The MdHSC70-MdWRKY75 module mediates basal apple thermotolerance by regulating the expression of heat shock factor genes.

Heat stress severely restricts the growth and fruit development of apple (Malus domestica). Little is known about the involvement of WRKY proteins in the heat tolerance mechanism in apple. In this study, we found that the apple transcription factor MdWRKY75 responds to heat and positively regulates basal thermotolerance. Apple plants that overexpressed MdWRKY75 were more tolerant to heat stress, while silencing MdWRKY75 caused the opposite phenotype. RNA-seq and reverse transcription quantitative PCR showed that heat shock transcription factor genes (MdHsfs) could be the potential targets of MdWRKY75. Electrophoretic mobility shift, yeast one-hybrid, ß-glucuronidase, and dual-luciferase assays showed that MdWRKY75 can bind to the promoters of MdHsf4, MdHsfB2a, and MdHsfA1d and activate their expression. Apple plants that overexpressed MdHsf4, MdHsfB2a, and MdHsfA1d exhibited heat tolerance and rescued the heat sensitive phenotype of MdWRKY75-Ri3. In addition, apple heat shock cognate 70 (MdHSC70) interacts with MdWRKY75, as shown by yeast two-hybrid, split luciferase, bimolecular fluorescence complementation, and pull-down assays. MdHSC70 acts as a negative regulator of the heat stress response. Apple plants that overexpressed MdHSC70 were sensitive to heat, while virus-induced gene silencing of MdHSC70 enhanced heat tolerance. Additional research showed that MdHSC70 exhibits heat sensitivity by interacting with MdWRKY75 and inhibiting MdHsfs expression. In summary, we proposed a mechanism for the response of apple to heat that is mediated by the 'MdHSC70/MdWRKY75-MdHsfs' molecular module, which enhances our understanding of apple thermotolerance regulated by WRKY transcription factors.

Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and Sweden.

BACKGROUND: The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer. METHODS AND FINDINGS: We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations. The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; p = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; p = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; p = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; p < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; p = 0.03), and there was no altered risk of parental death by suicide any time after the child's cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings. CONCLUSIONS: In this study, we observed an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child's cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.

Clonal hematopoiesis of indeterminate potential and risk of neurodegenerative diseases.

BACKGROUND: Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases. OBJECTIVE: To estimate the risk of neurodegenerative diseases among individuals with CHIP. METHODS: We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP. RESULTS: We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01-1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05-1.63) and ALS (HR 1.50, 95% CI 1.05-2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97-1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96-1.17), AD (HR 1.04, 95% CI 0.88-1.23), and PD (HR 1.02, 95% CI 0.86-1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A-mutant CHIP, ASXL1-mutant CHIP, or SRSF2-mutant CHIP. CONCLUSION: Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.

MdERF114 enhances the resistance of apple roots to Fusarium solani by regulating the transcription of MdPRX63.

As the main fungal etiologic agent of apple (Malus domestica) replant disease (ARD), Fusarium solani seriously damages apple roots. Ethylene response factors (ERFs) play an important role in plant resistance to biotic stress. Here, we show that MdERF114 is expressed during F. solani infections and positively regulates the resistance of apple roots to F. solani. Yeast one-hybrid, dual-luciferase, electrophoretic mobility shift assays and determinations of lignin content indicated that MdERF114 directly binds the GCC-box of the MdPEROXIDASE63 (MdPRX63) promoter and activates its expression, resulting in lignin deposition in apple roots and increased resistance to F. solani. We identified a WRKY family transcription factor, MdWRKY75, that binds to the W-box of the MdERF114 promoter. Overexpression of MdWRKY75 enhanced resistance of apple roots to F. solani. MdMYB8 interacted with MdERF114 to enhance resistance to F. solani by promoting the binding of MdERF114 to the MdPRX63 promoter. In summary, our findings reveal that the MdWRKY75-MdERF114-MdMYB8-MdPRX63 module is required for apple resistance to F. solani and the application of this mechanism by Agrobacterium rhizogenes-mediated root transformation provides a promising strategy to prevent ARD.

Ostwald ripening for designing time-dependent crystal hydrogels.

