the presence of ISRE in their proximal promoter, and their expression can be mechanistically controlled through PRR pathway as well as through IFN signaling in antiviral immune response.

The impact of PET/CT and brain MRI for metastasis detection among patients with clinical T1-category lung cancer: Findings from a large-scale cohort study.

PURPOSE: [18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics. METHODS: The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan-Meier analysis for survival in post-operation patients with and without PET/CT plus MRI. RESULTS: 2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001). CONCLUSION: The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm.

Application of smart hydrogel materials in cartilage injury repair: A systematic review and meta-analysis.

OBJECTIVE: Cartilage injury is a common clinical condition, and treatment approaches have evolved over time from traditional conservative and surgical methods to regenerative repair. In this context, hydrogels, as widely used biomaterials in the field of cartilage repair, have garnered significant attention. Particularly, responsive hydrogels (also known as "smart hydrogels") have shown immense potential due to their ability to respond to various physicochemical properties and environmental changes. This paper aims to review the latest research developments of hydrogels in cartilage repair, utilizing a more systematic and comprehensive meta-analysis approach to evaluate the research status and application value of responsive hydrogels. The goal is to determine whether these materials demonstrate favorable therapeutic effects for subsequent clinical applications, thereby offering improved treatment methods for patients with cartilage injuries. METHOD: This study employed a systematic literature search method to summarize the research progress of responsive hydrogels by retrieving literature on the subject and review studies. The search terms included "hydrogel" and "cartilage," covering data from database inception up to October 2023. The quality of the literature was independently evaluated using Review Manager v5.4 software. Quantifiable data was statistically analyzed using the R language. RESULTS: A total of 7 articles were retrieved for further meta-analysis. In the quality assessment, the studies demonstrated reliability and accuracy. The results of the meta-analysis indicated that responsive hydrogels exhibit unique advantages and effective therapeutic outcomes in the field of cartilage repair. Subgroup analysis revealed potential influences of factors such as different types of hydrogels and animal models on treatment effects. CONCLUSION: Responsive hydrogels show significant therapeutic effects and substantial application potential in the field of cartilage repair. This study provides strong scientific evidence for their further clinical applications and research, with the hope of promoting advancements in the treatment of cartilage injuries.

Diatomite supported highly-dispersed ZnO/Zn-co-embedded ZIF-8 derived porous carbon composites for adsorption desulfurization.

The metal organic framework (MOFs)-derived porous carbon materials with highly dispersed metal active sites were of the exclusive application foreground in many field, such as catalyst, electrochemistry, adsorption desulfurization and so on. However, the loss issue of metal active sites in MOFs frame was indispensable during the high temperature carbonization because of the lower boiling point of many metals, thus fundamentally affecting the atom-scale uniform distribution merit of MOFs-derived porous carbon materials. This work was to provide a novel strategy to address the loss issue of the active metal volatilization in the fabrication of MOFs-derived porous carbon materials. The ZnO nanosheets were pre-grown on the surface of diatomite by using in-situ microwave-assisted preparation, and thereafter the Zn-containing ZIF-8 particles covered the surface of ZnO nanosheets by virtue of the ZnO-induced growth. The results affirmed that the high content Zn-doped porous carbon materials were achieved and the Zn volatilization in MOFs was restrained on account of the occurrence of ZnO on diatomite (DE) surface during the carbonization. The adsorption desulfurization performance of the ZnO/Zn-embedded porous carbon materials/DE (ZnO/Zn/C@DE) was examined by the sulfur-containing compounds in simulated oil. The adsorption desulfurization performance investigation indicated that the ZnO/Zn/C@DE had the optimum adsorption capacities of 45.3 mg/g for benzothiophene and 37.4 mg/g for thiophene. Nonetheless, the competitive adsorption desulfurization finding of toluene in simulated oil showed that the adsorption capacities of ZnO/Zn/C@DE for TH and BT were dramatically descended, suggesting the presence of S-M interaction, wherein S stood for the S atom in a thiophene molecule and their analogs, and M for Zn atoms in porous carbon materials.

Photoinduced Dynamics of a Single-Walled Carbon Nanotube with a sp3 Defect: The Importance of Excitonic Effects.

Herein, we employed linear-response time-dependent functional theory nonadiabatic dynamic simulations to explore the photoinduced exciton dynamics of a chiral single-walled carbon nanotube CNT(6,5) covalently doped with a 4-nitrobenzyl group (CNT65-NO2). The results indicate that the introduction of a sp3 defect leads to the splitting of the degenerate VBM/VBM-1 and CBM/CBM+1 states. Both the VBM upshift and the CBM downshift are responsible for the experimentally observed redshifted E11* trapping state. The simulations reveal that the photoinduced exciton relaxation dynamics completes within 500 fs, which is consistent with the experimental work. On the other hand, we also conducted the nonadiabatic carrier (electron and hole) dynamic simulations, which completely ignore the excitonic effects. The comparison demonstrates that excitonic effects are indispensable. Deep analyses show that such effects induce several dark states, which play an important role in regulating the photoinduced dynamics of CNT65-NO2. The present work demonstrates the importance of including excitonic effects in simulating photoinduced processes of carbon nanotubes. In addition, it not only rationalizes previous experiments but also provides valuable insights that will help in the future rational design of novel covalently doped carbon nanotubes with superior photoluminescent properties.

