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Background: Currently, the standard treatment for renal pelvis carcinoma is radical nephroureterectomy with bladder cuff excision. To describe the feasibility of retroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping for cancer of renal pelvis, we report this special case for the first time.Case Presentation: A 67-year-old woman received this operation. Preoperative ureteroscopy revealed a papillary neoplasm with a pedicle in the upper calyx of the left kidney. After entering the retroperitoneal space and dissociating the renal artery and renal vein, the target artery was clamped beyond the final bifurcation before entering the parenchyma. After incision of the left renal parenchyma and exposure of the upper calyceal neck, the tumor was found confined to the upper calyx. Thereafter, the renal calyx and parenchyma were sutured successively after complete resection of the neoplasm. Postoperative pathological examination confirmed that the Grade I papillary carcinoma was confined to the mucosal layer. Thus far, there is no evidence of recurrence during the follow-up period for more than 42 months after surgery.Conclusions: Retroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping of the kidney provides a feasible treatment modality for noninvasive tumors that are limited to the calyx. [ABSTRACT FROM AUTHOR]

Backgroud: Choroidal detachment (CD) following primary rhegmatogenous retinal detachment (RRD) is a special type of RRD. The purpose of this study is to investigate the potential risk factors of RRD with CD in a Chinese population.Methods: All of 201 consecutive RRD with CD patients and 210 RRD without CD patients were enrolled in this case-control retrospective study. The clinical data from these cases were reviewed here. Patients were undergone scleral buckling or encircling or both, or pars plana vitrectomy with or without scleral buckling or encircling or both according the patients' condition. The incidence of RRD with CD in this Chinese population was measured, and the potential risk factors for the development of RRD with CD were investigated by multivariate logistic regression analysis.Results: In this population, the incidence of RRD with CD was 8.6 %. The incidence of RRD with CD was significantly higher in patients with macular hole (P < 0.05), retinal breaks located posterior to the equator (P < 0.05), and total detachment (P < 0.05). Furthermore, the incidence of RRD with CD was significantly higher in patients with longer axial length (P < 0.05) only when ages, IOP, AL and duration time was set for categorical variables.Conclusions: Hypotony, retinal breaks located posteriorly especially macular hole, longer axial length, and the whole retinal detachment might be the potential risk factors for the development of CD in RRD patients. [ABSTRACT FROM AUTHOR]

The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA). First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg−1·d−1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis. The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice. The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level. • The HUA model mice showed intestinal barrier damage. • NaB reversed the damage of intestinal barrier in HUA model mice. • NaB reduces serum UA level in HUA model mice. • NaB may reduce the serum UA level of HUA model mice by up-regulating the expression level of intestinal ABCG2 protein. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are aromatic compounds with two or more benzene rings composed of carbon and hydrogen, which are potential hazard substances produced by food thermal processing. However, the toxicological effects differ due to their varieties, causing many countries to have inconsistent standards. Also, the formation mechanism of PAHs in meat products is still controversial, and the detection methods and influencing factors are diverse, resulting in food control challenges. Therefore, this work reviewed PAHs in food, especially meat products from the perspectives of their classification, toxicological evaluation, formation mechanism, methods for extraction and detection, influencing factors, and control strategies. This paper provides some perspectives on the control of food PAHs in research and industrial production. [ABSTRACT FROM AUTHOR]

Thiophene-based monohelicene ( TS[7]H ), triple helicenes ( TT[7]H ), and hexapole helicenes ( TH[7]H ) were synthesized via oxidative photocyclization and cascade Suzuki/intramolecular cyclization as the crucial steps. The enantiomers of TS[7]H , TT[7]H-2 , and TH[7]H exhibited circularly polarized luminescence (CPL), and the luminescence dissymmetry factors ( g lum ) gradually increased from -5.1 × 10 -4 to -2.0 × 10 -3 with an increase in multiplicity from TS[7]H to TH[7]H . In addition, TS[7]H , TT[7]H , and TH[7]H displayed a second-level long afterglow at 77 K.

