Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

RETRACTED: Cheng et al. Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test. Genes 2021, 12, 1539.

The Genes journal retracts the article "Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test" [...].

Aberrant Expression of SLC7A11 Impairs the Antimicrobial Activities of Macrophages in Staphylococcus Aureus Osteomyelitis in Mice.

Staphylococcus aureus (S. aureus) persistence in macrophages, potentially a reservoir for recurrence of chronic osteomyelitis, contributes to resistance and failure in treatment. As the mechanisms underlying survival of S. aureus in macrophages remain largely unknown, there has been no treatment approved. Here, in a mouse model of S. aureus osteomyelitis, we identified significantly up-regulated expression of SLC7A11 in both transcriptomes and translatomes of CD11b+F4/80+ macrophages, and validated a predominant distribution of SLC7A11 in F4/80+ cells around the S. aureus abscess. Importantly, pharmacological inhibition or genetic knockout of SLC7A11 promoted the bactericidal function of macrophages, reduced bacterial burden in the bone and improved bone structure in mice with S. aureus osteomyelitis. Mechanistically, aberrantly expressed SLC7A11 down-regulated the level of intracellular ROS and reduced lipid peroxidation, contributing to the impaired bactericidal function of macrophages. Interestingly, blocking SLC7A11 further activated expression of PD-L1 via the ROS-NF-κB axis, and a combination therapy of targeting both SLC7A11 and PD-L1 significantly enhanced the efficacy of clearing S. aureus in vitro and in vivo. Our findings suggest that targeting both SLC7A11 and PD-L1 is a promising therapeutic approach to reprogram the bactericidal function of macrophages and promote bacterial clearance in S. aureus osteomyelitis.

Early Therapeutic Drug Monitoring Optimizes Teicoplanin Use in Febrile Neutropenic Patients with Hematological Malignancies.

INTRODUCTION: A target trough concentration (Cmin) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. METHODS: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. RESULTS: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018). CONCLUSIONS: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.

Engineering CD3/CD137 dual specificity into a DLL3-targeted T-cell engager enhances T-cell infiltration and efficacy against small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICIs) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all SCLC patients are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific). The CD3/CD137 dual-specific Fab was generated to competitively bind to CD3 and CD137 to prevent DLL3-independent cross-linking of CD3 and CD137, which could lead to systemic T-cell activation. We demonstrated that DLL3 trispecific induced better tumor growth control and a marked increase in the number of intratumoral T cells compared to a conventional DLL3-targeted bispecific T-cell engager. These findings suggest that DLL3 trispecific can exert potent efficacy by inducing concurrent CD137 costimulation and provide a promising therapeutic option for SCLC.

Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all patients with SCLC are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific). The CD3/CD137 dual-specific Fab was generated to competitively bind to CD3 and CD137 to prevent DLL3-independent cross-linking of CD3 and CD137, which could lead to systemic T-cell activation. We demonstrated that DLL3 trispecific induced better tumor growth control and a marked increase in the number of intratumoral T cells compared with a conventional DLL3-targeted bispecific T-cell engager. These findings suggest that DLL3 trispecific can exert potent efficacy by inducing concurrent CD137 costimulation and provide a promising therapeutic option for SCLC.

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Association between sex hormones and bone age in boys aged 9-18 years from China.

This study aimed to analyse the association between sex hormones and bone age (BA) in boys aged 9-18 years, both individually and interactively, and further to explore whether nutritional status may influence this association. A retrospective analysis was performed among 1382 Chinese boys with physical measurements, sexual characteristics, BA radiographs and sex hormone indicators from February 2015 to February 2022. A total of 470 (34.0%) boys had advanced BA. BA was positively associated with estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in both advanced and normal BA groups after adjusting for age, genetic height and body mass index. Multiple logistic regression showed that after adjusting for covariates, estradiol (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.14-2.12), LH (OR = 1.43, 95% CI: 1.04-1.96), and testosterone (OR = 1.58, 95% CI: 1.17-2.13) were significantly associated with the increased risk of advanced BA in boys, and the association was reinforced when these hormones were interactively explored. Stratified by nutritional status, the interaction between estradiol, LH, and testosterone showed a strong association with advanced BA in boys with normal weight.

Trends in survival of ovarian clear cell carcinoma patients from 2000 to 2015.