The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

Flexible Meso Electronics and Photonics Based on Cocoon Silk and Applications.

Flexible electronics, applicable to enlarged health, AI big data medications, etc., have been one of the most important technologies of this century. Due to its particular mechanical properties, biocompatibility, and biodegradability, cocoon silk (or SF, silk fibroin) plays a key role in flexible electronics/photonics. The review begins with an examination of the hierarchical meso network structures of SF materials and introduces the concepts of meso reconstruction, meso doping, and meso hybridization based on the correlation between the structure and performance of silk materials. The SF meso functionalization was developed according to intermolecular nuclear templating. By implementation of the techniques of meso reconstruction and functionalization in the refolding of SF materials, extraordinary performance can be achieved. Relying on this strategy, particularly designed flexible electronic and photonic components can be developed. This review covers the latest ideas and technologies of meso flexible electronics and photonics based on SF materials/meso functionalization. As silk materials are biocompatible and human skin-friendly, SF meso flexible electronic/photonic components can be applied to wearable or implanted devices. These devices are applicable in human physiological signals and activities sensing/monitoring. In the case of human-machine interaction, the devices can be applicable in in-body information transmission, computation, and storage, with the potential for the combination of artificial intelligence and human intelligence.

A novel framework for three-dimensional electrical impedance tomography reconstruction of maize ear via feature reconfiguration and residual networks.

Electrical impedance tomography (EIT) provides an indirect measure of the physiological state and growth of the maize ear by reconstructing the distribution of electrical impedance. However, the two-dimensional (2D) EIT within the electrode plane finds it challenging to comprehensively represent the spatial distribution of conductivity of the intact maize ear, including the husk, kernels, and cob. Therefore, an effective method for 3D conductivity reconstruction is necessary. In practical applications, fluctuations in the contact impedance of the maize ear occur, particularly with the increase in the number of grids and computational workload during the reconstruction of 3D spatial conductivity. These fluctuations may accentuate the ill-conditioning and nonlinearity of the EIT. To address these challenges, we introduce RFNetEIT, a novel computational framework specifically tailored for the absolute imaging of the three-dimensional electrical impedance of maize ear. This strategy transforms the reconstruction of 3D electrical conductivity into a regression process. Initially, a feature map is extracted from measured boundary voltage via a data reconstruction module, thereby enhancing the correlation among different dimensions. Subsequently, a nonlinear mapping model of the 3D spatial distribution of the boundary voltage and conductivity is established, utilizing the residual network. The performance of the proposed framework is assessed through numerical simulation experiments, acrylic model experiments, and maize ear experiments. Our experimental results indicate that our method yields superior reconstruction performance in terms of root-mean-square error (RMSE), correlation coefficient (CC), structural similarity index (SSIM), and inverse problem-solving time (IPST). Furthermore, the reconstruction experiments on maize ears demonstrate that the method can effectively reconstruct the 3D conductivity distribution.

Pluronic F127 hydrogel-loaded extracellular vesicles from adipose-derived mesenchymal stem cells promote tracheal cartilage regeneration via SCNN1B delivery.

Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (AMSC-EVs) have been highlighted as a cell-free therapy due to their regenerative capability to enhance tissue and organ regeneration. Herein, we aimed to examine the mechanism of PF127-hydrogel@AMSC-EVs in promoting tracheal cartilage defect repair. Based on bioinformatics methods, SCNN1B was identified as a key gene for the osteogenic differentiation of AMSCs induced by AMSC-EVs. EVs were isolated from rat AMSCs and then loaded onto thermo-sensitive PF-127 hydrogel to develop PF127-hydrogel@AMSC-EVs. It was established that PF127-hydrogel@AMSC-EVs could effectively deliver SCNN1B into AMSCs, where SCNN1B promoted AMSC osteogenic differentiation. The promotive effect was evidenced by enhanced ALP activity, extracellular matrix mineralization, and expression of s-glycosaminoglycan, RUNX2, OCN, collagen II, PERK, and ATF4. Furthermore, the in vivo experiments revealed that PF127-hydrogel@AMSC-SCNN1B-EVs stimulated tracheal cartilage regeneration in rats through PERK/ATF4 signaling axis activation. Therefore, PF127-hydrogel@AMSC-SCNN1B-EVs may be a novel cell-free biomaterial to facilitate tracheal cartilage regeneration and cartilage injury repair.

[Screw versus Kirschner wire fixation for lateral humeral condyle fractures in children:a meta analysis].

OBJECTIVE: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children. METHODS: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3. RESULTS: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22, 95%CI(0.09, 0.56), P=0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate(P>0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18, 95%CI(0.05, 0.65), P=0.009]. CONCLUSION: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids.