Ostwald ripening (OR), a classic solution theory describing molecular transfer from metastable crystal to stable one, is applied to design time-dependent crystal hydrogels that can automatically change their mechanical properties. Using a system made from crosslinked polyacrylamide (PAM) and sodium acetate (NaAc), we demonstrate that metastable fibrous crystal networks of NaAc preferably form in PAM hydrogels via a polymer-involving mismatch nucleation. These fibrous crystals would undergo OR and evolve into isolated bulk crystals, leading to a significant reduction in material rigidity (179 folds) and interfacial adhesion (20 folds). This transformation can be applied to program time-dependent self-recovery in shape and self-delamination. Since OR is a ubiquitous, robust feature of various crystals, the approach reported here represents a new direction for designing advanced transient soft materials.

Potential role of the P2X7 receptor in the proliferation of human diffused large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of invasive non-Hodgkin lymphoma. 60-70% of patients are curable with current chemoimmunotherapy, whereas the rest are refractory or relapsed. Understanding of the interaction between DLBCL cells and tumor microenvironment raises the hope of improving overall survival of DLBCL patients. P2X7, a member of purinergic receptors P2X family, is activated by extracellular ATP and subsequently promotes the progression of various malignancies. However, its role in DLBCL has not been elucidated. In this study, the expression level of P2RX7 in DLBCL patients and cell lines was analyzed. MTS assay and EdU incorporation assay were carried out to study the effect of activated/inhibited P2X7 signaling on the proliferation of DLBCL cells. Bulk RNAseq was performed to explore potential mechanism. The results demonstrated high level expression of P2RX7 in DLBCL patients, typically in patients with relapse DLBCL. 2'(3')-O-(4-benzoylbenzoyl) adenosine 5-triphosphate (Bz-ATP), an agonist of P2X7, significantly accelerated the proliferation of DLBCL cells, whereas delayed proliferation was detected when administrated with antagonist A740003. Furthermore, a urea cycle enzyme named CPS1 (carbamoyl phosphate synthase 1), which up-regulated in P2X7-activated DLBCL cells while down-regulated in P2X7-inhibited group, was demonstrated to involve in such process. Our study reveals the role of P2X7 in the proliferation of DLBCL cells and implies that P2X7 may serve as a potential molecular target for the treatment of DLBCL.

In situ Nucleation-Growth Strategy for Controllable Heterogeneous Supramolecular Polymerization of Liquid Crystalline Block Copolymers and Their Hierarchical Assembly.

The self-assembly morphologies of subunits are largely governed by thermodynamics, which plays a less important role in dimensional control. Particularly for one-dimensional assemblies from block copolymers (BCPs), the negligible energy difference between short and long ones imposes great challenges in length control. Herein, we report that by incorporating additional polymers to induce in situ nucleation and trigger the subsequent growth, controllable supramolecular polymerization driven by mesogenic ordering effect could be realized from liquid crystalline BCPs. The length of the resultant fibrillar supramolecular polymers (SP) is controlled by tuning the ratio between nucleating and growing components. Depending on the choice of BCPs, the SPs can be homopolymer-like, heterogeneous triblock, and even pentablock copolymer-like. More interestingly, with insoluble BCP as a nucleating component, amphiphilic SPs are fabricated, which can undergo spontaneous hierarchical assembly.

Self-sorting assembly of artificial building blocks.

Self-assembly to build high-level structures, which is ubiquitous in living systems, has captured the imagination of scientists, striving to emulate the intricacy, homogeneity and versatility of the naturally occurring systems, and to pursue a similar level of organization in artificial building blocks. In particular, self-sorting assembly in multicomponent systems, based on the spontaneous recognition and consequent spatial aggregation of the same or interactive building units, is able to realize very complicated assembly behaviours, and usually results in multiple well-ordered products or hierarchical structures in a one-step manner. This highly efficient assembly strategy has attracted tremendous research attention in recent years, and numerous examples have been reported in artificial systems, particularly with supramolecular and polymeric building blocks. In the current review, we summarize the progress in recent years, and classify them into five main categories, based on their working mechanisms or principles. With the review of these strategies, we hope to provide not only some deep insights into this field, but also and more importantly, useful thoughts in the design and fabrication of self-sorting systems in the future.

Exogenous Dopamine and MdTyDC Overexpression Enhance Apple Resistance to Fusarium solani.

