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Abstract This paper proposes a maximum torque per ampere (MTPA) control method for a permanent magnet reluctance hybrid rotor dual stator synchronous motor (PMRHRDSSM) based on a sliding mode speed controller, in response to the complex and special electromagnetic relationship of the motor. The paper focuses on the special electromagnetic relationship of PMRHRDSSM with stator winding series structure. Firstly, the trajectory equation of PMRHRDSSM MTPA stator current vector is derived, and based on the relationship between PMRHRDSSM torque and reluctance dq‐axis current, a PMRHRDSSM current controller that meets MTPA constraints is designed. Afterwards, a PMRHRDSSM sliding mode speed controller was designed with input speed error and output reference torque. Finally, an experimental platform for the proposed control method was established, and the control method was experimentally validated.

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

Fusarium species are the dominant cause of maize ear rot, but they also inflict serious damage to the roots and stalks. Theoretically, the organ where the host interacts with the pathogen most frequently should exhibit the highest degree of symptom-genotype correlation. Because that symptom-genotype correlation is an indicator reflecting the degree of coevolution between pathogen and its hosts. We wonder which organ is the main battlefield for the antagonism between maize and Fusarium. For this purpose, 43 isolates of Fusarium were isolated from infected maize ears. Fusarium verticillioides and F. graminearum are the two dominant pathogens, accounting for 44% and 30%, respectively. Furthermore, 14 elite maize inbreds were exposed to 43 Fusarium isolates and the symptoms of ear rot, stalk rot and root rot were investigated. In general, symptoms caused by F. graminearum were significantly more severe than those caused by other Fusarium species. Surprisingly, the genotype of F. verticillioides showed a strong correlation with stalk and root rot, but not with ear rot. Accordingly, our study may provide the first evidence that the stalk and root of maize, rather than the ear, is the main battlefield for the coevolution between maize and F. verticillioides.

Background: The association between frailty and sex hormone-binding globulin (SHBG) or insulin-like growth factor-1(IGF-1) levels demonstrates sex differences with inconsistent conclusions. This study aims to explore the causal relationship between frailty and SHBG or IGF-1 levels through bidirectional Mendelian randomization (MR). Methods: We conducted two-sample bidirectional sex-stratified MR analyses using summary-level data from genome-wide association studies (GWASs) to examine the causal relationship between frailty and IGF-1 or SHBG levels, as measured by frailty index (FI) and frailty phenotype (FP). We use the random-effects inverse-variance weighted (IVW), weighted median, MR-Egger, MR-Egger intercept, and leave-one-out approaches. Result: The relationship between frailty and SHBG or IGF-1 levels is inversely related, with a significant decrease in SHBG levels in females. Specifically, SHBG levels significantly decrease with FI (β = −5.49; 95 % CI: −9.67 to −1.32; FDR = 0.02) and more pronounced with FP (β = −10.14; 95 % CI: −16.16 to −4.13; FDR = 0.01), as determined by the IVW approach. However, reverse analysis shows no significant effect of IGF-1 or SHBG levels on either FI or FP (p > 0.05). Conclusion: Our study indicates a negative correlation between frailty and the levels of SHBG and IGF-1. It is suggested that further research is required to establish cut-off values for SHBG and IGF-1 levels in the frailty population. This is particularly important for females at higher risk, such as those undergoing menopause, to enable comprehensive assessment and early prevention efforts. While the findings imply that reduced IGF-1 and SHBG levels may not directly contribute to frailty, it is important not to overlook the underlying mechanisms through which they may indirectly influence frailty.

Abstract Background Analyzing the glaucoma burden in "Belt and Road" (B&R) countries based on age, gender, and risk factors from 1990 to 2019 in order to provide evidence for future prevention strategies. Methods We applied global burden of disease(GBD) 2019 to compare glaucoma prevalence and Years lived with disabilities (YLDs) from 1990 to 2019 in the B&R countries. Trends of disease burden between 1990 and 2019 were evaluated using the average annual percent change and the 95% uncertainty interval (UI) were reported. Results From 1990 to 2019, most B&R countries showed a downward trend in age-standardized prevalence and YLDs (all P 85 years), Malaysia(75–84 years), Brunei Darussalam(45–49 years), Afghanistan(70–79 years). Finally, in all Central Asian countries, the age-standardized YLDs due to glaucoma caused by fasting hyperglycemia demonstrated have an increase between 1990 and 2019 (all P