Purpose: To evaluate the clinical and retinal imaging features of Chinese patients with acute macular neuroretinopathy (AMN) associated with COVID-19., Design: A prospective observational study., Methods: Retinal imaging, including color fundus photography, near-infrared imaging (NIR), swept-source optical coherence tomography (SS-OCT), optical coherence tomography angiography (OCTA), and Humphrey perimetry, were conducted for each case., Results: All cases were included within the first three months following the pandemic outbreak. A total of 12 male patients (36.36 %) and 21 female patients (63.64 %) were prospectively recruited, and 29 cases (87.88 %) were bilaterally affected. The median interval between the onset of fever and the appearance of ocular symptoms was two days (range, 0.5-5.0 days). Apart from the outer retinal changes typical of AMN, changes in the inner retinal layers were observed, including intraretinal hemorrhage (8.06 %), cotton wool spots (9.68 %), and paracentral acute middle maculopathy (PAMM) (8.06 %). Smaller retinal inner nuclear layer hyperreflective speckles (RIHS) (41.94 %) were identified as a distinguishing feature from typical PAMM. Voids of vessel signals were found in the superficial (11.54 %), intermediate (82.69 %), and deep capillary plexus (98.08 %), and in the choriocapillaris (19.23 %) on OCTA. Humphrey perimetry illustrated central, paracentral, and peripheral scotomas. The occult lesions associated with AMN, PAMM, and some of the RIHS illustrated by OCT were visualized topographically and further confirmed by OCTA as perfusion defects., Conclusion: An increase in AMN cases correlated with the SARS-CoV-2 outbreak. Additional features, including widespread inner retinal perfusion deficits, were observed and may serve as potential biomarkers for systemic microcirculation dysregulation in COVID-19., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the preference of primary HCWs and residents on vaccination consultation in community health services to provide evidence for vaccine hesitancy intervention strategies., Methods: A discrete choice model (DCM) was constructed to evaluate the preference difference between primary HCWs and residents on vaccination consultation in community health services in China during May-July 2022., Results: A total of 282 residents and 204 HCWs were enrolled in this study. The residents preferred consulting with an HCW-led approach (β = 2.168), with specialized content (β = 0.954), and accompanied by telephone follow-up (β = 1.552). In contrast, the HCWs preferred face-to-face consultation (β = 0.540) with an HCW-led approach (β = 0.458) and specialized content (β = 0.409), accompanied by telephone follow-up (β = 0.831). College residents and residents with underlying self-reported disease may be near-critically inclined to choose traditional consultation (an offline, face-to-face consultation with standardized content and more prolonged duration) rather than a new-media consulting group (an online consultation with specialized content within 5 min). Urban HCWs preferred long-term consultation groups (the resident-led offline consultation with follow-up lasting more than 5 min). In contrast, rural HCWs preferred efficient consultation (the HCW-led, short-duration, standardized offline consultation mode)., Conclusion: The selection preference for vaccine consultation reveals a gap between providers and demanders, with different groups exhibiting distinct preferences. Identifying these targeted gaps can help design more acceptable and efficient interventions, increasing their likelihood of success and leading to better resource allocation for policymakers to develop targeted vaccination policies.

Objective: To estimate whether genetically proxied periodontitis causally impacts the brain cortical structure using Mendelian randomization (MR)., Background: Periodontitis is one of the most prevalent inflammatory conditions globally, and emerging evidence has indicated its influences on distal organs, including the brain, whose disorders are always accompanied by magnetic resonance imaging (MRI)-identified brain cortical changes. However, to date, no available evidence has revealed the association between periodontitis and brain cortical structures., Methods: The instrumental variables (IVs) were adopted from previous genome-wide association study (GWAS) studies and meta-analyses of GWAS studies of periodontitis from 1844 to 5266 cases and 8255 to 12 515 controls. IVs were linked to GWAS summary data of 51 665 patients from the ENIGMA Consortium, assessing the impacts of genetically proxied periodontitis on the surficial area (SA) or the cortical thickness (TH) of the global and 34 MRI-identified functional regions of the brain. Inverse-variance weighted was used as the primary estimate; the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy., Results: Genetically proxied periodontitis affects the SA of the medial orbitofrontal cortex, the lateral orbitofrontal cortex, the inferior temporal cortex, the entorhinal cortex, and the temporal pole, as well as the TH of the entorhinal. No pleiotropy was detected., Conclusions: Periodontitis causally influences the brain cortical structures, implying the existence of a periodontal tissue-brain axis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Dental caries is one of the most prevalent oral diseases and causes of tooth loss. Cross-sectional studies observed epidemiological associations between dental caries and brain degeneration disorders, while it is unknown whether dental caries causally affect the cerebral structures. This study tested whether genetically proxied DMFS (the sum of Decayed, Missing, and Filled tooth Surfaces) causally impacts the brain cortical structure using Mendelian randomization (MR)., Methods: The summary-level GWAS meta-analysis data from the GLIDE consortium were used for DMFS, including 26,792 participants. ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) consortium GWAS summary data of 51,665 patients were used for brain structure. This study estimated the causal effects of DMFS on the surface area (SA) and thickness (TH) of the global cortex and functional cortical regions accessed by magnetic resonance imaging (MRI). Inverse-variance weighted (IVW) was used as the primary estimate, the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy., Results: Genetically proxied DMFS decreases the TH of the banks of the superior temporal sulcus (BANSSTS) with or without global weighted (weighted, β = - 0.0277 mm, 95% CI: - 0.0470 mm to - 0.0085 mm, P = 0.0047; unweighted, β = - 0.0311 mm, 95% CI: - 0.0609 mm to - 0.0012 mm, P = 0.0412). The causal associations were robust in various sensitivity analyses., Conclusions: Dental caries causally decrease the cerebral cortical thickness of the BANKSSTS, a cerebral cortical region crucial for language-related functions, and is the most affected brain region in Alzheimer's disease. This investigation provides the first evidence that dental caries causally affects brain structure, proving the existence of teeth-brain axes. This study also suggested that clinicians should highlight the causal effects of dental caries on brain disorders during the diagnosis and treatments, the cortical thickness of BANKSSTS is a promising diagnostic measurement for dental caries-related brain degeneration., (© 2024. The Author(s).)