Fusarium solani, one of the main pathogenic fungi involved in apple replant disease (ARD), is a serious threat to apple growth and development. Dopamine and tyrosine decarboxylase (TyDC), a key enzyme in the dopamine synthesis pathway, have been reported to play an active role in plant responses to biotic and abiotic stresses, but little is known about the functions of dopamine and Malus domestica TyDC (MdTyDC) in the interaction between F. solani and apple roots. In this study, seedlings treated with exogenous dopamine and apple plants overexpressing MdTyDC were inoculated with F. solani; both treatments reduced the root system damage caused by F. solani. After inoculation with F. solani, exogenous dopamine increased dopamine content in the seedlings; alleviated the inhibition of biomass accumulation; increased root metabolic activity, photosynthetic efficiency, and antioxidant enzyme activities; reduced reactive oxygen species accumulation; and upregulated the expression of genes encoding chitinase, ß-1,3-glucanase, and pathogenesis-related proteins. Similar results were observed in MdTyDC-overexpressing apple plants. In addition, the overexpression of MdTyDC increased tyramine content and the deposition of cell wall-bound amines in roots. Overall, our results reveal that exogenous dopamine and overexpression of MdTyDC enhance apple resistance to F. solani, which is an important application for the prevention of ARD.

Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study.

BACKGROUND: A knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID. METHODS AND FINDINGS: We conducted a population-based cohort study of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. All individuals were followed from birth until cancer diagnosis, emigration, death, or 31 December 2016 (up to age 43 years), whichever came first. Incident cancers were identified from the Swedish Cancer Register. We fitted Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of cancer risk in relation to ID after adjusting for several potential confounders. We analyzed ID by severity, as well as idiopathic ID and syndromic ID separately. We performed a sibling comparison to investigate familial confounding. The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID. Compared with the reference group (individuals without ID and without a full sibling with ID), individuals with ID were in general more likely to be male. The median follow-up time was 8.9 and 23.0 years for individuals with ID and individuals without ID, respectively. A total of 188 cancer cases were identified among individuals with ID (incidence rate [IR], 62 per 1,000 person-years), and 24,960 among individuals in the reference group (IR, 31 per 1,000 person-years). A statistically significantly increased risk was observed for any cancer (HR 1.57, 95% CI 1.35-1.82; P < 0.001), as well as for several cancer types, including cancers of the esophagus (HR 28.4, 95% CI 6.2-130.6; P < 0.001), stomach (HR 6.1, 95% CI 1.5-24.9; P = 0.013), small intestine (HR 12.0, 95% CI 2.9-50.1; P < 0.001), colon (HR 2.0, 95% CI 1.0-4.1; P = 0.045), pancreas (HR 6.0, 95% CI 1.5-24.8; P = 0.013), uterus (HR 11.7, 95% CI 1.5-90.7; P = 0.019), kidney (HR 4.4, 95% CI 2.0-9.8; P < 0.001), central nervous system (HR 2.7, 95% CI 2.0-3.7; P < 0.001), and other or unspecified sites (HR 4.8, 95% CI 1.8-12.9; P = 0.002), as well as acute lymphoid leukemia (HR 2.4, 95% CI 1.3-4.4; P = 0.003) and acute myeloid leukemia (HR 3.0, 95% CI 1.4-6.4; P = 0.004). Cancer risk was not modified by ID severity or sex but was higher for syndromic ID. The sibling comparison showed little support for familial confounding. The main study limitations were the limited statistical power for the analyses of specific cancer types, and the potential for underestimation of the studied associations (e.g., due to potential underdetection or delayed diagnosis of cancer among individuals with ID). CONCLUSIONS: In this study, we found that individuals with ID showed an increased risk of any cancer, as well as of several specific cancer types. These findings suggest that extended surveillance and early intervention for cancer among individuals with ID are warranted.

Lewis base catalyzed regioselective cyclization of allene ketones or α-methyl allene ketones with unsaturated pyrazolones.

A nitrogen-containing Lewis base catalyzed highly regioselective [4 + 2] cycloaddition of allene ketones or α-methyl allene ketones with unsaturated pyrazolones has been disclosed to give the corresponding tetrahydropyrano [2,3-c] pyrazoles in moderate to good yields under mild conditions. High regioselectivity, 100% atom-economy, broad substrate scope and good functional group tolerance are attractive features of this process and make it a practical and versatile transformation.

The Dual-State Luminescent Mechanism of 2,3,4,5-Tetraphenyl-1H-pyrrole.