Abstract Robust laser sources are a fundamental building block for contemporary information technologies. Originating from condensed-matter physics, the concept of topology has recently entered the realm of optics, offering fundamentally new design principles for lasers with enhanced robustness. In analogy to the well-known Majorana fermions in topological superconductors, Dirac-vortex states have recently been investigated in passive photonic systems and are now considered as a promising candidate for robust lasers. Here, we experimentally realize the topological Dirac-vortex microcavity lasers in InAs/InGaAs quantum-dot materials monolithically grown on a silicon substrate. We observe room-temperature continuous-wave linearly polarized vertical laser emission at a telecom wavelength. We confirm that the wavelength of the Dirac-vortex laser is topologically robust against variations in the cavity size, and its free spectral range defies the universal inverse scaling law with the cavity size. These lasers will play an important role in CMOS-compatible photonic and optoelectronic systems on a chip.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%. Of PDAC patients, 15%-20% are eligible for radical surgery. Gemcitabine is an important chemotherapeutic agent for patients with PDAC; however, the efficacy of gemcitabine is limited due to resistance. Therefore, reducing gemcitabine resistance is essential for improving survival of patients with PDAC. Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC. Methods: We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment. Then, co-IP, ChIP, ChIP-seq, transcriptome sequencing, and qPCR were used to determine the specific mechanism by which phospholipase D1 (PLD1) confers resistance to gemcitabine. Results: PLD1 combines with nucleophosmin 1 (NPM1) and triggers NPM1 nuclear translocation, where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor (IL7R) expression. Upon interleukin 7 (IL-7) binding, IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein, BCL-2, and induce gemcitabine resistance. The PLD1 inhibitor, Vu0155069, targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells. Conclusions: PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1, further promoting the downstream JAK1/STAT5/Bcl-2 pathway. Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.

Abstract Background Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance. Methods We established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editing, sphere formation assays, iron assays and luciferase assays were conducted to elucidate the mechanism. Results High-throughput drug screening of chemotherapy-resistant PDOs identified irbesartan, an angiotensin ‖ type 1 (AT1) receptor antagonist, which could synergistically enhance the ability of chemotherapy to kill PDAC cells. In vitro and in vivo validation using PDO, PDX and KPC mouse models showed that irbesartan efficiently sensitized PDAC tumors to chemotherapy. Mechanistically, we found that irbesartan decreased c-Jun expression by inhibiting the Hippo/YAP1 pathway and further overcame chemotherapy resistance in PDAC. We also explored c-Jun, a potential target of irbesartan, which can transcriptionally upregulate the expression of key genes involved in stemness maintenance (SOX9/SOX2/OCT4) and iron metabolism (FTH1/FTL/TFRC). More importantly, we observed that PDAC patients with high levels of c-Jun expression demonstrated poor responses to the current standard chemotherapy regimen (gemcitabine plus nab-paclitaxel). Moreover, patients with PDAC had significant survival benefits from treatment with irbesartan plus a standard chemotherapy regimen in two-center retrospective clinical cohorts and patients with high c-Jun expression exhibited a better response to combination chemotherapy. Conclusions Irbesartan could be used in combination with chemotherapy to improve the therapeutic efficacy in PDAC patients with high levels of c-Jun expression. Irbesartan effectively inhibited chemotherapy resistance by suppressing the Hippo/YAP1/c-Jun/stemness/iron metabolism axis. Based on our findings, we are designing an investigator-initiated phase II clinical trial on the efficacy and safety of irbesartan plus a standard gemcitabine/nab-paclitaxel regimen in the treatment of patients with advanced III/IV staged PDAC and are hopeful that we will observe patient benefits.

Metallo-porphyrins with different metal centers display unique properties and are essential in various biological and chemical processes. Enormous efforts have been devoted to enriching the family of metallo-porphyrins on surfaces mainly through metalation processes within porphyrins and exogenous pure metals or intrinsic surface adatoms, which have focused on transition elements. However, less attention has been paid to the synthesis of alkali-metal-based porphyrins on a surface. Herein, by a combination of scanning tunneling microscopy (STM) imaging/manipulations and density functional theory (DFT) calculations, we report the fabrication of Na-porphyrins on Au(111) by introducing NaCl, i.e., two double-layered Na-centered porphyrins. Moreover, the interconversion between them was realized by precise STM manipulations. Our results demonstrate the feasibility of metalation by applying inorganic salt, which would serve as a promising strategy to embed intramolecular metal components into porphyrins for further functionalization and modification.