Maleimide chemistry is widely used in antibody-drug conjugate (ADC) generation to connect drugs to antibodies through a succinimide linker. The resulting ADC is prone to payload loss via a reverse Michael reaction, leading to premature drug release in vivo . Complete succinimide hydrolysis is an effective strategy to overcome the instability of ADC. However, we discovered through previous work that hydrolysed succinimide rings can close again in a liquid formulation during storage and under thermal stress conditions. In this work, a set of maleimide linkers with hydrolysis-prone groups were designed. The corresponding ADCs were prepared and subjected to thermal stress conditions. The extent of succinimide hydrolysis and drug release was measured, and ADC properties such as SEC, DAR, pI and clog  P of linkers were calculated. Our results demonstrated that even though all these groups increased the hydrolysis rate, they have different impacts on maintaining the hydrolysed succinimide ring in an open conformation and ADC stability in a liquid formulation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chimeric antigen receptor T cell (CAR-T) therapies show considerable clinical efficacy in patients with B cell malignancies, but their efficacy is limited in patients with T cell acute lymphoblastic leukemia (T-ALL). CD5 is expressed on ∼85 % of malignant T cells, and CD5-targeting CAR-T cells can exhibit potent antitumor activity against T-ALL. However, optimization of CAR costimulatory endo-, hinge, and transmembrane domains could further increase their expansion and persistence, thereby enhancing their efficacy following exposure to tumor cells. Here we designed CD5-specific CARs with different molecular structures to generate CAR-T cells and investigated their anti-tumor efficacy in vitro and in vivo. CD5 CARs with a 4-1BB costimulatory domain (BB.z) or a CD28 costimulatory domain (28.z) exhibited specific cytotoxicity against CD5 + malignant cells in vitro. However, both failed to prolong the survival of T-ALL xenograft mice. Subsequently, we substituted the 28.z CAR hinge region with C H 2C H 3, which enhanced the ability of C H 2C H 3-CD5 CAR-T cells to specifically eradicate T-ALL cells in vitro and in vivo. Furthermore, patient-derived C H 2C H 3-CD5 CAR-T cells were generated which showed a marked killing effect of CD5-positive acute T-ALL cells in vitro. The anti-tumor activity of CD5 CAR-T cells with a CD28 co-stimulation domain and C H 2C H 3 hinge region was superior to those with BB.z and 28.z domains. These preclinical data provided new insights into the factors dictating efficacy in T-ALL treatment with CAR-T cells and hold promise for clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Systemic inflammatory response syndrome (SIRS), at least in part driven by necroptosis, is characterized by life-threatening multiple organ failure. Blocking the progression of SIRS and consequent multiple organ dysfunction is challenging. Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is an important cell death and inflammatory mediator, making it a potential treatment target in several diseases. Here, using a drug repurposing approach, we show that inhibiting RIPK1 is also an effective treatment for SIRS. We performed cell-based high-throughput drug screening of an US Food and Drug Administration (FDA)-approved drug library that contains 1953 drugs to identify effective inhibitors of necroptotic cell death by SYTOX green staining. Dose-response validation of the top candidate, quizartinib, was conducted in two cell lines of HT-22 and MEFs. The effect of quizartinib on necroptosis-related proteins was evaluated using western blotting, immunoprecipitation, and an in vitro RIPK1 kinase assay. The in vivo effects of quizartinib were assessed in a murine tumor necrosis factor α (TNFα)-induced SIRS model. High-throughput screening identified quizartinib as the top "hit" in the compound library that rescued cells from necroptosis in vitro. Quizartinib inhibited necroptosis by directly inhibiting RIPK1 kinase activity and blocking downstream complex IIb formation. Furthermore, quizartinib protected mice against TNFα-induced SIRS. Quizartinib, as an FDA-approved drug with proven safety and efficacy, was repurposed for targeted inhibition of RIPK1. This work provides essential preclinical data for transferring quizartinib to the treatment of RIPK1-dependent necroptosis-induced inflammatory diseases, including SIRS., (© 2023 Federation of American Societies for Experimental Biology.)

