Hydrogel encapsulation facilitates a low-concentration cryoprotectant for cryopreservation of mouse testicular tissue.

Cryopreserved testicular tissue offers a promising method to restore fertility in male infertility patients. Current protocols rely on high concentrations of penetrating cryoprotectants (pCPAs), such as dimethyl sulfoxide (DMSO), which necessitating complex washing procedures and posing risks of toxicity. Hydrogel encapsulation presents a non-toxic alternative for cellular cryopreservation. This study investigates the effects of various types, concentrations, and thicknesses of hydrogel encapsulation on the cryopreservation of mouse testicular tissue. Testicular tissues loaded with varying concentrations of DMSO were encapsulated in alginate or gelatin-methacryloyl (GelMA) hydrogels. We evaluated hydrogels as potential CPAs to reduce pCPA concentrations and determine optimal combinations for cryopreservation. Post-cryopreservation, tissues were cultured using organ culture methods to assess spermatogenesis progression. Cryomicroscopy and differential scanning calorimetry (DSC) were used to examine ice crystal formation, melting enthalpy, and non-freezing water content in different hydrogels during cooling. Results indicate that 3 % alginate or 5 % GelMA hydrogel with thin encapsulation optimally preserves mouse testicular tissue. Using 20 % DMSO in 5 % GelMA thin encapsulation showed comparable apoptosis rates, improved morphology, higher mitochondrial activity, and enhanced antioxidant capacity compared to conventional 30 % DMSO without encapsulation. This suggests that hydrogel encapsulation reduces pCPA concentration by 10 %, thereby mitigating toxic damage. Hydrogel encapsulation can reduce basement membrane shrinkage of testicular tissue during cryopreservation. Moreover, frozen tissues remained viable with preserved germ cells after being cultured for one week on alginate methacryloyl (AlgMA) hydrogel using the gas-liquid interphase method. Cryomicroscopy and DSC studies confirmed the hydrogel's ability to inhibit ice crystal growth. In conclusion, this study introduces novel strategies for male fertility preservation and advances cryopreservation technology for clinical applications in assisted reproduction.

l-Proline and GelMA hydrogel complex：An efficient antifreeze system for cell cryopreservation.

Cryopreservation of biological samples is an important technology for expanding their applications in the biomedical field. However, the quality and functionality of samples after rewarming are limited by the toxicity of commonly used cryoprotectant agents (CPAs). Here, we developed a novel preservation system by combining the natural amino acid l-proline (L-Pro) with gelatin methacryloyl (GelMA) hydrogels. Compared with dimethyl sulfoxide (DMSO), L-Pro and GelMA demonstrated excellent biocompatibility when co-culturing with cells. Cryopreservation procedures were optimized using 3T3 as model cells. The results showed that rapid cooling was the most suitable cooling procedure for L-Pro and GelMA among the three cooling procedures. Co-culturing with cells for 3 h before cryopreservation, 6 % L-Pro +7 % GelMA had the highest survival rate, reaching up to 80 %. Differential Scanning Calorimetry (DSC) analysis showed that 6 % L-Pro + 7 % GelMA lowered the freezing point of the solution to -4.2 °C and increased the unfrozen water content to 20 %. To the best of our knowledge, this is the first report of cell cryopreservation using a combination of L-Pro and GelMA hydrogels, which provides a new strategy for improving cell cryopreservation.

The Global Burden of Gynecological Diseases from 1990 to 2019.

INTRODUCTION: Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to estimate the disease burden of gynecological diseases and describe their trends in women of all ages from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), authors examined the incidence, disability-adjusted life years, and deaths from gynecological diseases by age in 204 countries and territories worldwide from 1990 to 2019. Analyses were conducted in 2022. RESULTS: Globally, the age-standardized incidence rate and age-standardized disability-adjusted life year rate (ASDR) of gynecological diseases decreased by -0.176% and -0.245%, respectively from 1990 to 2019. Low socioeconomic development index countries had the highest age-standardized incidence rate and ASDR in 2019. The age-specific incidence rate of gynecological diseases in women aged 15-29 years increased from 1990 to 2019, and the 20-24-year age group increased the greatest by 0.21%. Polycystic ovary syndrome and other types of benign disorders contributed to the major increase. CONCLUSIONS: Although the disease burden of gynecological diseases decreased slightly between 1990 and 2019 globally, it remained highest in low socioeconomic development index countries. The disease burden in 20-24-year age group exhibited the fastest growth, with polycystic ovary syndrome and other types of benign disorders playing a significant role. Urgent and effective measures should be taken to target different age groups, types of gynecological disease, and regions with high disease burdens.

