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Metabolic disturbance, particularly of glucose metabolism, is a hallmark of tumors such as non-small cell lung cancer (NSCLC). Cancer cells tend to reprogram a majority of glucose metabolism reactions into glycolysis, even in oxygen-rich environments. Although glycolysis is not an efficient means of ATP production compared to oxidative phosphorylation, the inhibition of tumor glycolysis directly impedes cell survival and growth. This review focuses on research advances in glycolysis in NSCLC and systematically provides an overview of the key enzymes, biomarkers, non-coding RNAs, and signaling pathways that modulate the glycolysis process and, consequently, tumor growth and metastasis in NSCLC. Current medications, therapeutic approaches, and natural products that affect glycolysis in NSCLC are also summarized. We found that the identification of appropriate targets and biomarkers in glycolysis, specifically for NSCLC treatment, is still a challenge at present. However, LDHB, PDK1, MCT2, GLUT1, and PFKM might be promising targets in the treatment of NSCLC or its specific subtypes, and DPPA4, NQO1, GAPDH/MT-CO1, PGC-1α, OTUB2, ISLR, Barx2, OTUB2, and RFP180 might be prognostic predictors of NSCLC. In addition, natural products may serve as promising therapeutic approaches targeting multiple steps in glycolysis metabolism, since natural products always present multi-target properties. The development of metabolic intervention that targets glycolysis, alone or in combination with current therapy, is a potential therapeutic approach in NSCLC treatment. The aim of this review is to describe research patterns and interests concerning the metabolic treatment of NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Fu, Zhang, Zhang, Ma, Tang, Zhang and Zhou.)

Tetrabromobisphenol (TBBPA) is the most widely used brominated flame retardant in the world and displays toxicity to humans and animals. However, few studies have focused on its impact on oocyte maturation. Here, TBBPA was added to the culture medium of bovine cumulus-oocyte complexes (COCs) to examine its effect on oocytes. We found that TBBPA exposure displayed an adverse influence on oocyte maturation and subsequent embryonic development. The results of this study showed that TBBPA exposure induced oocyte meiotic failure by disturbing the polar-body extrusion of oocytes and the expansion of cumulus cells. We further found that TBBPA exposure led to defective spindle assembly and chromosome alignment. Meanwhile, TBBPA induced oxidative stress and early apoptosis by mediating the expression of superoxide dismutase 2 (SOD2). TBBPA exposure also caused mitochondrial dysfunction, displaying a decrease in mitochondrial membrane potential, mitochondrial content, mtDNA copy number, and ATP levels, which are regulated by the expression of pyruvate dehydrogenase kinase 3 (PDK3). In addition, the developmental competence of oocytes and the quality of blastocysts were also reduced after TBBPA treatment. These results demonstrated that TBBPA exposure impaired oocyte maturation and developmental competence by disrupting both nuclear and cytoplasmic maturation of the oocyte, which might have been caused by oxidative stress induced by mitochondrial dysfunction.

Ethnopharmacological Relevance: Atherosclerosis (AS) is one of major threatens of death worldwide, and vascular smooth muscle cell (VSMC) proliferation is an important characteristic in the progression of AS. Tribulus terrestris L. is a well-known Chinese Materia Medica for treating skin pruritus, vertigo and cardiovascular diseases in traditional Chinese medicine. However, its anti-AS activity and inhibition effect on VSMC proliferation are not fully elucidated., Aims: We hypothesize that the furostanol saponins enriched extract (FSEE) of T. terrestris L. presents anti-AS effect by inhibition of VSMC proliferation. The molecular action mechanism underlying the anti-VSMC proliferation effect of FSEE is also investigated., Materials and Methods: Apolipoprotein-E deficient (ApoE -/- ) mice and rat thoracic smooth muscle cell A7r5 were employed as the in vivo and in vitro models respectively to evaluate the anti- AS and VSMC proliferation effects of FSEE. In ApoE -/- mice, the amounts of total cholesterol, triglyceride, low density lipoprotein and high density lipoprotein in serum were measured by commercially available kits. The size of atherosclerotic plaque was observed by hematoxylin & eosin staining. The protein expressions of α-smooth muscle actin (α-SMA) and osteopontin (OPN) in the plaque were examined by immunohistochemistry. In A7r5 cells, the cell viability and proliferation were tested by MTT and Real Time Cell Analysis assays. The cell migration was evaluated by wound healing assay. Propidium iodide staining followed by flow cytometry was used to analyze the cell cycle progression. The expression of intracellular total and phosphorylated proteins including protein kinase B (Akt) and mitogen-activated protein kinases (MAPKs), such as mitogen-activated extracellular signal-regulated kinase (MEK), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), were detected by western blotting analysis., Results: FSEE significantly reduced the area of atherosclerotic plaque in high-fat diet-fed ApoE -/- mice. And FSEE increased the protein expression level of α-SMA and decreased the level of OPN in atherosclerotic plaque, which revealed the inhibition of VSMC phenotype switching and proliferation. In A7r5 cells, FSEE suppressed fetal bovine serum (FBS) or oxidized low density lipoprotein (oxLDL)-triggered VSMC proliferation and migration in a concentration dependent manner. FSEE protected against the elevation of cell numbers in S phase induced by FBS or oxLDL and the reduction of cell numbers in G 0 /G 1 phase induced by oxLDL. Moreover, the phosphorylation of Akt and MAPKs including MEK, ERK and JNK could be facilitated by FBS or oxLDL, while co-treatment of FSEE attenuated the phosphorylation of Akt induced by oxLDL as well as the phosphorylation of MEK and ERK induced by FBS. In addition, (25R)-terrestrinin B (JL-6), which was the main ingredient of FSEE, and its potential active pharmaceutical ingredients tigogenin (Tigo) and hecogenin (Heco) also significantly attenuated FBS or oxLDL-induced VSMC proliferation in A7r5 cells., Conclusion: FSEE presents potent anti- AS and VSMC proliferation activities and the underlying mechanism is likely to the suppression of Akt/MEK/ERK signaling. The active components of FSEE are JL-6 and its potential active pharmaceutical ingredients Tigo and Heco. So, FSEE and its active compounds may be potential therapeutic drug candidates for AS., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