High-risk neuroblastoma exhibits transcriptional activation of the mevalonate pathway that produces cholesterol and nonsterol isoprenoids. A better understanding of how this metabolic reprogramming contributes to neuroblastoma development could help identify potential prevention and treatment strategies. Here, we report that both the cholesterol and nonsterol geranylgeranyl-pyrophosphate branches of the mevalonate pathway are critical to sustain neuroblastoma cell growth. Blocking the mevalonate pathway by simvastatin, a cholesterol-lowering drug, impeded neuroblastoma growth in neuroblastoma cell line xenograft, patient-derived xenograft (PDX), and TH-MYCN transgenic mouse models. Transcriptional profiling revealed that the mevalonate pathway was required to maintain the FOXM1-mediated transcriptional program that drives mitosis. High FOXM1 expression contributed to statin resistance and led to a therapeutic vulnerability to the combination of simvastatin and FOXM1 inhibition. Furthermore, caffeine synergized with simvastatin to inhibit the growth of neuroblastoma cells and PDX tumors by blocking statin-induced feedback activation of the mevalonate pathway. This function of caffeine depended on its activity as an adenosine receptor antagonist, and the A2A adenosine receptor antagonist istradefylline, an add-on drug for Parkinson's disease, could recapitulate the synergistic effect of caffeine with simvastatin. This study reveals that the FOXM1-mediated mitotic program is a molecular statin target in cancer and identifies classes of agents for maximizing the therapeutic efficacy of statins, with implications for treatment of high-risk neuroblastoma., Significance: Caffeine treatment and FOXM1 inhibition can both enhance the antitumor effect of statins by blocking the molecular and metabolic processes that confer statin resistance, indicating potential combination therapeutic strategies for neuroblastoma. See related commentary by Stouth et al., p. 2091., (©2023 The Authors; Published by the American Association for Cancer Research.)