Cardiovascular MRI Reference Ranges for Heart, Aorta, and Pulmonary Artery in Healthy Chinese Children.

BACKGROUND: Cardiovascular magnetic resonance (cardiac MR) reference ranges in Chinese children are lacking. PURPOSE: To establish age- and sex-specific reference ranges for cardiac MR parameters in a cohort of healthy Chinese children. STUDY TYPE: Retrospective. SUBJECTS: One hundred ninety-six healthy children (mean age 9.5 ± 3.6 years, 111 boys). FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession. ASSESSMENT: Biventricular volume and ejection fractions (EF), left atrial (LA) volume, right atrial (RA) area, left ventricular (LV) mass and thickness, aortic root (AR), and main pulmonary artery (MPA) dimensions were measured. Parameters were compared between age groups and sex. The relationships between parameters and age, body mass index (BMI) and body surface area (BSA) were investigated. STATISTICAL TESTS: Independent-samples t tests; Pearson's correlation. A P value <0.05 was considered statistically significant. RESULTS: Generally, boys exhibited greater absolute measurements of LV volume (end-diastolic: 94.4 ± 29.5 vs. 81.3 ± 31.0 mL), LA volume (end-diastolic: 42.6 ± 13.4 vs. 38.0 ± 13.3 mL), RA area (end-diastolic: 11.6 ± 2.5 vs. 10.8 ± 2.6 cm2), LV thickness (base: 4.4 ± 1.1 vs. 3.8 ± 0.9 mm), AR dimensions (annuls: 16.3 ± 2.7 vs. 15.0 ± 2.8 mm), and MPA dimensions (14.3 ± 2.3 vs. 13.1 ± 2.4 mm) than girls did. However, these differences were not observed when the measurements were normalized to BSA (LV volume: 75.3 ± 11.7 vs. 71.9 ± 12.3 mL/m2, P = 0.052; LA volume: 34.8 ± 8.9 vs. 34.5 ± 7.6 mL/m2, P = 0.783; RA area: 9.7 ± 2.3 vs. 10.2 ± 2.3 cm2/m2, P = 0.107; LV thickness: 3.6 ± 0.7 vs. 3.6 ± 0.9 mm/m2, P = 0.990; AR: 13.6 ± 2.7 vs. 14.3 ± 3.4 mm/m2, P = 0.108; MPA: 11.9 ± 2.3 vs. 12.4 ± 2.4 mm/m2, P = 0.118). Boys had greater RV volume (end-diastolic: 98.7 ± 33.5 vs. 82.7 ± 33.1 mL) and LV mass (52.6 ± 20.2 vs. 41.4 ± 16.0 g) compared to girls, irrespective of whether the values were indexed or not for BSA. Additionally, there were significant associations between age, BMI, and BSA with biventricular volume, LA volume, RA area, LV mass and thickness, AR and MPA dimensions in both boys and girls. DATA CONCLUSION: This study suggests reference ranges at 1.5 T for Chinese children. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Learning to Sketch: A Neural Approach to Item Frequency Estimation in Streaming Data.