ObjectivesDue to the increase in life expectancy and the aging of the global population, the “Belt and Road” (“B&R”) countries are faced with varying degrees of lung cancer threat. The purpose of this study is to analyze the differences in the burden and trend of lung cancer disability in the “B&R” countries from 1990 to 2019 so as to provide an analytical strategic basis to build a healthy “B&R”.MethodsData were derived from the Global Burden of Disease 2019 (GBD 2019). Incidence, mortality, prevalence, the years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lung cancer and those attributable to different risk factors were measured from 1990 to 2019. Trends of disease burden were estimated by using the average annual percent change (AAPC), and the 95% uncertainty interval (UI) was reported.ResultsChina, India, and the Russian Federation were the three countries with the highest burden of lung cancer in 2019. From 1990 to 2019, the AAPC of incidence, prevalence, mortality, and DALYs generally showed a downward trend in Central Asia (except Georgia) and Eastern Europe, while in China, South Asia (except Bangladesh), most countries in North Africa, and the Middle East, the trend was mainly upward. The AAPC of age-standardized incidence was 1.33% (1.15%–1.50%); the AAPC of prevalence, mortality, and DALYs from lung cancer in China increased by 24% (2.10%–2.38%), 0.94% (0.74%–1.14%), and 0.42% (0.25%–0.59%), respectively. A downward trend of the AAPC values of age-standardized YLD rate in men was shown in the vast majority of “B&R” countries, but for women, most countries had an upward trend. For adults aged 75 years or older, the age-standardized YLD rate showed an increasing trend in most of the “B&R” countries. Except for the DALY rate of lung cancer attributable to metabolic risks, a downward trend of the DALY rate attributable to all risk factors, behavioral risks, and environmental/occupational risks was shown in the vast majority of “B&R” countries.ConclusionThe burden of lung cancer in “B&R” countries varied significantly between regions, genders, and risk factors. Strengthening health cooperation among the “B&R” countries will help to jointly build a community with a shared future for mankind.

Medicinal and edible seed Semen Persicae is susceptible to mycotoxin and fungal contamination. However, the occurrence of mycotoxin contamination and fungal infection is still unclear. In this paper, ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry and high-throughput sequencing were conducted to determine the mycotoxin contents and fungal abundances of Semen Persicae. 42.86% of samples were positive for aflatoxin B1 (26.48–48.37 μg/kg) and 28.57% of samples were positive for aflatoxin B2 (1.47–4.82 μg/kg). Ochratoxin A and fumonisin B1 were only detected in one sample (91.02 and 34.61 μg/kg, respectively). Chao 1 and Shannon indices were significantly higher in the Dalian of Liaoning, Baotou of Innermongolia and Langfang of Hebei regions than in other groups. Ascomycota, Basidiomycota, Wallemia, Candica, Saccharomyces and Aspergillus were the predominant fungi and they were significantly region-specific. Simultaneously, the diversity, composition and co-occurrence network complexity in the mycotoxin-free group were significantly higher than those in the mycotoxin-contaminated group. Spearman correlation analysis showed aflatoxins, ochratoxin A and fumonisins contents were positively and significantly correlated with the abundances of Aspergillus, Rhodotorula, Wallemia and Candida. In conclusion, this study reported the prevalence of mycotoxin contamination and the great diversity of fungi associated with Semen Persicae for the first time, providing an early warning for subsequent potential mycotoxin biosynthesis.