Leonurine (Leo) is a natural alkaloid isolated from the herb Leonurus japonicus Houtt. (Leonuri) that has been shown to inhibit oxidative stress and inflammation. However, the role and mechanism of Leo in acetaminophen (APAP)-induced acute liver injury (ALI) remain unknown. In this study, we investigated the protective effect of Leo against APAP-induced ALI and elucidated the molecular mechanism. Here, we showed that the damage to mouse primary hepatocytes (MPHs) induced by APAP was attenuated by treatment with Leo, which promoted proliferation and inhibited oxidative stress injury, and Leo significantly improved APAP-induced ALI in mice. Leo could protect against APAP-induced ALI by reducing serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, hepatic histopathological damage, liver cell necrosis, inflammation, and oxidative stress-induced damage in vivo and in vitro. Moreover, the results indicated that Leo relieved APAP-induced liver cell necrosis by reducing the expression of Bax and cleaved caspase-3 and increasing Bcl-2 expression. Leo alleviated APAP-induced oxidative stress-induced damage by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which facilitated Nrf2 nuclear translocation and upregulated oxidative stress-related protein expression in liver tissues. Moreover, the results suggested that APAP-induced inflammation in the liver was suppressed by Leo by suppressing the Toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3) pathways. In addition, Leo facilitated the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in the liver tissue of ALI mice. Network pharmacology, molecular docking, and western blotting showed that PI3K was a potential target of Leo in the treatment of ALI. Molecular docking and cellular thermal shift assay (CETSA) indicated that Leo could stably bind to the PI3K protein. In conclusion, Leo attenuated ALI, and reversed liver cell necrosis, the inflammatory response and oxidative stress-induced damage by regulating the PI3K/AKT signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function. These events include inter-cell communication, cell proliferation, cell migration, extracellular matrix differentiation, and other critical biological processes. Glycosylation is the crucial conservative and universal post-translational modification in all eukaryotic cells [1], with influential roles in intercellular recognition, regulation, signaling, immune response, cellular transformation, and disease development. Studies have shown that abnormally glycosylation of proteins is a well-recognized feature of cancer cells, and specific glycan structures are considered markers of tumor development. There are many studies on gene expression and regulation during tissue repair and regeneration. Still, there needs to be more knowledge of complex carbohydrates' effects on tissue repair and regeneration, such as glycosylation. Here, we present a review of studies investigating protein glycosylation in the tissue repair and regeneration process., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(1) Background: To explore the influencing factors of human papillomavirus (HPV) vaccination among mothers and daughters so as to provide evidence and strategies for improving the HPV vaccination rate of 9-18-years-old girls. (2) A questionnaire survey was conducted among the mothers of 9-18-year-old girls from June to August 2022. The participants were divided into the mother and daughter vaccinated group (M1D1), the mother-only vaccinated group (M1D0), and the unvaccinated group (M0D0). Univariate tests, the logistic regression model, and the Health Belief Model (HBM) were employed to explore the influencing factors. (3) Results: A total of 3004 valid questionnaires were collected. According to the regions, Totally 102, 204, and 408 mothers and daughters were selected from the M1D1, M1D0, and M0D0 groups, respectively. The mother having given her daughter sex education (OR = 3.64; 95%CI 1.70, 7.80), the mother's high perception of disease severity (OR = 1.79; 95%CI 1.02, 3.17), and the mother's high level of trust in formal information (OR = 2.18; 95%CI 1.26, 3.78) were all protective factors for both the mother and her daughter's vaccination. The mother's rural residence (OR = 0.51; 95%CI 0.28, 0.92) was a risk factor for vaccination of both mother and daughter. The mother's education of high school or above (OR = 2.12; 95%CI 1.06, 4.22), the mother's high level of HPV and HPV vaccine knowledge (OR = 1.72; 95%CI 1.14, 2.58), and the mother's high level of trust in formal information (OR = 1.72; 95%CI 1.15, 2.57) were protective factors of mother-only vaccination. The older the mother (OR = 0.95; 95%CI 0.91, 0.99) was classed as a risk factor for mother-only vaccination. "Waiting until the daughters are older to receive the 9-valent vaccine" is the main reason why the daughters of M1D0 and M0D0 are not vaccinated". (4) Chinese mothers had a high willingness to vaccinate their daughters with the HPV vaccine. The higher education level of the mother, giving sex education to the daughter, the older ages of mothers and daughters, the mother's high level of HPV and HPV vaccine knowledge, a high level of perception of the disease severity, and a high level of trust in formal information were promoting factors of HPV vaccination for mother and daughter, and rural residence was a risk factor to vaccination. To promote HPV vaccination in girls from 9-18 years old, communities could provide health education to rural mothers with low education levels; the government could advocate for HPV vaccination through issuing policy documents; and doctors and the CDC could popularize the optimal age for HPV vaccination to encourage mothers to vaccinate their daughters at the age of 9-14 years old.

Purpose: To observe the characteristics of highly myopic macular holes (HMMHs) with macular retinoschisis (MRS) by optical coherence tomography (OCT) and explore the possible relationship between HMMHs and different types of MRS., Methods: We consecutively reviewed the clinical data and OCT images of the patients with HMMHs from June 2015 to February 2021. Then we picked eyes with MRS from these HMMHs for analysis. The minimum linear diameter (MLD), basal diameter (BD), and height (H) of HMMHs were measured. HMMHs were grouped according to the extent or layer involvement of the concomitant MRS and the characteristics were compared among groups. The impact of MRS on the MLD of macular hole was analyzed with multivariable linear regression., Results: We included 127 patients with MRS from 168 HMMHs (75.5%) for analysis. According to the different classification systems, the most frequent type of MRS in HMMHs was S3 (foveal but not entire macular area MRS) (62.2%) and both inner- and outer- (I/O-MRS) involved types. In our study, HMMHs with more extensive MRS had larger MLD, larger BD, larger H, and poorer best-corrected visual acuity (BCVA). Meanwhile, HMMHs with outer layer-involved MRS (outer MRS and I/O-MRS) had larger BD than HMMH with only inner layer-involved MRS. (All P < 0.05) Multivariable linear regression further illustrated only the extent of MRS was significantly associated with the MLD of HMMH, while there was no significant correlation between the involved retinal layers and the MLD of HMMH., Conclusion: HMMH with MRS presented as a predominant type in HMMHs. The MRS was always with a relatively large extent and involved both inner and outer layers. MLD of HMMH was mainly affected by the extent of MRS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Becker muscular dystrophy (BMD) is a genetic and progressive neuromuscular disease caused by mutations in the dystrophin gene with no available cure. A case report and comprehensive review of BMD cases aim to provide important clues for early diagnosis and implications for clinical practice. Genes and pathways identified from microarray data of muscle samples from patients with BMD help uncover the potential mechanism and provide novel therapeutic targets for dystrophin-deficient muscular dystrophies., Methods: We describe a BMD family with a 10-year-old boy as the proband and reviewed BMD cases from PubMed. Datasets from the Gene Expression Omnibus database were downloaded and integrated with the online software., Results: The systematic review revealed the clinical manifestations and mutation points of the dystrophin gene. Gene ontology analysis showed that extracellular matrix organization and extracellular structure organization with enrichment of upregulated genes coexist in three datasets. We present the first report of TUBA1A involvement in the development of BMD/Duchenne muscular dystrophy (DMD)., Discussion: This study provides important implications for clinical practice, uncovering the potential mechanism of the progress of BMD/DMD, and provided new therapeutic targets., (© 2021. Fondazione Società Italiana di Neurologia.)