Recently, there has been a trend of designing neural data structures to go beyond handcrafted data structures by leveraging patterns of data distributions for better accuracy and adaptivity. Sketches are widely used data structures in real-time web analysis, network monitoring, and self-driving to estimate item frequencies of data streams within limited space. However, existing sketches have not fully exploited the patterns of the data stream distributions, making it challenging to tightly couple them with neural networks that excel at memorizing pattern information. Starting from the premise, we envision a pure neural data structure as a base sketch, which we term the meta-sketch, to reinvent the base structure of conventional sketches. The meta-sketch learns basic sketching abilities from meta-tasks constituted with synthetic datasets following Zipf distributions in the pre-training phase and can be quickly adapted to real (skewed) distributions in the adaption phase. The meta-sketch not only surpasses its competitors in sketching conventional data streams but also holds good potential in supporting more complex streaming data, such as multimedia and graph stream scenarios. Extensive experiments demonstrate the superiority of the meta-sketch and offer insights into its working mechanism.

Adipose-derived stem cell exosomes promote tumor characterization and immunosuppressive microenvironment in breast cancer.

Adipose-derived stem cells (ASC) or autologous fat transplantation could be used to ameliorate breast cancer postoperative deformities. This study aims to explore the action of ASC and ASC-exosomes (ASC-exos) in breast cancer characterization and tumor microenvironment immunity, which provided a new method into the application of ASC-exos. ASC were extracted from human adipose tissue for the isolation and verification of ASC-exos. ASC-exos were co-cultured with CD4+T cells, CD14+ monocytes and MCF-7 cells, respectively. The tumor formation of nude mice was also constructed. Cell characterization was determined by CCK8, scratch assay, and Transwell. Hematoxylin-eosin (HE), immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to observe the histopathology and protein expression. CD4+T cell and CD14+ monocytes differentiation was detected by flow cytometry. Western blot, qRT-PCR and RNAseq were used to detect the action of ASC-exos on gene and protein expression. CD4+T cells could take up ASC-exos. ASC-exos inhibited Th1 and Th17 differentiation and promoted Treg differentiation of CD4+T cells. ASC-exos inhibited M1 differentiation and promoted M2 differentiation of CD14+ monocytes. ASC-exos promoted the migration, proliferation, and invasion, while inhibited apoptosis of MCF-7 cells. ASC-exos promoted the tumor formation of breast cancer. The effect of ASC-exos on tumor microenvironment immunity was in accordance with the above in vitro results. TOX, CD4 and LYZ1 genes were upregulated, while Mettl7b and Serpinb2 genes were downregulated in ASC-exos group. Human T-cell leukemia virus 1 infection pathway was significantly enriched in ASC-exos. Thus, ASC-exos promoted breast cancer characterization and tumor microenvironment immunosuppression by regulating macrophage and T cell differentiation.

A retrospective study analyzing if lymph node ratio carbon nanoparticles predict stage III rectal cancer recurrence.

Background: Lymph node ratio has garnered increasing attention as a prognostic marker for rectal cancer; however, few studies have investigated the relationship between lymph node ratio and rectal cancer recurrence. Additionally, Carbon Nanoparticle tracking is a safe and effective strategy for locating tumors and tracking lymph nodes. However, no studies have reported the relationship between Carbon Nanoparticles and rectal cancer recurrence. Methods: Patients with stage III rectal cancer who underwent radical resection between January 2016 and 2020 were analyzed. The primary outcome was tumor recurrence. 269 patients with stage III rectal cancer were included in this study. The effects of lymph node ratio, Carbon Nanoparticles, and other clinicopathological factors on rectal cancer recurrence were assessed using univariate, multivariate analyses and the t-test. Results: Univariate analysis determined tumor recurrence using cytokeratin 19 fragment, CA-199, CEA, N-stage, positive lymph nodes, total lymph nodes, and lymph node ratio(positive/total); with the lymph node ratio being the most relevant. Receiver operating characteristic (ROC) analysis determined lymph node ratio =0.38 as the optimal cutoff value. The analysis of lymph node ratio ≥0.38 and <0.38 showed statistical differences in three indicators: tumor recurrence, CEA, and use of Carbon Nanoparticles. Conclusion: Lymph node ratio is a strong predictor of stage III rectal cancer recurrence and may be considered for inclusion in future tumor-node-metastasis staging and stage III rectal cancer stratification. In addition, we found that Carbon Nanoparticles use significantly increased total lymph nodes and decreased lymph node ratio.