Purpose: To analyze changes in survival outcomes in patients with ovarian clear cell carcinoma (OCCC) treated consecutively over a 16-year period using a population-based cohort. Methods: We conducted a retrospective analysis of OCCC from 2000 to 2015 using data from the Surveillance, Epidemiology, and End Results (SEER) program. The ovarian cancer-specific survival (OCSS) and overall survival (OS) were analyzed according to the year of diagnosis. Joinpoint Regression Program, Kaplan-Meier analysis, and multivariate Cox regression analyses were used for statistical analysis. Results: We included 4257 patients in the analysis. The analysis of annual percentage change in OCSS (P=0.014) and OS (P=0.006) showed that patients diagnosed in later years had significantly better outcomes compared to those diagnosed in early years. The results of the multivariate Cox regression analyses showed that the year of diagnosis was the independent prognostic factor associated with OCSS (P=0.004) and had a borderline effect on OS (P=0.060). Regarding the SEER staging, the OCSS (P=0.017) and OS (P=0.004) of patients with distant stage showed a significant trend toward increased, while no significant trends were found in the survival of patients with localized or regional stage diseases. Similar trends were found in those aged <65 years or those treated with surgery and chemotherapy. However, no statistically significant changes in the survival rate were found in those aged ≥65 years or those receiving surgery alone regardless of SEER stage during the study period. Conclusions: Our study observed a significant increase in the survival outcomes in OCCC from 2000 to 2015, and patients aged <65 years and those with distant stage experienced a greater improvement in survival.

Aberrant activated Notch1 promotes prostate enlargement driven by androgen signaling via disrupting mitochondrial function in mouse.

The prostate is a vital accessory gonad in the mammalian male reproductive system. With the ever-increasing proportion of the population over 60 years of age worldwide, the incidence of prostate diseases, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), is on the rise and is gradually becoming a significant medical problem globally. The notch signaling pathway is essential in regulating prostate early development. However, the potential regulatory mechanism of Notch signaling in prostatic enlargement and hyperplasia remains unclear. In this study, we proved that overactivation of Notch1 signaling in mouse prostatic epithelial cells (OEx) led to prostatic enlargement via enhancing proliferation and inhibiting apoptosis of prostatic epithelial cells. Further study showed that N1ICD/RBPJ directly up-regulated the androgen receptor (AR) and enhanced prostatic sensitivity to androgens. Hyper-proliferation was not found in orchidectomized OEx mice without androgen supply but was observed after Dihydrotestosterone (DHT) supplementation. Our data showed that the number of mitochondrion in prostatic epithelial cells of OEx mice was increased, but the mitochondrial function was impaired, and the essential activity of the mitochondrial respiratory electron transport chain was significantly weakened. Disordered mitochondrial number and metabolic function further resulted in excessive accumulation of reactive oxygen species (ROS). Importantly, anti-oxidant N-Acetyl-L-Cysteine (NAC) therapy could alleviate prostatic hyperplasia caused by the over-activation of Notch1 signaling. Furthermore, we observed the incremental Notch signaling activity in progenitor-like club cells in the scRNA-seq data set of human BPH patients. Moreover, the increased number of TROP2+ progenitors and Club cells was also confirmed in our OEx mice. In conclusion, our study revealed that over-activated Notch1 signaling induces prostatic enlargement by increasing androgen receptor sensitivity, disrupting cellular mitochondrial metabolism, increasing ROS, and a higher number of progenitor cells, all of which can be effectively rescued by NAC treatment.

Nickel-Catalyzed Atroposelective C-H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands.

The catalytic asymmetric construction of axially chiral C-N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, and precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C-H alkylation for the construction of C-N axially chiral compounds with the aid of a chiral heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni-Al bimetallic catalyst. A wide range of alkenes, including terminal and internal alkenes, were well compatible with the reaction, providing a variety of benzimidazole derivatives in high yields and enantioselectivities (up to 97:3 e.r.). The key to success was the identification of novel HASPOs as highly effective chiral preligands. Mechanistic studies revealed the catalyst mode of action, and in-depth data science analysis elucidated the key features of the responsible chiral preligands in controlling the enantioselectivity.

Non-lethal exposure to short-wavelength light-emitting diodes modulates tight-junction structure in human corneal epithelial cells via cAMP-dependent signaling.