Metabolic reprogramming is an integral part of the growth-promoting program driven by the MYC family of oncogenes. However, this reprogramming also imposes metabolic dependencies that could be exploited therapeutically. Here we report that the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is an attractive therapeutic target for MYCN-amplified neuroblastoma, a childhood cancer with poor prognosis. Gene expression profiling and metabolomic analysis reveal that MYCN promotes pyrimidine nucleotide production by transcriptional upregulation of DHODH and other enzymes of the pyrimidine-synthesis pathway. Genetic and pharmacological inhibition of DHODH suppresses the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines. Furthermore, we obtain evidence suggesting that serum uridine is a key factor in determining the efficacy of therapeutic agents that target DHODH. In the presence of physiological concentrations of uridine, neuroblastoma cell lines are highly resistant to DHODH inhibition. This uridine-dependent resistance to DHODH inhibitors can be abrogated by dipyridamole, an FDA-approved drug that blocks nucleoside transport. Importantly, dipyridamole synergizes with DHODH inhibition to suppress neuroblastoma growth in animal models. These findings suggest that a combination of targeting DHODH and nucleoside transport is a promising strategy to overcome intrinsic resistance to DHODH-based cancer therapeutics., (© 2021. The Author(s).)

Mitochondria and chloroplast are very important organelles for organism, participating in basic life activity. Their genomes contain many repeats which can lead to a variation of genome structure. Oryza is an important genus for human beings' nutrition. Several mitochondrial and chloroplast genomes of Oryza have been sequenced, which help us to insight the distribution and evolution of the repeats in Oryza species. In this paper, we compared six mitochondrial and 13 chloroplast genomes of Oryza and found that the structures of mitochondrial genomes were more diverse than chloroplast genomes. Since repeats can change the structure of the genome, resulting in the structural diversity of the genome, we analyzed all repeats and found 31 repeats in mitochondrial and 13 repeats in chloroplast genomes. Further, we developed 21 pairs of MRS molecular markers and 12 pairs of CRS molecular markers based on mitochondrial repeats and chloroplast repeats, respectively. These molecular markers can be used to detect the repeat-mediated recombination in Oryza mitochondrial and chloroplast genomes by PCR or fluorescence quantification., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-020-01198-6., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interests., (© The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature 2021.)

Background: Several studies have investigated miR-4293 rs12220909 polymorphisms and cancer susceptibility and yielded different results. Because of this controversy, we designed a meta-analysis to assess comprehensively the association of the rs12220909 polymorphism with cancer risk., Methods: Relevant articles were collected by searching the databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang. Data on rs12220909 in cancer patients and controls were extracted. Sensitivity analyses and publication bias assessments were performed., Results: Five studies with 3820 cases and 4574 controls were included in our meta-analysis. Pooled analyses showed that the rs12220909 polymorphism was not associated with cancer risk in any genetic model. (C vs G: odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.74-1.07; GC vs GG: OR = 0.83, 95% CI = 0.67-1.03; CC vs GG: OR = 1.06, 95% CI = 0.82-1.36; CC+GC vs GG: OR = 0.84, 95% CI = 0.69-1.03; CC vs GC+GG: OR = 1.10, 95% CI = 0.85-1.40)., Conclusions: Our results indicate that rs12220909 is not associated with cancer risk. Larger, well-designed multicenter studies are needed to further explore the association of miR-4293 rs12220909 polymorphism with cancer risk.

