Advancing Superconductivity with Interface Engineering.

The development of superconducting materials has attracted significant attention not only for their improved performance, such as high transition temperature (TC), but also for the exploration of their underlying physical mechanisms. Recently, considerable efforts have been focused on interfaces of materials, a distinct category capable of inducing superconductivity at non-superconducting material interfaces or augmenting the TC at the interface between a superconducting material and a non-superconducting material. Here, two distinct types of interfaces along with their unique characteristics are reviewed: interfacial superconductivity and interface-enhanced superconductivity, with a focus on the crucial factors and potential mechanisms responsible for enhancing superconducting performance. A series of materials systems is discussed, encompassing both historical developments and recent progress from the perspectives of technical innovations and the exploration of new material classes. The overarching goal is to illuminate pathways toward achieving high TC, expanding the potential of superconducting parameters across interfaces, and propelling superconductivity research toward practical, high-temperature applications.

Nanobody-based strategy for rapid and accurate pathogen detection: A case of COVID-19 testing.

Antibody pairs-based immunoassay platforms served as essential and effective tools in the field of pathogen detection. However, the cumbersome preparation and limited detection sensitivity of antibody pairs challenge in establishment of a highly sensitive detection platform. In this study, using COVID-19 testing as a case, we utilized readily accessible nanobodies as detection antibodies and further proposed an accurate design concept with a more scientific and efficient screening strategy to obtain ultrasensitive antibody pairs. We employed nanobodies capable of binding different antigenic epitopes of the nucleocapsid (NP) or receptor-binding domain (RBD) antigens sandwich as substitutes for monoclonal antibodies (mAbs) sandwich in fast detection formats and utilized time-resolved fluorescence (TRF) microspheres as the signal probe. Consequently, we developed a multi-epitope nanobody sandwich-based fluorescence lateral flow immunoassay (FLFA) strip. Our results suggest that the NP antigen had a detection limit of 12.01pg/mL, while the RBD antigen had a limit of 6.51 pg/mL using our FLFA strip. Based on double mAb sandwiches, the values presented herein demonstrated 4 to 32-fold enhancements in sensitivity, and 32 to 256-fold enhancements compared to commercially available antigen lateral flow assay kits. Furthermore, we demonstrated the excellent characteristics of the proposed test strip, including its specificity, stability, accuracy, and repeatability, which underscores its the prospective utility. Indeed, these findings indicate that our established screening strategy along with the multi-epitope nanobody sandwich mode provides an optimized strategy in the field of pathogen detection.

VolcanoSV enables accurate and robust structural variant calling in diploid genomes from single-molecule long read sequencing.

Structural variants (SVs) significantly contribute to human genome diversity and play a crucial role in precision medicine. Although advancements in single-molecule long-read sequencing offer a groundbreaking resource for SV detection, identifying SV breakpoints and sequences accurately and robustly remains challenging. We introduce VolcanoSV, an innovative hybrid SV detection pipeline that utilizes both a reference genome and local de novo assembly to generate a phased diploid assembly. VolcanoSV uses phased SNPs and unique k-mer similarity analysis, enabling precise haplotype-resolved SV discovery. VolcanoSV is adept at constructing comprehensive genetic maps encompassing SNPs, small indels, and all types of SVs, making it well-suited for human genomics studies. Our extensive experiments demonstrate that VolcanoSV surpasses state-of-the-art assembly-based tools in the detection of insertion and deletion SVs, exhibiting superior recall, precision, F1 scores, and genotype accuracy across a diverse range of datasets, including low-coverage (10x) datasets. VolcanoSV outperforms assembly-based tools in the identification of complex SVs, including translocations, duplications, and inversions, in both simulated and real cancer data. Moreover, VolcanoSV is robust to various evaluation parameters and accurately identifies breakpoints and SV sequences.

Zinc-doped C4N3/BiOBr S-scheme heterostructured hollow spheres for efficient photocatalytic degradation of tetracycline.

Photocatalytic degradation of organic pollutants in water is of great significance to the sustainable development of the environment, but encounters limited efficiency when a single compound is used. Thus, there have been enormous efforts to find novel photocatalytic heterostructured composites with high performance. In this work, a novel S-scheme heterostructure is constructed with BiOBr and Zn2+ doped C4N3 (Zn-C4N3) by a solvothermal method for efficient photodegradation of tetracycline (TC), a residual antibiotic difficult to be removed from the aquatic environment. Thanks to Zn2+-doping induced improvement in chemical affinity between Zn-C4N3 and BiOBr, well-formed Zn-C4N3/BiOBr heterostructured hollow spheres are formed. This structure can efficiently suppress fast recombination of photogenerated electron-hole pairs to enhance the photocatalytic activity of BiOBr dramatically. At a room temperature of 25 °C and neutral pH 7, the catalyst can degrade a significant portion of TC pollutants within 30 min under visible light. Also, the Zn-C4N3/BiOBr heterostructure displays good stability after recycling experiments. Free radical capture experiments and ESR tests show that ˙O2- is the main active substance for photocatalytic degradation of TC. This study provides new insights for constructing heterostructures with an intimate interface between the two phases for photocatalytic applications.