Light-emitting diodes (LED)-derived lights have been widely used as a medical treatment in photobiomodulation (PBM). However, the PBM effects in ophthalmology are less well investigated. Herein, we explored the effect of LED-generated light on the tight-junction (TJ) formation in human corneal epithelial cells (HCEs). The HCEs were separately exposed to monochromatic LEDs at wavelengths of 365 nm (UVA), 420 nm (violet), 470 nm (blue), 530 nm (green), 590 nm (amber), 660 nm (deep red), and 740 nm (far red) at 10 J/cm2/day for 1 and 2 days. Long-term cultivation of HCEs without LED exposure for up to 14 days was established as a control. The effects of both LED wavelength and culture duration on cell morphology, cAMP-regulated proteins, TJ-associated proteins, and cell growth-associated proteins were also analyzed. Together with the increase in cell number during prolonged cultivation, cAMP, ZO-1, ZO-2, CLDN1, and CLDN4 all increased significantly during long-term cultivation without LED exposure. There was no difference in HCE viability after exposure to all monochromatic LEDs at an accumulated dose of 20 J/cm2. As determined by immunoblotting, UVA, violet, and blue light increased intracellular cAMP, ZO-1, ZO-2, CLDN1, and CLDN4 expression, respectively. UVA and violet, but not blue, light increased PKAreg-pS77 expression. However, none of the other treatments changed the expression of PKAcat-pT197, VASP-pS157, Bax, Bcl-2, or Bcl-xL. Immunofluorescence staining confirmed the formation of TJ structures. The expressions of ZO-1, ZO-2, CLDN1, and CLDN4 as well as TJ structures 2 days following UVA, violet, and blue exposure were similar to those of control cells after 9 days of cultivation. We conclude that short-wavelength LEDs at non-lethal exposure intensities accelerated the formation of TJ structure in HCEs via a cAMP-dependent regulatory cascade.

Pathogenomics for accurate diagnosis, treatment, prognosis of oncology: a cutting edge overview.

The capability to gather heterogeneous data, alongside the increasing power of artificial intelligence to examine it, leading a revolution in harnessing multimodal data in the life sciences. However, most approaches are limited to unimodal data, leaving integrated approaches across modalities relatively underdeveloped in computational pathology. Pathogenomics, as an invasive method to integrate advanced molecular diagnostics from genomic data, morphological information from histopathological imaging, and codified clinical data enable the discovery of new multimodal cancer biomarkers to propel the field of precision oncology in the coming decade. In this perspective, we offer our opinions on synthesizing complementary modalities of data with emerging multimodal artificial intelligence methods in pathogenomics. It includes correlation between the pathological and genomic profile of cancer, fusion of histology, and genomics profile of cancer. We also present challenges, opportunities, and avenues for future work.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation.

Ex vivo patient-derived tumor slices (PDTS) are currently limited by short-term viability in culture. Here, we show how bioengineered hydrogels enable the identification of key matrix parameters that significantly enhance PDTS viability compared to conventional culture systems. As demonstrated using single-cell RNA sequencing and high-dimensional flow cytometry, hydrogel-embedded PDTS tightly preserved cancer, cancer-associated fibroblast, and various immune cell populations and subpopulations in the corresponding original tumor. Cell-cell communication networks within the tumor microenvironment, including immune checkpoint ligand-receptor interactions, were also maintained. Remarkably, our results from a co-clinical trial suggest hydrogel-embedded PDTS may predict sensitivity to immune checkpoint inhibitors (ICIs) in head and neck cancer patients. Further, we show how these longer term-cultured tumor explants uniquely enable the sampling and detection of temporal evolution in molecular readouts when treated with ICIs. By preserving the compositional heterogeneity and complexity of patient tumors, hydrogel-embedded PDTS provide a valuable tool to facilitate experiments targeting the tumor microenvironment.

Dietary intake of low-income adults in South Africa: ultra-processed food consumption a cause for concern.

OBJECTIVE: Given the rapidly changing food environment and proliferation of ultra-processed foods (UPF) in South Africa (SA), this study aimed to critically evaluate dietary quality and adequacy of low-income adults using the Nova classification system and WHO and World Cancer Research Fund dietary guidelines. DESIGN: Secondary household data and 1-d 24-h recalls were analysed from two cross-sectional studies conducted in 2017-2018. Foods consumed were classified according to the Nova classification system. Compliance with WHO dietary guidelines and UPF consumption trends were evaluated. SETTING: Three low-income areas (Langa, Khayalitsha and Mount Frere) in SA were included. PARTICIPANTS: In total, 2521 participants (18-50 years) were included in the study. RESULTS: Participants had a mean energy intake of 7762 kJ/d. Most participants were within the acceptable WHO guideline range for saturated fat (80·4 %), total fat (68·1 %), Na (72·7 %) and free sugar (57·3 %). UPF comprised 39·4 % of diets among the average adult participant. Only 7·0 % of all participants met the WHO guideline for fruit and vegetables and 18·8 % met the guideline for fibre. Those within the highest quartile of share of energy from UPF consumed statistically higher amounts of dietary components to limit and were the highest energy consumers overall. CONCLUSIONS: Low-income adults living in SA are consuming insufficient protective dietary components, while UPF consumption is prevalent. Higher UPF consumers consume larger amounts of nutrients linked to increased chronic disease risk. Policy measures are urgently needed in SA to protect against the proliferation of harmful UPF and to promote and enable consumption of whole and less UPF.

High-resolution full-field optical coherence tomography microscope for the evaluation of freshly excised skin specimens during Mohs surgery: A feasibility study.