2,3,4,5-Tetraphenyl-1H-pyrrole (TePP) was synthesized by a simple one-step reaction. The compound showed a balanced emission in both the solution and solid state with the absolute quantum yield of ΦF/THF =65.6 % and ΦF/solid =74.3 %, respectively. Temperature and viscosity variation measurements demonstrated that the phenyl group at the 1-position (N-position) of the pyrrole core can act as a rotor in pyrrole-based molecules, which can consume the excited energy and reduce the molecular emission in solution. TePP without the phenyl group at the 1-position can effectively enhance the emission in solution. Single-crystal analysis showed that the phenyl groups at the 2,5-positions of pyrrole extend the molecular conjugation and lock the conformation. The phenyl groups at the 3,4-positions with a twisted conformation prevent their molecules from close packing and are helpful for aggregated emission. A delicate balance between the twisting conformation and rigid conjugation takes advantage of both ACQ and AIE luminogens. The strategy can tune the AIE, ACQ, or solution and solid dual-state emission properties of pyrrole-based molecules by simply altering the position of phenyl groups, which provides a great opportunity to explore the luminescent mechanism in greater detail and to facilitate practical applications.

The HD-Zip I transcription factor MdHB-7 negatively regulates resistance to Glomerella leaf spot in apple.

Glomerella leaf spot (GLS), caused by Colletotrichum fructicola (Cf), has been one of the main fungal diseases afflicting apple-producing areas across the world for many years, and it has led to substantial reductions in apple output and quality. HD-Zip transcription factors have been identified in several species, and they are involved in the immune response of plants to various types of biotic stress. In this study, inoculation of MdHB-7 overexpressing (MdHB-7-OE) and interference (MdHB-7-RNAi) transgenic plants with Cf revealed that MdHB-7, which encodes an HD-Zip transcription factor, adversely affects GLS resistance. The SA content and the expression of SA pathway-related genes were lower in MdHB-7-OE plants than in 'GL-3' plants; the content of ABA and the expression of ABA biosynthesis genes were higher in MdHB-7-OE plants than in 'GL-3' plants. Further analysis indicated that the content of phenolics and chitinase and ß-1, 3 glucanase activities were lower and H2O2 accumulation was higher in MdHB-7-OE plants than in 'GL-3' plants. The opposite patterns were observed in MdHB-7-RNAi apple plants. Overall, our results indicate that MdHB-7 plays a negative role in regulating defense against GLS in apple, which is likely achieved by altering the content of SA, ABA, polyphenols, the activities of defense-related enzymes, and the content of H2O2.

Precise Construction of Chiral Plasmonic Nanoparticles for Enantioselective Discrimination.

Chiral plasmonic nanostructures exhibit potential in the advanced manufacturing industry, due to their fascinating characteristics. However, the limitation of existing fabrication methods as difficulty to precisely manipulate chiral nanostructures at the nanoscale restricts their application and optimization of performance. In this work, we report a simple and robust route for the precise construction of chiral Au nanoparticles (NPs), employing star-like block copolymers with well-defined structures as chiral templates. The globular unimolecular micelles as nanoreactors enabled control over the size, shape, and chirality of in situ grown nanocrystals. Utilizing the chiral anisotropy property of surface-enhanced Raman scattering (SERS), the enantioselective discrimination on various substrates was accomplished with an enhancement factor over 9.3 × 106. NPs with a smaller size exhibited strengthened Raman enhancement and chiral recognition. Furthermore, these chiral unimolecular-micelle-based templates with high efficiency and strong controllability could pave the way for tailor-made chiral nanomaterials.

Suicide Attempt and Suicide Death Among Spouses of Patients With Cancer.

Importance: Little is known about the risk of suicidal behavior in relation to having a spouse with a cancer diagnosis. Objective: To estimate the risk of suicide attempt and suicide death among spouses of patients with cancer. Design, Setting, and Participants: This nationwide cohort study in Denmark collected registry-based data from 1986 through 2016. Analyses were performed from August 8, 2022, to October 30, 2023. Individuals who had a spouse with a cancer diagnosed during 1986 to 2015 were compared with individuals whose spouse did not have a cancer diagnosis during the same period, randomly selected from the general population and matched by birth year and sex. Exposure: Having a spouse with a cancer diagnosis. Main Outcomes and Measures: Suicide attempt was identified through the Danish National Patient Register and the Danish Psychiatric Central Research Register, whereas suicide death was identified through the Danish Causes of Death Register, through 2016. Flexible parametric and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for suicide attempt and suicide death among spouses of patients with a cancer diagnosis. Results: The study included 409 338 exposed individuals and 2 046 682 unexposed individuals (median [IQR] age at cohort entry for both groups, 63 [54-70] years; 55.4% women). During the follow-up, 2714 incident cases of suicide attempt among exposed individuals (incidence rate [IR], 62.6 per 100 000 person-years) and 9994 among unexposed individuals (IR, 50.5 per 100 000 person-years) were identified, as well as 711 cases of suicide death among the exposed individuals (IR, 16.3 per 100 000 person-years) and 2270 among the unexposed individuals (IR, 11.4 per 100 000 person-years). An increased risk of suicide attempt (HR, 1.28; 95% CI, 1.23-1.34) and suicide death (HR, 1.47; 95% CI, 1.35-1.60) was observed among spouses of patients with cancer throughout the follow-up. The increased risk was particularly notable during the first year after the cancer diagnosis, with an HR of 1.45 (95% CI, 1.27-1.66) for suicide attempt and 2.56 (95% CI, 2.03-3.22) for suicide death. There was a greater risk increase for both suicide attempt and suicide death when the cancer was diagnosed at an advanced stage or when the spouse died after the cancer diagnosis. Conclusions and Relevance: These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.