Update on suspensory suture techniques in reconstructive periodontal surgeries.

PURPOSE: Reconstructive periodontal surgery, which has received more and more interest in modern periodontology, can help save severely compromised teeth and solve aesthetic problems caused by the destruction of periodontal tissues in periodontal diseases. Unfortunately, there is few literatures reviewing the use of suspensory suture techniques in reconstructive periodontal surgeries. METHODS: An electronic search of the PubMed and Web of Science was performed. Full-text articles were obtained from the records after screening in the title and abstracts. RESULTS: Effective suture is of central importance to a successful treatment outcome of periodontal surgeries, especially incremental soft or hard tissue surgeries. Limitations in suture techniques may negatively affect the intimate contact of the affected tissues, wound closure and stabilization, and successful wound healing. Suitable anchors can be selected to help achieve this objective. Suspensory sutures may be more precise suture techniques, due to the use of relatively immobile anchors. CONCLUSION: This review aims to provide key points of successful wound healing and summarize the current state of the suspensory suture techniques for reconstructive periodontal surgeries in daily practice, including their treatment application, detailed steps, advantages, and disadvantages.

Quantifying left ventricular myocardial strain in patients with different CAD-RADS levels based on computed tomography feature tracking technology.

To evaluate myocardial strain in patients with different coronary artery disease-reporting and data system (CAD-RADS) levels using the computed tomography (CT) feature tracking technology and to investigate the relationship of myocardial strain with coronary artery calcium scores (CACs) and the degree of coronary artery stenosis. We prospectively enrolled 237 consecutive patients to undergo coronary CT angiography. The participants were divided into the following groups: control (n = 87), CAD-RADS 1 (n = 43), CAD-RADS 2 (n = 43), CAD-RADS 3 (n = 38), and CAD-RADS 4 and above (n = 26). Myocardial strains were analyzed by commercial software, and CACs and coronary stenosis were assessed on post-processing stations. Differences between multiple groups were analyzed using one-way analysis of variance or the Kruskal-Wallis test. Logistic regression were used to analyze the effects of dichotomous variables. As the CAD-RADS level increased, the global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) of the left ventricle based on CT gradually decreased. A significant correlation was observed between global myocardial strain and CACs (GRS: r = - 0.219, GCS: r = 0.189, GLS: r = 0.491; P < 0.05). The independent predictors of obstructive CAD were age (ß = 0.065, odds ratio [OR] = 1.067, P = 0.005), left ventricular ejection fraction (ß = 0.145, OR = 1.156, P = 0.047), and GLS (ß = 0.232, OR = 1.261, P = 0.01). CT-derived GLS of the left ventricle is correlated with CAD-RADS levels and CACs. It may be a better indicator than CACs to reflect the severity of CAD.

How to Keep the Balance between Red and Processed Meat Intake and Physical Activity Regarding Mortality: A Dose-Response Meta-Analysis.

BACKGROUND: Non-communicable diseases have become a major threat to public health, with cardiovascular diseases (CVDs) and cancer being the top two causes of death each year. OBJECTIVE: Our objective is to evaluate the balanced association between the effect of red and processed meat intake on the risk of death and the effect of physical activity on the risk of mortality, where the risk of death includes all causes, CVDs, and cancers. METHODS: We searched electronic databases, including PubMed, ISI Web of Science, Embase, and the Cochrane Library, for prospective studies reporting risk estimates for the association between the intake of red and processed meat, walking, and muscle-strengthening activity (MSA) and the risk of mortality from all causes, CVDs, and cancer. We extracted fully adjusted effect estimates from original studies and performed a summary analysis using the fixed and random-effect models. RESULTS: A conventional meta-analysis showed that red meat and processed meat were positively associated with the risk of mortality, and daily steps and MSA were negatively associated with the risk of death. Further analysis of the dose-response relationship showed that a risk reduction (20%) from 39.5 min/week of MSA or 4100 steps/d was equivalent to an increased risk of all-cause mortality from a daily intake of 103.4 g/d of red meat or 50 g/d of processed meat. The risk was further decreased as the number of steps per day increased, but the risk reversed when the MSA exceeded the threshold (39.5 min/week). CONCLUSIONS: Adherence to physical activity is an effective way to reduce the risk of mortality due to meat intake. However, the total intake of red meat and processed meat should be controlled, especially the latter. Walking is recommended as the main daily physical activity of choice, while MSAs are preferred when time is limited, but it should be noted that longer MSAs do not provide additional benefits.