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages' role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

Adipose-derived stem cells derived decellularized extracellular matrix enabled skin regeneration and remodeling.

The tissues or organs derived decellularized extracellular matrix carry immunogenicity and the risk of pathogen transmission, resulting in limited therapeutic effects. The cell derived dECM cultured in vitro can address these potential risks, but its impact on wound remodeling is still unclear. This study aimed to explore the role of decellularized extracellular matrix (dECM) extracted from adipose derived stem cells (ADSCs) in skin regeneration. Methods: ADSCs were extracted from human adipose tissue. Then we cultivated adipose-derived stem cell cells and decellularized ADSC-dECM for freeze-drying. Western blot (WB), enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) were conducted to analyzed the main protein components in ADSC-dECM. The cell counting assay (CCK-8) and scratch assay were used to explore the effects of different concentrations of ADSC-dECM on the proliferation and migration of human keratinocytes cells (HaCaT), human umbilical vein endothelia cells (HUVEC) and human fibroblasts (HFB), respectively. Moreover, we designed a novel ADSC-dECM-CMC patch which used carboxymethylcellulose (CMC) to load with ADSC-dECM; and we further investigated its effect on a mouse full thickness skin wound model. Results: ADSC-dECM was obtained after decellularization of in vitro cultured human ADSCs. Western blot, ELISA and mass spectrometry results showed that ADSC-dECM contained various bioactive molecules, including collagen, elastin, laminin, and various growth factors. CCK-8 and scratch assay showed that ADSC-dECM treatment could significantly promote the proliferation and migration of HaCaT, human umbilical vein endothelia cells, and human fibroblasts, respectively. To evaluate the therapeutic effect on wound healing in vivo, we developed a novel ADSC-dECM-CMC patch and transplanted it into a mouse full-thickness skin wound model. And we found that ADSC-dECM-CMC patch treatment significantly accelerated the wound closure with time. Further histology and immunohistochemistry indicated that ADSC-dECM-CMC patch could promote tissue regeneration, as confirmed via enhanced angiogenesis and high cell proliferative activity. Conclusion: In this study, we developed a novel ADSC-dECM-CMC patch containing multiple bioactive molecules and exhibiting good biocompatibility for skin reconstruction and regeneration. This patch provides a new approach for the use of adipose stem cells in skin tissue engineering.

Structure and dynamics determine G protein coupling specificity at a class A GPCR.

G protein coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR-G protein complexes, little is known about the mechanism of G protein coupling specificity. The ß2-adrenergic receptor is an example of GPCR with high selectivity for Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gαi family of G proteins inhibiting adenylyl cyclase. By developing a new Gαi-biased agonist (LM189), we provide structural and biophysical evidence supporting that distinct conformations at ICL2 and TM6 are required for coupling of the different G protein subtypes Gαs and Gαi. These results deepen our understanding of G protein specificity and bias and can accelerate the design of ligands that select for preferred signaling pathways.

Does the Sagittal Radiographic Morphology of Subtalar Joint Affect the Alignment of Foot?

OBJECTIVES: The etiology of flatfoot and cavus foot is multicausal and controversial. So far, no literature reports the relationship between the sagittal morphology of subtalar joint and the alignment of foot. The purpose of this study was to explore whether the subtalar alignment would influence the configuration of foot. METHODS: From January 2017 to January 2020, we included 109 feet in the flatfoot group, 95 feet in the cavus group, and 104 feet in the control group in this retrospective comparative study. The Gissane angle and calcaneal posterior articular surface inclination angle represented the sagittal morphology of the subtalar joint. Meary's angle, calcaneal pitch angle, and talar pitch angle reflected the alignment of foot. They were measured in the weightbearing foot X-rays. The angles in different groups were compared via Mann-Whitney U test. We calculated the correlation between the sagittal alignment of subtalar joint and the alignment of foot using Spearman's correlation analysis. Interobserver and intraobserver reliability were calculated. RESULTS: The Gissane angle, calcaneal posterior articular surface inclination angle, Meary's angle, talar pitch angle, and calcaneal pitch angle were significantly different in the three groups. The Gissane angle had an excellent correlation with the Meary's angle (r = 0.850, p < 0.0001), and the talar pitch angle (r = -0.825, p < 0.0001), and a good correlation with the calcaneal pitch angle (r = 0.638, p < 0.0001). The calcaneal posterior articular surface inclination angle had an excellent correlation with the Meary's angle (r = -0.902, p < 0.001), and the talar pitch angle (r = 0.887, p < 0.0001), and a good correlation with the calcaneal pitch angle (r = -0.702, p < 0.0001). The interobserver and intraobserver reliability for all radiographic measurements was good to excellent. CONCLUSION: A subtalar joint with a larger Gissane angle and a more horizontal calcaneal posterior articular surface angle tended to have a higher foot arch and vice versa. The inspiration from this study was that the deformities of flatfoot and cavus foot may relate to the subtalar deformity.

Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.