Leisure Activity, Childhood Starvation, and Risk of Incident Diabetes in Older Adults: Evidence From a Chinese Nationwide Cohort Study.

OBJECTIVE: This study explores the impact of leisure activity and the association between childhood starvation and the risk of diabetes in older Chinese adults. DESIGN: Prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort study in China. SETTING AND PARTICIPANTS: A total of 4637 older adults aged ≥65 years, all with documented diabetes history, experiences of childhood starvation, and participation in leisure activities were recruited. METHODS: Childhood starvation exposure was assessed via self-reported responses from a structured questionnaire. The leisure activities were measured by 9 distinctive components and categorized into 3 distinct categories: productive activity, recreational activity, and sedentary activity. Diabetes status was determined by self-reported, physician-diagnosed cases during the follow-up period. Nonparametric survival models were employed for analysis. RESULTS: Over an average follow-up period of 4.3 years, 215 of 4637 participants (4.6%) reported a confirmed diagnosis of diabetes. Nonparametric survival models showed that those reporting childhood starvation had a higher risk of late-life diabetes [hazard ratio (HR) 1.72, 95% CI 1.21-2.44]. Engaging in productive activity (HR 0.90, 95% CI 0.83-0.99) and recreational activity (HR 0.88, 95% CI 0.77-1.00) was linked with a reduced risk of late-life diabetes. Sedentary activity did not show a significant effect. Further analysis highlighted the interactions effects of leisure activities on diabetes risk across different demographic and historical exposure subgroups. CONCLUSIONS AND IMPLICATIONS: Engaging in productive and recreational leisure activities was inversely associated with the risk of diabetes in older adults who experienced childhood starvation. Promoting such activities could be beneficial in mitigating long-term diabetes risk related to early-life nutritional deficiencies.

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

A Multifunctional Nanocatalytic Metal-Organic Framework as a Ferroptosis Amplifier for Mild Hyperthermia Photothermal Therapy.

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice.

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

Unlocking Efficiency: Minimizing Energy Loss in Electrocatalysts for Water Splitting.

Catalysts play a crucial role in water electrolysis by reducing the energy barriers for hydrogen and oxygen evolution reactions (HER and OER). Research aims to enhance the intrinsic activities of potential catalysts through material selection, microstructure design, and various engineering techniques. However, the energy consumption of catalysts has often been overlooked due to the intricate interplay among catalyst microstructure, dimensionality, catalyst-electrolyte-gas dynamics, surface chemistry, electron transport within electrodes, and electron transfer among electrode components. Efficient catalyst development for high-current-density applications is essential to meet the increasing demand for green hydrogen. This involves transforming catalysts with high intrinsic activities into electrodes capable of sustaining high current densities. This review focuses on current improvement strategies of mass exchange, charge transfer, and reducing electrode resistance to decrease energy consumption. It aims to bridge the gap between laboratory-developed, highly efficient catalysts and industrial applications regarding catalyst structural design, surface chemistry, and catalyst-electrode interplay, outlining the development roadmap of hierarchically structured electrode-based water electrolysis for minimizing energy loss in electrocatalysts for water splitting.

The Role of Traditional Chinese Medicines in the Treatment of Osteoporosis.

Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.

Profiling of m6A methylation in porcine intramuscular adipocytes and unravelling PHKG1 represses porcine intramuscular lipid deposition in an m6A-dependent manner.

Intramuscular fat (IMF) content is mainly determined by intramuscular preadipocyte adipogenesis. Epigenetic modifications are known to have a regulatory effect on IMF. As N6-methyladenosine (m6A) is the most abundant epigenetic modification in eukaryotic RNAs. In the present study, we used m6A methylation and RNA sequencing (seq) to identify the m6A-modified RNAs associated with the adipogenic differentiation of intramuscular preadipocytes. Among them, the expression and m6A level of phosphorylase kinase subunit G1 (PHKG1) were found to be significantly changed during adipogenesis. Further studies revealed that knockdown of the methylase METTL3 decreased the m6A methylation of PHKG1 and led to a reduction in PHKG1. Moreover, knockdown of PHKG1 promoted adipogenic differentiation by upregulating the expression of adipogenic genes. In addition, we found that the IMF content in the longissimus thoracis (LT) of Bamei (BM) pigs was greater than that in Large White (LW) pigs, whereas the m6A and PHKG1 expression levels were lower in BM pigs. These findings indicate that the m6A level and expression of PHKG1 were significantly correlated with IMF content and meat quality. In conclusion, this study sheds light on the mechanism by which m6A modification regulates IMF deposition.