Genomic amplification of the oncogene MYCN is a major driver in the development of high-risk neuroblastoma, a pediatric cancer with poor prognosis. Given the challenge in targeting MYCN directly for therapy, we sought to identify MYCN-dependent metabolic vulnerabilities that can be targeted therapeutically. Here, we report that the gene encoding glycine decarboxylase (GLDC), which catalyzes the first and rate-limiting step in glycine breakdown with the production of the one-carbon unit 5,10-methylene-tetrahydrofolate, is a direct transcriptional target of MYCN. As a result, GLDC expression is markedly elevated in MYCN-amplified neuroblastoma tumors and cell lines. This transcriptional upregulation of GLDC expression is of functional significance, as GLDC depletion by RNA interference inhibits the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines by inducing G1 arrest. Metabolomic profiling reveals that GLDC knockdown disrupts purine and central carbon metabolism and reduces citrate production, leading to a decrease in the steady-state levels of cholesterol and fatty acids. Moreover, blocking purine or cholesterol synthesis recapitulates the growth-inhibitory effect of GLDC knockdown. These findings reveal a critical role of GLDC in sustaining the proliferation of neuroblastoma cells with high-level GLDC expression and suggest that MYCN amplification is a biomarker for GLDC-based therapeutic strategies against high-risk neuroblastoma.

MYCN amplification drives the development of neuronal cancers in children and adults. Given the challenge in therapeutically targeting MYCN directly, we searched for MYCN-activated metabolic pathways as potential drug targets. Here we report that neuroblastoma cells with MYCN amplification show increased transcriptional activation of the serine-glycine-one-carbon (SGOC) biosynthetic pathway and an increased dependence on this pathway for supplying glucose-derived carbon for serine and glycine synthesis. Small molecule inhibitors that block this metabolic pathway exhibit selective cytotoxicity to MYCN -amplified cell lines and xenografts by inducing metabolic stress and autophagy. Transcriptional activation of the SGOC pathway in MYCN -amplified cells requires both MYCN and ATF4, which form a positive feedback loop, with MYCN activation of ATF4 mRNA expression and ATF4 stabilization of MYCN protein by antagonizing FBXW7-mediated MYCN ubiquitination. Collectively, these findings suggest a coupled relationship between metabolic reprogramming and increased sensitivity to metabolic stress, which could be exploited as a strategy for selective cancer therapy. SIGNIFICANCE: This study identifies a MYCN-dependent metabolic vulnerability and suggests a coupled relationship between metabolic reprogramming and increased sensitivity to metabolic stress, which could be exploited for cancer therapy. See related commentary by Rodriguez Garcia and Arsenian-Henriksson, p. 3818 ., (©2019 American Association for Cancer Research.)

CD4 + CD25 + regulatory T (Treg) cells maintain the function of immune tolerance and the balance of immune cells. Defects in the number and function of Treg cells can induce the development and progression of inflammatory disease. Shikonin, the main active ingredient of Lithospermum, has anti-inflammatory and anti-tumor effects. Shikonin is also an effective drug for the treatment of psoriasis, which is a chronic inflammatory skin disease. However, the underlying mechanism is not yet clear. To evaluate the role of shikonin on the induction of Treg cells, we tested the number and function of Treg cells in vivo and in vitro. Shikonin can effectively promote the differentiation of iTreg cells by inhibiting the AKT/mTOR pathway in vitro. Moreover, in vivo, intragastrically administered shikonin effectively improved lesions in mice with imiquimod-induced psoriasis and increased the number of iTreg cells in the spleen and their secretion. Shikonin significantly increases the expression of Foxp3mRNA in skin of the psorisic mice. Therefore, we expect that shikonin can prevent the development of inflammation and treat psoriasis by regulating iTreg cells. Novel ideas for the treatment of psoriasis are also proposed.