IntroductionArecae semen, which is derived from the dried ripe seed of Areca catechu L., has been commonly used as one of the major traditional Chinese medicines (TCMs). Three types of crude herbal preparations, namely, raw Arecae semen (AS), Arecae semen tostum (SAS), and Arecae semen carbonisata (FAS), are available for different clinical applications in TCMs. Although aflatoxin contamination in Arecae semen has been reported preliminarily, only a few studies have been conducted on fungal contamination.MethodsIn this study, the presence of fungi on the surface of three Arecae semen (AS, SAS, and FAS) that collected from four provinces were investigated using high-throughput sequencing and internal transcribed spacer 2.ResultsResults showed that the phyla Ascomycota (75.45%) and Basidiomycota (14.29%) and the genera Wallemia (7.56%), Botryosphaeria (6.91%), Davidiella (5.14%), and Symbiotaphrina (4.87%) were the dominant fungi, and they presented significant differences in four areas and three processed products (p

Developing high-activity, Nobel metal-free electrodes is of utmost significance in the context of the hydrogen evolution reaction (HER). In this study, we employed an electrodeposited process to fabricate Ni-Sn-P films on a copper substrate. The microstructure and electrocatalytic properties of these Ni-Sn-P films were thoroughly characterized and subsequently compared to those of the reference Ni-P films.Remarkably, the Ni-Sn-P electrode exhibited an impressively low overpotential of −84 mV at a current density of −10 mA cm ^−2 in a 1 M NaOH solution. This value was found to be 172 mV lower than that of the Ni-P electrode, thereby establishing the superior electrocatalytic activity of the Ni-Sn-P electrode. Moreover, the excellent electrocatalytic stability of the Ni-Sn-P electrode was demonstrated over a time span of at least 25 h.The exceptional attributes of the Ni-Sn-P electrode can be ascribed to its larger active surface area, lower Tafel slope, and reduced charge transfer resistance. The utilization of Ni-Sn-P films as electrode materials holds great potential in advancing the field of HER due to their enhanced performance compared to conventional Ni-P films.

BackgroundCongenital birth defects (CBDs) are a major public health issue. This study aims to assess trends in the burden of CBDs between 1990 and 2019 across China based on the Global Burden of Disease Study 2019 (GBD 2019).MethodsIndicators of the burden of CBDs included incidence, mortality, and disability-adjusted life years (DALYs). Metrics included number, rate, and age-standardized rate with 95% uncertainty intervals (UIs). Data were stratified by region [China, global, high-, middle-, low-socio-demographic index (SDI)], age, sex, and type of CBD. Average annual percentage changes (AAPC) and trends were evaluated.ResultsIn China, between 1990 and 2019, the age-standardized incidence rate for CBDs showed an increasing trend, with an AAPC of 0.26% (0.11% to 0.41%), reaching 148.12 per 105 person-years (124.03 to 176.33) in 2019. Most CBDs were congenital heart anomalies, with an AAPC of 0.12% (−0.08% to 0.32%). The age-standardized mortality rate for CBDs showed a decreasing trend, with an AAPC of −4.57% (−4.97% to −4.17%), reaching 4.62 per 105 person-years (3.88 to 5.57) in 2019. Most mortality was associated with congenital heart anomalies, with an AAPC of −3.77% (−4.35% to −3.19%). The age-standardized DALYs rate for CBDs showed a decreasing trend, with an AAPC of −3.74% (−3.95% to −3.52%), reaching 480.95 per 105 person-years (407.69 to 570.04) in 2019.ConclusionsMorbidity associated with CBDs increased in China between 1990 and 2019, accelerated by the adoption of the two-child policy, and ranked high globally. These findings emphasize the need for prenatal screening and primary and secondary prevention strategies.