Comparison analysis of bioactive metabolites in soybean, pea, mung bean, and common beans: reveal the potential variations of their antioxidant property.

This study showed the significantly differences of basic nutrients and metabolite compounds in nine types of beans involved in soybean, mung bean, pea, and common beans. The metabolomics results showed that serval metabolites such as histidine, proline, 3-alanine, and myricetin which could be used to identify different beans. The random forest model showed that amino acid and fatty acid could be used as special indexes to distinguish different types of beans in practice. The different expressed metabolites among different types of beans were involved in various pathways including alanine, aspartate and glutamate metabolism, arginine and proline metabolism, and purine metabolism. The antioxidant activity was significantly different among different types of beans, and the contents of amino acid, coumarin, and polyphenol contributed the antioxidant activities of beans. Together, these results will provide a comprehensive understanding of metabolites in different types of beans and theoretical guideline for the future application of beans.

Primary Robotic Versus Conventional Laparoscopic Roux-en-Y Gastric Bypass in Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Robotic Roux-en-Y gastric bypass (RRYGB) and conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) are commonly performed as primary bariatric procedures. The aim of this article was to assess the role of RRYGB in patients undergoing primary bariatric procedures. METHODS: All of the qualified studies were selected from the PubMed, Embase, and Web of Science databases, etc. We mainly compared the outcomes and safety between RRYGB and LRYGB. The outcomes evaluation included surgical effect and surgical safety. RESULT: In total, 35 studies containing 426,463 patients were selected. The mortalities of patients adopting these 2 bariatric procedures were similar (RRYGB: 59/28,023, 0.21%; LRYGB: 612/397,945, 0.15%). We found no significant difference between RRYGB and LRYGB in the incidence of postoperative complications (30-day: OR=1.06, P =0.18; 1-y: OR=1.06, P =0.92). The incidence of 30-day readmission after the operation was higher in RRYGB patients (OR=1.24, P =0.003). However, we found that the RRYGB group had a lower incidence of anastomotic stricture 1 year after the operation when compared with LRYGB (OR=0.35, P =0.0004). The 1-year %EBMIL of these 2 groups was similar (78.53% vs. 76.02%). There was no significant difference in length of hospital stay (LOS) (WMD=-0.03d, P =0.59), conversion rate (OR=0.84, P =0.75), or anastomotic leak (OR=1.00, P =0.99) between these 2 groups. The mean hospital charges were higher in the RRYGB group ($11234.75 vs. $9468.58). CONCLUSION: This systematic review and meta-analysis showed no significant advantage of RRYGB in surgical effect or reduction of intraoperative complications. RRYGB may reduce the incidence of some postoperative long-term complications. The mean hospital charges of RRYGB were higher.

The role of traditional Chinese medicine on fracture surgery, hospitalization, and total mortality risks in diabetic patients with osteoporosis.

BACKGROUND: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. METHODS: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. RESULTS: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). CONCLUSION: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.

Ancient genomes revealed the complex human interactions of the ancient western Tibetans.

The western Tibetan Plateau is the crossroad between the Tibetan Plateau, Central Asia, and South Asia, and it is a potential human migration pathway connecting these regions. However, the population history of the western Tibetan Plateau remains largely unexplored due to the lack of ancient genomes covering a long-time interval from this area. Here, we reported genome-wide data of 65 individuals dated to 3,500-300 years before present (BP) in the Ngari prefecture. The ancient western Tibetan Plateau populations share the majority of their genetic components with the southern Tibetan Plateau populations and have maintained genetic continuity since 3,500 BP while maintaining interactions with populations within and outside the Tibetan Plateau. Within the Tibetan Plateau, the ancient western Tibetan Plateau populations were influenced by the additional expansion from the south to the southwest plateau before 1,800 BP. Outside the Tibetan Plateau, the western Tibetan Plateau populations interacted with both South and Central Asian populations at least 2,000 years ago, and the South Asian-related genetic influence, despite being very limited, was from the Indus Valley Civilization (IVC) migrants in Central Asia instead of the IVC populations from the Indus Valley. In light of the new genetic data, our study revealed the complex population interconnections across and within the Tibetan Plateau.

Maize grain filling characteristics in China: Response to meteorological factors.