Multimodality imaging assessment of primary pericardial rhabdomyosarcoma: a case report.

Primary pericardial sarcomas are rare and lethal diseases. To date, only a few cases of primary pericardial sarcomas, such as rhabdomyosarcoma (RMS), have been reported. Since the unusual location of RMS in the pericardium makes it challenging to diagnose, precise diagnostic procedures are required. In this study, we present the case of a 23-year-old man who experienced postprandial obstruction and atypical precordial pain that lasted for a week. Echocardiography revealed a heterogeneous isoechoic pericardial mass with a significant pericardial effusion. Contrast-enhanced CT revealed a massive pericardial effusion along with an irregular, defined, heterogeneously enhancing mass that was located between the pericardium and diaphragm. PET-CT imaging showed an intense FDG uptake in the pericardial mass. Furthermore, cardiac MRI demonstrated malignant characteristics of the pericardial mass and provided a detailed visualization of its exact anatomical connection with both cardiac and extracardiac structures. Finally, a pathologic examination of a puncture biopsy specimen confirmed the diagnosis of primary pericardial RMS. Our case emphasizes the importance of multimodal imaging for the differential diagnosis and evaluation of cardiac involvement, while providing clinicians with crucial information for clinical treatment and decision-making.

Pathologic complete response to TNT + camrelizumab for rectal cancer with surgical anus-preservation: case report and literature review.

Background: This case report demonstrates the efficacy of total neoadjuvant therapy (TNT) based on pathological complete response (PCR). We also discuss the surgical approach to preserving the anus and its perioperative management. Case presentaion: The patient was a 26-year-old woman, with blood in the stool and stool thinning for over two months. Preoperative examination revealed locally advanced rectal cancer invading the left anal raphe and enlarged lymph nodes adjacent to the left internal iliac vessels. The lesion was preoperatively classified as T4bN1bM0 IIIC. Considering the size and depth of the tumor, it was difficult to have sufficient margins for radical resection, and the tumor was too close to the anal orifice. Considering the patient's youth and strong desire to preserve the anus, it was decided to use TNT combined with a camrelizumab regimen. After the entire course of neoadjuvant radiotherapy, the tumor size significantly reduced in fibrotic manifestations, and no enlargement of the lymph nodes adjacent to the left internal iliac vessels was observed. She underwent robotic laparoscopic ultra-low anterior rectal resection, left lateral lymph node dissection, and temporary ileostomy, and no significant residue was observed after all bowel tubes were taken for examination, nor was there cancerous involvement at the distal or radial cut edges, or metastasis. The patient was discharged nine days postoperatively, and no major complications were detected. Follow-up was performed without adjuvant chemotherapy. Conclusions: TNT may be a better surgical option for preserving the anus and for complete radical resection in patients with LARC for whom Miles' resection is indicated.

A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality.