The widespread prevalence of infectious bacteria is one of the greatest threats to public health, and consequently, there is an urgent need for efficient and broad-spectrum antibacterial materials that are antibiotic-free. In this study, 2-pyridinecarboxaldehyde (PCA) was grafted onto chitosan (CS) and the modified CS coordinated with silver ions to prepare PCA-CS-Ag complexes with antibacterial activity. To obtain complexes with a high silver content, the preparation process was optimized using single-factor experiments and response surface methodology. Under the optimal preparation conditions (an additional amount of silver nitrate (58 mg), a solution pH of 3.9, and a reaction temperature of 69 °C), the silver content of the PCA-CS-Ag complex reached 13.27 mg/g. The structure of the PCA-CS-Ag complex was subsequently verified using ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. Furthermore, three possible complexation modes of the PCA-CS-Ag complex were proposed using molecular mechanics calculations. The results of the antibacterial assay in vitro showed that the PCA-CS-Ag complex exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria, exerting the synergistic antibacterial effect of modified chitosan and silver ions. Therefore, the PCA-CS-Ag complex is expected to be developed as an effective antibacterial material with promising applications in food films, packaging, medical dressings, and other fields.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and an adaptor protein that primarily regulates adhesion signaling and cell migration. FAK promotes cell survival in response to stress. Increasing evidence has shown that at the pathological level, FAK is highly expressed in multiple tumors in several systems (including lung, liver, gastric, and colorectal cancers) and correlates with tumor aggressiveness and patient prognosis. At the molecular level, FAK promotes tumor progression mainly by altering survival signals, invasive capacity, epithelial-mesenchymal transition, the tumor microenvironment, the Warburg effect, and stemness of tumor cells. Many effective drugs have been developed based on the comprehensive role of FAK in tumor cells. In addition, its potential as a tumor marker cannot be ignored. Here, we discuss the pathological and pre-clinical evidence of the role of FAK in cancer development; we hope that these findings will assist in FAK-based clinical studies.

Abstract Permanent magnet synchronous motor (PMSM) shows the great potential for use in direct drive system because of its excellent low‐speed direct‐drive capability. However, it suffers from the adverse effect of the cogging torque in comparison with the asynchronous motor. Therefore, reducing the cogging torque, especially the external‐rotor PMSM (ERPMSM) for belt conveyor application, is necessary for enhancing the stable operation and precise positioning performances of the belt conveyor.Herein, a novel tangential magnetization low‐speed high‐torque ERPMSM is proposed and analysed. Furthermore, the expression of the cogging torque of the proposed ERPMSM is derived by energy method. Based on the special structure of the ERPMSM, a new method for cogging torque reduction is introduced. The comparative FEA results for four ERPMSM models are presented to verify the accuracy and effectiveness of this method. The accuracy of the cogging torque FEA results is confirmed by a prototype. Finally, the influence of this method on ERPMSM performance is also analysed carefully in this paper.

PELATON is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 (LINC01272). The known reports showed that PELATON functions as an onco-lncRNA or a suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found that PELATON, as an onco-lncRNA, alleviates the ferroptosis driven by mutant p53 and promotes mutant p53-mediated GBM proliferation. We also first confirmed that PELATON is a new ferroptosis suppressor lncRNA that functions as a ferroptosis inhibitor mainly by mutant P53 mediating the ROS ferroptosis pathway, which inhibits the production of ROS, reduces the levels of divalent iron ions, promotes the expression of SLC7A11, and inhibits the expression of ACSL4 and COX2.PELATON can inhibit the expression of p53 in p53 wild-type GBM cells and regulate the expression of BACH1 and CD44, but it has no effect on p53, BACH1 and CD44 in p53 mutant GBM cells. PELATON and p53 can form a complex through the RNA binding protein EIF4A3. Knockdown of PELATON resulted in smaller mitochondria, increased mitochondrial membrane density, and enhanced sensitivity to ferroptosis inducers to inhibit GBM cell proliferation and invasion. In addition, we established a favourite prognostic model with NCOA4 and PELATON. PELATON is a promising target for the prognosis and treatment of GBM.

Objectives This study aimed at examining the extent of turnover intention among the Chinese resident physicians who entered the newly established national standardised residency training programme (SRTP), and exploring factors associated with their turnover intention.Design Cross-sectional survey.Setting Ten institutions from five geographical areas in China.Methods 1414 residents were surveyed using paper-based questionnaires and scales regarding their demographics, work situation, attitudes towards SRTP, job satisfaction, psychological resilience, burnout and turnover intention in 2017. The turnover intention was described and compared between categorical groups. Linear regressions were used to select the factors associated with turnover intention. The structural equation model was used to capture the potential mediating effects.Results The mean turnover intention score was 12.45 (SD=4.47). Nearly half (47.87%) of the residents had a high and very high level of turnover intention. Psychological resilience (β=0.066), burnout (β=0.141) and job satisfaction (β=0.022) were positively associated with turnover intention, while specialty (β=−0.135), year of training (β=−0.687), career in medicine (β=−2.191), necessity of training (β=−0.695) and satisfaction with income (β=−1.215) had negative associations with turnover intention. Working hours and nightshift interval indirectly were associated with turnover intention through the mediating effects of burnout. Career in medicine, necessity of training, satisfaction with income, and psychological resilience showed direct effects and indirect effects on turnover intention through burnout and job satisfaction as mediators.Conclusions The turnover intention among Chinese residents was prevalent and unignorable. Burnout was the major contributing factor, while year of training and positive attitudes towards training were protective factors. Burnout and job satisfaction also served as mediators. Interventions targeting these factors should be incorporated in the training programmes to keep a prosperous physician workforce.