Mapping the landscape of artificial intelligence in skin cancer research: a bibliometric analysis.

Objective: Artificial intelligence (AI), with its potential to diagnose skin cancer, has the potential to revolutionize future medical and dermatological practices. However, the current knowledge regarding the utilization of AI in skin cancer diagnosis remains somewhat limited, necessitating further research. This study employs visual bibliometric analysis to consolidate and present insights into the evolution and deployment of AI in the context of skin cancer. Through this analysis, we aim to shed light on the research developments, focal areas of interest, and emerging trends within AI and its application to skin cancer diagnosis. Methods: On July 14, 2023, articles and reviews about the application of AI in skin cancer, spanning the years from 1900 to 2023, were selected from the Web of Science Core Collection. Co-authorship, co-citation, and co-occurrence analyses of countries, institutions, authors, references, and keywords within this field were conducted using a combination of tools, including CiteSpace V (version 6.2. R3), VOSviewer (version 1.6.18), SCImago, Microsoft Excel 2019, and R 4.2.3. Results: A total of 512 papers matching the search terms and inclusion/exclusion criteria were published between 1991 and 2023. The United States leads in publications with 149, followed by India with 61. Germany holds eight positions among the top 10 institutions, while the United States has two. The most prevalent journals cited were Cancer, the European Journal of Cancer, and Sensors. The most frequently cited keywords include "skin cancer", "classification", "artificial intelligence", and "deep learning". Conclusions: Research into the application of AI in skin cancer is rapidly expanding, and an increasing number of scholars are dedicating their efforts to this field. With the advancement of AI technology, new opportunities have arisen to enhance the accuracy of skin imaging diagnosis, treatment based on big data, and prognosis prediction. However, at present, the majority of AI research in the field of skin cancer diagnosis is still in the feasibility study stage. It has not yet made significant progress toward practical implementation in clinical settings. To make substantial strides in this field, there is a need to enhance collaboration between countries and institutions. Despite the potential benefits of AI in skin cancer research, numerous challenges remain to be addressed, including developing robust algorithms, resolving data quality issues, and enhancing results interpretability. Consequently, sustained efforts are essential to surmount these obstacles and facilitate the practical application of AI in skin cancer research.

Wavefront aberrations caused by biomechanical effects after Small Incision Lenticule Extraction (SMILE) based on finite element analysis.

To examine wavefront aberrations induced by biomechanical effects after Small Incision Lenticule Extraction (SMILE) surgery. The three-dimensional (3D) finite element models of the human eye were established. By loading the intraocular pressure (IOP), the displacement of the anterior and posterior surface of the cornea was calculated. Then the displacement was converted into the wavefront aberrations by wave-surface fitting. The results showed that the induced wavefront aberrations were noticeable from biomechanical effects after SMILE surgery. The induced higher-order aberrations from the anterior corneal surface included spherical aberration, y-Trefoil, and x-Tetrafoil. Spherical aberration was positively correlated with corrected diopter (D), but x-Tetrafoil and y-Trefoil remained stable. The induced wavefront aberrations from the posterior corneal surface were smaller than those from the anterior corneal surface, and some of the aberrations compensated each other. With IOP increased, defocus and x-Tetrafoil from the anterior corneal surface increased, while y-Trefoil and spherical aberration decreased. The IOP only affected defocus from the posterior corneal surface. In addition, the incision size also had a distinct impact on primary x-astigmatism and x-Trefoil from the anterior corneal surface, and it had a smaller effect on the aberrations from the posterior corneal surface. Therefore, the biomechanical effects increased residual wavefront aberrations after SMILE refractive surgery.

Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort.

Background: Previous studies have examined the link between blood metabolic biomarkers and risk of thyroid cancer, with inconclusive results. We performed a cohort study based on the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) Cohort, including 561,388 individuals undergoing health examinations during 1985−1996 with a follow-up of >30 years. Methods: Newly diagnosed cases of thyroid cancer were identified from the Swedish Cancer Register. We assessed the associations of nine blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolism measured at the time of health examinations with the subsequent risk of thyroid cancer and demonstrated the temporal trend of these biomarkers during the 30 years before diagnosis of thyroid cancer. Results: After multivariable adjustment, there was a lower risk of thyroid cancer, per standard deviation increase in total cholesterol (TC; HR 0.91; 95%CI 0.82−0.99) and HDL-C (HR 0.86; 95%CI 0.75−0.99). During the 20 to 30 years before diagnosis, patients with thyroid cancer, as a group, demonstrated constantly lower levels of TC and HDL-C, compared to controls. Further, patients with thyroid cancer demonstrated declining levels of these biomarkers during the ten years before diagnosis, whereas controls demonstrated stable or increasing levels. Conclusions: Taken together, we found blood levels of TC and HDL-C to be associated with the risk of thyroid cancer and that there was a declining level of metabolic biomarkers during the 10 years before diagnosis of thyroid cancer.

Effect of Panax ginseng and Fructus Mume on Intestinal Barrier and Gut Microbiota in Rats with Diarrhea.

Panax ginseng and Fructus mume (Renshen Wumei in Chinese, RW) are natural medicines with high nutritional and pharmacological value. They have been widely used together in China to treat gastrointestinal diseases, especially persistent diarrhea, but the potential mechanisms remain elusive. In this study, a diarrhea model was established in rats using a 30% aqueous extract of senna. The therapeutic effects of RW were evaluated by recording the prevalence of loose stools, the diarrhea index, and histopathological changes in colon tissue. The levels of mucins, tight junction (TJ) proteins, inflammatory cytokines, and phosphoinositide 3-kinase/Akt/nuclear factor-κB (PI3K/Akt/NF-κB) signaling pathway proteins were measured. Metagenomic sequencing was used to analyze the gut microbiota. Treatment with RW alleviated injury to the intestinal barrier in rats with diarrhea and also upregulated levels of Muc2 and TJ proteins, such as occludin, zonula occludens-1, and claudin-1. Administration of RW regulated the structure of the gut microbiota in diarrheal rats. Furthermore, RW suppressed levels of interleukin (IL), tumor necrosis factor (TNF)-α, IL-1, PI3K, Akt, and p-NF-κB p65 and also increased IL-4 levels. Our study indicates that P. ginseng and Fructus mume help improve the symptoms of diarrhea, possibly by alleviating the intestinal barrier injury, regulating intestinal flora composition, and inhibiting the PI3K/Akt/NF-κB signaling pathway.

Blood metabolic biomarkers and the risk of head and neck cancer: An epidemiological study in the Swedish AMORIS Cohort.

Multiple studies have investigated the role of carbohydrate and lipid metabolism on the risk of head and neck cancer (HNC), with however conflicting results. We performed a study of 561,388 individuals of the Swedish AMORIS Cohort with blood test results on nine biomarkers for carbohydrate, lipid, and apolipoprotein metabolism during 1985-1996. We examined the associations of these biomarkers with the future risk of HNC through 2020 and demonstrated the temporal changes of these biomarkers during the decades before cancer diagnosis. We found that there was a positive association between blood level of glucose, total cholesterol (TC), triglycerides (TG), and Apoprotein A-I (ApoA-I) and the risk of HNC. Per standard deviation increase, the hazard ratio (HR) was 1.05 (95% confidence interval [CI] 1.02-1.09) for glucose, 1.09 (95% CI 1.05-1.13) for TC, 1.13 (95% CI 1.08-1.17) for TG, and 1.11 (95% CI 1.04-1.19) for ApoA-I. The associations were primarily noted for squamous cell carcinoma but not adenocarcinoma. Compared to controls, patients with HNC, primarily squamous cell carcinoma, showed constantly higher levels of glucose, TC, TG, and ApoA-I during the 30 years before diagnosis. In conclusion, findings of the study add new and high-quality evidence to the early involvement of carbohydrate and lipid metabolism in the oncogenesis of human cancer.