To investigate the dynamic changes in dry matter accumulation in maize after anthesis, we established a logistic model to describe grain filling characteristics (GFC), and analyzed differences between spring and summer maize, and the influence of meteorological factors. The results showed that the logistic model accurately simulated the dynamic changes in grain growth. For spring maize, the fitted hundred-grain weight at maturity was closely related to the average grain filling rate until maturity, days of the active grain filling period, time of the maximum grain filling rate, and duration of the rapid increase in grain weight. For summer maize, it was closely related to the time of the maximum grain filling rate, days of active grain filling period, duration of gradual grain weight, and the rapidly increasing period. The filling characteristics of spring and summer maize differed because of the different meteorological conditions and biological characteristics. The grain filling duration of spring maize was longer than that of summer maize. The maximum grain filling rate of spring maize occurred later than that of summer maize. Temperature and precipitation were the main meteorological factors affecting the hundred-grain weight of spring maize, whereas temperature was the main factor affecting summer maize. The response of spring maize GFC to meteorological factors was more complex than that of summer maize. These results are important for the development of appropriate strategies for improving maize productivity in China.

Toward the Briarane Core via 1,3-Dipolar Cycloaddition.

The complete C20 framework of brianthein W was established, featuring hydroboration/allylation, to provide the C1-C2 quaternary/tertiary stereoarray with excellent stereocontrol. Intramolecular nitrile oxide cycloaddition (INOC) was adopted as the key transformation to establish the trans-fused 6/10-bicyclic ring system. Evolution of the second INOC event revealed the intricacies governing regioselectivity, which ultimately led to construction of the highly strained 10-membered carbocycle.

Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3000 Inherited Retinal Disease Patients from the United Kingdom.

Purpose: To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients. Design: Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients. Participants: Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019. Methods: Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire imaging dataset. Main Outcome Measures: Quantitative FAF imaging features including area in mm 2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. Results: A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM , ABCC6 , ABCA4 , RDH12 , and RPE65 , with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm 2 . The five genes with the largest hyper-AF areas were BEST1 , CDH23 , RDH12 , MYO7A , and NR2E3 , with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm 2 respectively. The five genes with largest ring areas were CDH23 , NR2E3 , CRX , EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm 2 . Vessel density was found to be highest in EFEMP1 , BEST1 , TIMP3 , RS1 , and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes ( RPGR, USH2A, RHO, EYS ) found EYS to be the fastest progressor at -0.18 mm 2 /year. Conclusions: We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.

Circular ZDHHC11 supports Burkitt lymphoma growth independent of its miR-150 binding capacity.

We previously showed that MYC promoted Burkitt lymphoma (BL) growth by inhibiting the tumor suppressor miR-150, resulting in release of miR-150 targets MYB and ZDHHC11. The ZDHHC11 gene encodes three different transcripts including a mRNA (pcZDHHC11), a linear long non-coding RNA (lncZDHHC11) and a circular RNA (circZDHHC11). All transcripts contain the same region with 18 miR-150 binding sites. Here we studied the relevance of circZDHHC11, including this miR-150 binding site region, for growth of BL cells. CircZDHHC11 was mainly present in the cytoplasmic fraction in BL cells and its localization was not altered upon miR-150 overexpression. Knockdown of circZDHHC11 caused a strong inhibition of BL growth without affecting the expression levels of MYC, MYB, miR-150 and other genes. Overexpression of circZDHHC11 neither affected cell growth, nor rescued the phenotype induced by miR-150 overexpression. Genomic deletion of the miR-150 binding site region did not affect growth, nor did it change the effect of circZDHHC11 knockdown. This indicated that the miR-150 binding site region is dispensable for the growth promoting role of circZDHHC11. To conclude, our results show that circZDHHC11 is a crucial factor supporting BL cell growth independent of its ability to sponge miR-150.

Bioavailability and mechanisms of dietary polyphenols affected by non-thermal processing technology in fruits and vegetables.

Plant polyphenols play an essential role in human health. The bioactivity of polyphenols depends not only on their content but also on their bioavailability in food. The processing techniques, especially non-thermal processing, improve the retention and bioavailability of polyphenolic substances. However, there are limited studies summarizing the relationship between non-thermal processing, the bioavailability of polyphenols, and potential mechanisms. This review aims to summarize the effects of non-thermal processing techniques on the content and bioavailability of polyphenols in fruits and vegetables. Importantly, the disruption of cell walls and membranes, the inhibition of enzyme activities, free radical reactions, plant stress responses, and interactions of polyphenols with the food matrix caused by non-thermal processing are described. This study aims to enhance understanding of the significance of non-thermal processing technology in preserving the nutritional properties of dietary polyphenols in plant-based foods. It also offers theoretical support for the contribution of non-thermal processing technology in improving food nutrition.