Glutaminase-1 (GLS1) is a mitochondrial enzyme found in endothelial cells (ECs) that metabolizes glutamine to glutamate and ammonia. Although glutaminolysis modulates the function of human umbilical vein ECs, it is not known whether these findings extend to human ECs beyond the fetal circulation. Furthermore, the molecular mechanism by which GLS1 regulates EC function is not defined. In this study, we show that the absence of glutamine in the culture media or the inhibition of GLS1 activity or expression blocked the proliferation and migration of ECs derived from the human umbilical vein, the human aorta, and the human microvasculature. GLS1 inhibition arrested ECs in the G 0 /G 1 phase of the cell cycle and this was associated with a significant decline in cyclin A expression. Restoration of cyclin A expression via adenoviral-mediated gene transfer improved the proliferative, but not the migratory, response of GLS1-inhibited ECs. Glutamine deprivation or GLS1 inhibition also stimulated the production of reactive oxygen species and this was associated with a marked decline in heme oxygenase-1 (HO-1) expression. GLS1 inhibition also sensitized ECs to the cytotoxic effect of hydrogen peroxide and this was prevented by the overexpression of HO-1. In conclusion, the metabolism of glutamine by GLS1 promotes human EC proliferation, migration, and survival irrespective of the vascular source. While cyclin A contributes to the proliferative action of GLS1, HO-1 mediates its pro-survival effect. These results identify GLS1 as a promising therapeutic target in treating diseases associated with aberrant EC proliferation, migration, and viability., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Goals: Over the past twenty years, the existence of oral Helicobacter pylori (H. pylori) infection has been controversial and is still disputed. It proposes that living H. pylori do not exist in the oral cavity. However, the progressive loss of efficacy of standard eradication therapies has made the treatment of H. pylori more challenging than ever due to oral H. pylori infection. We conducted a study to explore the existence of oral H. pylori infection among 4321 adults., Procedures: A total 4321 adults (age range, 20-89 years old) comprising 2849 men and 1472 women were recruited by annual physical exam and evaluated using the saliva H. pylori antigen test (HPS) to diagnose oral H. pylori infection and the urea breath test (UBT) to diagnose stomach H. pylori infection. According to the classification on age grouping of World Health Organization, patients were divided into three age groups: A group, the young age subgroup (<45 years); B group, the middle age subgroup (45 to 59 years); C group, the old age subgroup (60-74 years) and D group, the elder subgroup (75-89 years)., Results: We found the positive rate of oral H. pylori was 59.59% in the 95% confidence interval (CI) ranges on A group. The lowest positive rate of H. pylori in D group was 25.48% in the 95% confidence interval CI ranges. There was a statistically significant difference ( p <0.001) between A, B, C, and D groups but no significant difference between men and women., Conclusion: HPS could identify oral H. pylori infection of individuals who have no risk for H. pylori gastric infection. The positive rate of oral H. pylori was 59.59% and this varies across different age groups. This information was not provided by UBT methods. It further identified that the prevalence of oral H. pylori infection is lower in the elder group that may be associated with fewer number of teeth., (© 2017 by the Association of Clinical Scientists, Inc.)

Background: Some previous studies have investigated the relationship between insulin-like growth factor-binding protein-3 polymorphism and prostate cancer (PCa) susceptibility; however, the findings from those studies remain inconsistent. Hence, the aim of this meta-analysis was to provide a more reliable conclusion about such associations., Methods: A meta-analysis based on twelve studies was conducted, and 8,341 PCa cases and 7,734 controls were included in this analysis. All relevant studies published till February 1, 2016, were identified by searching the databases such as PubMed, EMBASE, and Web of Science. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) in order to assess the strength of such associations. Publication bias was evaluated using Begg's funnel plots and Egger's regression test., Results: Several articles provided data only for particular genotypes; therefore, only dominant model analyses were carried out for all of these studies. Initially, the results from this analysis indicated that rs2854744 was not associated with PCa susceptibility (OR=1.12, 95% CI=0.996-1.2). However, after excluding one study due to its heterogeneity and publication bias, a significant relationship was detected between rs2854744 and PCa risk (OR=1.10, 95% CI=1.03-1.17). When stratified by genotyping method, significant results were detected only in the Sequenom method group (OR=1.13, 95% CI=1.04-1.22). Moreover, the results from a subgroup analysis that was conducted by using source of controls were significant only in the population-based control group., Conclusion: This meta-analysis suggested that the insulin-like growth factor-binding protein-3 polymorphism-202 A/C was associated with PCa susceptibility.

Background: With the increasing popularity of cosmetic facial filler injections in recent years, more and more associated complications have been reported. However, the causative surgical procedures and preventative measures have not been studied well up to now. The aim of this stady was to investigate the clinical characteristics and visual prognosis of fundus artery occlusion resulting from cosmetic facial filler injections., Methods: Thirteen consecutive patients with fundus artery occlusion caused by facial filler injections were included. Main outcome measures were filler materials, injection sites, best-corrected visual acuity (BCVA), fundus fluorescein angiography, and associated ocular and systemic manifestations., Results: Eleven patients had ophthalmic artery occlusion (OAO) and one patient each had central retinal artery occlusion (CRAO) and anterior ischemic optic neuropathy (AION). Injected materials included autologous fat (seven cases), hyaluronic acid (five cases), and bone collagen (one case). Injection sites were the frontal area (five cases), periocular area (two cases), temple area (two cases), and nose area and nasal area (4 cases). Injected autologous fat was associated with worse final BCVA than hyaluronic acid. The BCVA of seven patients with autologous fat injection in frontal area and temple area was no light perception. Most of the patients with OAO had ocular pain, headache, ptosis, ophthalmoplegia, and no improvement in final BCVA., Conclusions: Cosmetic facial injections can cause fundus artery occlusion. Autologous fat injection tends to be associated with painful blindness, ptosis, ophthalmoplegia, and poor visual outcomes. The prognosis is much worse with autologous fat injection than hyaluronic acid injection.