Histopathology for tumor margin assessment is time-consuming and expensive. High-resolution full-field optical coherence tomography (FF-OCT) images fresh tissues rapidly at cellular resolution and potentially facilitates evaluation. Here, we define FF-OCT features of normal and neoplastic skin lesions in fresh ex vivo tissues and assess its diagnostic accuracy for malignancies. For this, normal and neoplastic tissues were obtained from Mohs surgery, imaged using FF-OCT, and their features were described. Two expert OCT readers conducted a blinded analysis to evaluate their diagnostic accuracies, using histopathology as the ground truth. A convolutional neural network was built to distinguish and outline normal structures and tumors. Of the 113 tissues imaged, 95 (84%) had a tumor (75 basal cell carcinomas [BCCs] and 17 squamous cell carcinomas [SCCs]). The average reader diagnostic accuracy was 88.1%, with a sensitivity of 93.7%, and a specificity of 58.3%. The artificial intelligence (AI) model achieved a diagnostic accuracy of 87.6 ± 5.9%, sensitivity of 93.2 ± 2.1%, and specificity of 81.2 ± 9.2%. A mean intersection-over-union of 60.3 ± 10.1% was achieved when delineating the nodular BCC from normal structures. Limitation of the study was the small sample size for all tumors, especially SCCs. However, based on our preliminary results, we envision FF-OCT to rapidly image fresh tissues, facilitating surgical margin assessment. AI algorithms can aid in automated tumor detection, enabling widespread adoption of this technique.

Near-Infrared Fluorescence Imaging of miRNA Using a Transmembrane Polypeptide-Based Genetic Reporter.

MicroRNAs (miRNAs) are small noncoding RNAs that play important regulatory roles in multiple biological processes. Many miRNAs exhibit unique expression patterns and are considered as theranostic biomarkers in a variety of human diseases. A reporter system that is capable of imaging miRNA in vivo is crucial for investigating miRNA biology. In the present study, an organic anion-transporting polypeptide 1B3 (OATP1B3)-based genetic switch system is designed and optimized to achieve near-infrared fluorescent imaging of miRNA by the uptake of indocyanine green (ICG) dye. The reporter system, named miR-ON-OB3, is shown to be efficient to regulate the expression of OATP1B3 in mammalian cells. Notably, the results indicate that the system is of high sensitivity for near-infrared fluorescence imaging of both exogenous and endogenous miRNA in mammalian cells. Moreover, the system is proved to be functional for real-time near-infrared fluorescence imaging of miRNA in living mice. This study establishes a novel genetic encoded reporter for near-infrared fluorescence imaging of miRNA, which may provide a potential tool for in vivo imaging of miRNA in clinical applications due to the clinical availability of ICG.

Minimally Invasive Percutaneous Leverage Reduction in the Treatment of Pediatric Salter-Harris IV and V Distal Femoral Physeal Fractures.

OBJECTIVE: Distal femoral physeal fractures (DFPF) are rare but severe injuries in children, and there is no consensus on treatments for Salter-Harris (S-H) IV and V type of DFPF yet. This study aimed to introduce a minimally invasive technique using percutaneous leverage reduction combined with Kirschner wires fixation in treating pediatric DFPF with S-H IV and V type of injury and evaluate the clinical results. METHODS: From July 2008 to June 2018, the authors' institute (Union Hospital, Tongji Medical College) retrospectively reviewed all patients diagnosed with pediatric DFPF. They were divided into two groups according to received treatment: children in the minimally invasive technique group were treated with a minimally invasive percutaneous leverage reduction technique, and the traditional technique group included the other children who received the conventional open reduction with internal fixation (ORIF). The surgical and clinical results of the two groups were collected and analyzed. The independent sample t-test analysis and the chi-square test were applied to compare continuous and categorical variables. RESULTS: A total of 14 pediatric patients were recruited, including five females and nine males with DFEF. All eight patients in the minimally invasive technique group and four of the six patients in the ORIF group were treated successfully. One patient in the minimally invasive technique group opted for conservative treatment due to his good functional recovery, while the other two patients in the ORIF group needed further surgery because of the limb length discrepancy. There was a difference in surgery duration (p < 0.001), intraoperative fluoroscopy numbers (p = 0.006), intraoperative blood loss (p < 0.001), radiological union time (p = 0.003) and knee flexion angle (p < 0.001) between two groups. Patients in the minimally invasive technique group all received total knee society (KSS) scores, while the average scores in the ORIF group were lower (100.00 vs. 97.67). CONCLUSION: The minimally invasive technique is better than conventional ORIF in terms of surgery duration, intraoperative blood loss, radiological union time, knee flexion angle and average KSS score. This percutaneous leverage reduction technique might be a good alternative for treating S-H IV and V DFPF in children.