Fabricating semiconductor photonic lasers based on III-V materials are challenging because of the material mismatch with silicon. Here the authors monolithically grow quantum-dot-based photonic crystal membrane lasers directly on an on-axis silicon substrate.

Background and Aims: N6-Methyladenosine (m6A) is the most common post-transcriptional modification on eukaryotic mRNA, affecting the mRNA’s fate. The role of m6A regulation in inflammatory bowel disease is unclear. Here, we investigated the m6A landscape in inflammatory bowel diseases (IBD).Methods: Eleven human IBD microarray datasets were recruited from the Gene Expression Omnibus database and four were selected as discovery cohorts. An RNA-seq dataset from the Inflammatory Bowel Disease Multi’omics Database was used as a validation cohort. m6A regulators were measured in volunteers’ colonic samples. Consensus clustering and immune scoring were used to estimate the characteristics of m6A regulation in IBD. m6A-related characteristics of different sub-phenotypes, sample sources, and biological therapeutic responses were determined using seven independent datasets.Results: m6A modification involves methyltransferases (writers), demethylases (erasers), and methylation-reading proteins (readers). A wide interaction exists between m6A regulators and IBD risk genes. The IBD risk loci can also be modified by m6A modifications in the public m6A sequencing data. Furthermore, m6A regulators displayed extensive differential expression in four independent discovery cohorts that share common differential genes (IGF2BP2, HNRNPA2B1, ZCCHC4, and EIF3I). In the validated cohort and enrolled volunteers’ colonic biopsy samples, the differential m6A regulators were reconfirmed. Two clusters of consensus clustering exhibit different immune phenotypes. m6A-modified positions exist in the core IBD immune cytokines. Another set of IBD datasets revealed m6A-related differences across clinical phenotypes, biological samples, and therapeutic response subgroups in IBD patients.Conclusion: Regulation of m6A methylation is widely involved in IBD occurrence and development. m6A modifications in risk variants, core cytokines, immune cells, and other proteins may deeply influence the pathophysiology and clinical phenotypes. Further studies are needed to determine its role in IBD.

We study a new technique for solving the fundamental challenge in nanophotonic design: fast and accurate characterization of nanoscale photonic devices with minimal human intervention. Much like the fusion between Artificial Intelligence and Electronic Design Automation (EDA), many efforts have been made to apply deep neural networks (DNN) such as convolutional neural networks to prototype and characterize next-gen optoelectronic devices commonly found in Photonic Integrated Circuits. However, state-of-the-art DNN models are still far from being directly applicable in the real world: e.g., DNN-produced correlation coefficients between target and predicted physical quantities are about 80%, which is much lower than what it takes to generate reliable and reproducible nanophotonic designs. Recently, attention-based transformer models have attracted extensive interests and been widely used in Computer Vision and Natural Language Processing. In this work, we for the first time propose a Transformer model (POViT) to efficiently design and simulate photonic crystal nanocavities with multiple objectives under consideration. Unlike the standard Vision Transformer, our model takes photonic crystals as input data and changes the activation layer from GELU to an absolute-value function. Extensive experiments show that POViT significantly improves results reported by previous models: correlation coefficients are increased by over 12% (i.e., to 92.0%) and prediction errors are reduced by an order of magnitude, among several key metric improvements. Our work has the potential to drive the expansion of EDA to fully automated photonic design (i.e., PDA). The complete dataset and code will be released to promote research in the interdisciplinary field of materials science/physics and computer science.