The associations between social isolation, loneliness and the risk of mortality from all causes, cardiovascular disease (CVD) and cancer are controversial. We systematically reviewed prospective studies on the association between social isolation, loneliness and mortality outcomes in adults aged 18 years or older, as well as studies on these relationships in individuals with CVD or cancer, and conducted a meta-analysis. The study protocol was registered with PROSPERO (reg. no. CRD42022299959). A total of 90 prospective cohort studies including 2,205,199 individuals were included. Here we show that, in the general population, both social isolation and loneliness were significantly associated with an increased risk of all-cause mortality (pooled effect size for social isolation, 1.32; 95% confidence interval (CI), 1.26 to 1.39; P < 0.001; pooled effect size for loneliness, 1.14; 95% CI, 1.08 to 1.20; P < 0.001) and cancer mortality (pooled effect size for social isolation, 1.24; 95% CI, 1.19 to 1.28; P < 0.001; pooled effect size for loneliness, 1.09; 95% CI, 1.01 to 1.17; P = 0.030). Social isolation also increased the risk of CVD mortality (1.34; 95% CI, 1.25 to 1.44; P < 0.001). There was an increased risk of all-cause mortality in socially isolated individuals with CVD (1.28; 95% CI, 1.10 to 1.48; P = 0.001) or breast cancer (1.51; 95% CI, 1.34 to 1.70; P < 0.001), and individuals with breast cancer had a higher cancer-specific mortality owing to social isolation (1.33; 95% CI, 1.02 to 1.75; P = 0.038). Greater focus on social isolation and loneliness may help improve people's well-being and mortality risk.

METTL3-mediated m6A modification of lnc KCNQ1OT1 promotes doxorubicin resistance in breast cancer by regulating miR-103a-3p/MDR1 axis.

Doxorubicin (DOX) resistance in breast cancer (BC) poses a huge challenge for the therapeutic effect on BC. Lnc KCNQ1OT1 play crucial roles in chemotherapy resistance. However, the role and mechanism of lnc KCNQ1OT1 in DOX resistance BC have not been investigated, which merits further exploration. Based on MCF-7 and MDA-MB-231 cells, MCF-7/DOX and MDA-MB-231/DOX cells were established using gradient concentrations of DOX. IC50 values and cell viability were determined using MTT. Cell proliferation was investigated by colony formation. Flow cytometry was performed to examine cell apoptosis and cell cycle. Gene expression was examined using qRT-PCR and western blot. The interactions among METTL3, lnc KCNQ1OT1, miR-103a-3p, and MDR1 were validated with MeRIP-qPCR, RIP, and dual-luciferase reporter gene assays. The results showed that Lnc KCNQ1OT1 was highly expressed in DOX-resistant BC cells, and lnc KCNQ1OT1 depletion could enhance DOX sensitivity in BC cells and DOX-resistant BC cells. Besides, lnc KCNQ1OT1 was modulated by MELLT3 in the manner of m6A modification. MiR-103a-3p could interact with lnc KCNQ1OT1 and MDR1. Overexpression of MDR1 abolished the impacts of lnc KCNQ1OT1 depletion on DOX resistance in BC. In conclusion, our results unveiled that in BC cells and DOX-resistant BC cells, lnc KCNQ1OT1 could be mediated by METTL3 through m6A modification to elevate and stabilize its expression, further inhibiting miR-103a-3p/MDR1 axis to promote DOX resistance, which might provide novel thought to overcome DOX resistance in BC.

Financial inclusion role on energy efficiency financing gaps in COVID-19 period: empirical outcomes of emerging nations.

The structural imposed crises of the COVID-19 have halted the system of financial intermediation at large. By this, the energy sector needs huge financing for energy efficiency maximization in the COVID-19 crises. Thus, the current research aims to inquire the role of financial inclusion in filling the energy efficiency financing gaps for the period of COVID-19 outbreak. The governments of many countries are facing fiscal deficits and trying to survive under tight substantial fiscal limitations. So providing a cheap and efficient energy in modern times, under COVID-19 crises, is merely impossible for many economies because the main source of income for energy sector is the energy users, and having inefficient energy for consumption is raising energy poverty at large. Therefore, COVID-19 crises raised a wide energy financing gap in modern times that needs a fix. However, this research is suggesting the system to make financial inclusion structure as effective, to fill the energy financing gap, for post-COVID-19 time, and to develop a viable and sustainable financing option for energy sector in long-run perspective. This study also validated the empirical role of financial inclusion on energy poverty and energy efficiency, with historical data, to justify the significance of financial inclusion for energy financing gap fulfillment. More so, this paper is also recommending new policy implications for the stakeholders to utilize. We believe if the recommended policy recommendations are considered for practice, the energy financing gap in post-COVID-19 era would be mitigated, and there is a high probability to supply the efficient energy to the end users.