Photoacoustic spectroscopy can generate abundant chemical and physical information about biological tissues. However, this abundance of information makes it difficult to compare these tissues directly. Data mining methods can circumvent this problem. We describe the application of machine-learning methods (including unsupervised hierarchical clustering and supervised classification) to the diagnosis of prostate cancer by photoacoustic spectrum analysis. We focus on the content and distribution of hemoglobin, collagen, and lipids, because these molecules change during the development of prostate cancer. A higher correlation among the ultrasonic power spectra of these chemical components is observed in cancerous than in normal tissues, indicating that the microstructural distributions in cancerous tissues are more consistent. Different classifiers applied in cancer-tissue diagnoses achieved an accuracy of 82 % (better than that of standard clinical methods). The technique thus exhibits great potential for painless early diagnosis of aggressive prostate cancer.

The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

The design of nanophotonic structures based on deep learning is emerging rapidly in the research community. Design methods using Deep Neural Networks (DNN) are outperforming conventional physics-based simulations performed iteratively by human experts. Here, a self-adaptive and regularized DNN based on Convolutional Neural Networks (CNNs) for the smart and fast characterization of nanophotonic structures in high-dimensional design parameter space is presented. This proposed CNN model, named LRS-RCNN, utilizes dynamic learning rate scheduling and L2 regularization techniques to overcome overfitting and speed up training convergence and is shown to surpass the performance of all previous algorithms, with the exception of two metrics where it achieves a comparable level relative to prior works. We applied the model to two challenging types of photonic structures: 2D photonic crystals (e.g., L3 nanocavity) and 1D photonic crystals (e.g., nanobeam) and results show that LRS-RCNN achieves record-high prediction accuracies, strong generalizibility, and substantially faster convergence speed compared to prior works. Although still a proof-of-concept model, the proposed smart LRS-RCNN has been proven to greatly accelerate the design of photonic crystal structures as a state-of-the-art predictor for both Q-factor and V. It can also be modified and generalized to predict any type of optical properties for designing a wide range of different nanophotonic structures. The complete dataset and code will be released to aid the development of related research endeavors.

We consider a general class of mean field control problems described by stochastic delayed differential equations of McKean–Vlasov type. Two numerical algorithms are provided based on deep learning techniques, one is to directly parameterize the optimal control using neural networks, the other is based on numerically solving the McKean–Vlasov forward anticipated backward stochastic differential equation (MV-FABSDE) system. In addition, we establish the necessary and sufficient stochastic maximum principle of this class of mean field control problems with delay based on the differential calculus on function of measures, and the existence and uniqueness results are proved for the associated MV-FABSDE system under suitable conditions.Mathematical Subject Classification (2000): 93E20, 60G99, 68-04

Chitosan is a linear polysaccharide produced by deacetylation of natural biopolymer chitin. Owing to its good biocompatibility and biodegradability, non-toxicity, and easy processing, it has been widely used in many fields. After billions of years of survival of the fittest, many organisms have already evolved a nearly perfect structure. This paper reviews the research status of biomimetic functional materials that use chitosan as a matrix material to mimic the biological characteristics of bivalves, biological cell matrices, desert beetles, and honeycomb structure of bees. In addition, the application of biomimetic materials in wound healing, hemostasis, drug delivery, and smart materials is briefly overviewed according to their characteristics of adhesion, hemostasis, release, and adsorption. It also discusses prospects for their application and provides a reference for further research and development.

A cantilever-based microring laser structure was proposed for easily integrating III-V active layer into mechanically stretchable substrates. Local strain gauges were demonstrated by embedding cantilever-based microring lasers in a deformable polymer substrate. The characterizations of microscale local strain gauges had been studied from both simulated and experimental results. The lasing wavelength of strain gauges was blue-shift and linear tuned by stretching the flexible substrate. Gauge factor being ∼11.5 nm per stretching unit was obtained for a cantilever-based microring laser with structural parameters R=1.25 μm, W1=450 nm and W2=240 nm. Such microring lasers embedded in a flexible substrate are supposed to function not only as strain gauges for monitoring the micro- or nano-structured deformation, but also tunable light sources for photonic integrated circuits.

We study a toy model of linear-quadratic mean field game with delay. We “lift” the delayed dynamic into an infinite dimensional space, and recast the mean field game system which is made of a forward Kolmogorov equation and a backward Hamilton-Jacobi-Bellman equation. We identify the corresponding master equation. A solution to this master equation is computed, and we show that it provides an approximation to a Nash equilibrium of the finite player game.