piRNAs play pivotal roles in maintaining genome stability, regulating gene expression, and modulating development and immunity. However, there are few piRNA-associated studies on honey-bees, and the regulatory role of piRNAs in the development of bee guts is largely unknown. Here, the differential expression pattern of piRNAs during the developmental process of the European honey-bee ( Apis mellifera ) larval guts was analyzed, followed by investigation of the regulatory network and the potential function of differentially expressed piRNAs (DEpiRNAs) in regulating gut development. A total of 843 piRNAs were identified in the larval guts of A. mellifera ; among these, 764 piRNAs were shared by 4- (Am4 group), 5- (Am5 group), and 6-day-old (Am6 group) larval guts, while 11, 67, and one, respectively, were unique. The first base of piRNAs in each group had a cytosine (C) bias. Additionally, 61 up-regulated and 17 down-regulated piRNAs were identified in the "Am4 vs. Am5" comparison group, further targeting 9, 983 genes, which were involved in 50 GO terms and 142 pathways, while two up-regulated and five down-regulated piRNAs were detected in the "Am5 vs. Am6" comparison group, further targeting 1, 936 genes, which were engaged in 41 functional terms and 101 pathways. piR-ame-742536 and piR-ame-856650 in the "Am4 vs. Am5" comparison group as well as piR-ame-592661 and piR-ame-31653 in the "Am5 vs. Am6" comparison group were found to link to the highest number of targets. Further analysis indicated that targets of DEpiRNAs in these two comparison groups putatively regulate seven development-associated signaling pathways, seven immune-associated pathways, and three energy metabolism pathways. Moreover, the expression trends of five randomly selected DEpiRNAs were verified based on stem-loop RT-PCR and RT-qPCR. These results were suggestive of the overall alteration of piRNAs during the larval developmental process and demonstrated that DEpiRNAs potentially modulate development-, immune-, and energy metabolism-associated pathways by regulating the expression of corresponding genes via target binding, further affecting the development of A. mellifera larval guts. Our data offer a novel insight into the development of bee larval guts and lay a basis for clarifying the underlying mechanisms.

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.

In recent years, with the vigorous development and gradual deployment of new energy vehicles, more attention has been paid to the research on lithium-ion batteries (LIBs). Compared with the booming LIBs, lithium primary batteries (LPBs) own superiority in specific energy and self-discharge rate and are usually applied in special fields such as medical implantation, aerospace, and military. Widespread application in special fields also means more stringent requirements for LPBs in terms of energy density, working temperature range and shelf life. Therefore, how to obtain LPBs with high energy density, wide operational temperature range and long storage life is of great importance in future development. In view of the above, this paper reviews the latest research on LPBs in cathode, anode and electrolyte over the years, and puts forward relevant insights for LPBs, along with the intention to explore avenues for the design of LPBs components in the coming decades and promote further development in this field., (© 2022 The Chemical Society of Japan & Wiley-VCH GmbH.)

A novel copper-catalyzed cross-coupling of arylsulfonyl radicals with diazo compounds is described for the synthesis of various arylsulfones under mild conditions. In this reaction, the cheap, environmentally friendly, and readily available inorganic K 2 S 2 O 5 is employed as the sulfur dioxide source for providing arylsulfonyl radicals. In addition, a radical mechanism involving the insertion of sulfur dioxide with aryl radicals followed by the coupling of arylsulfonyl radicals with copper carbenes is proposed.

Background: Syphilis is a sexually transmitted infection that has been increasing in prevalence since the early 2000s. Ocular involvement occurs in a minority of patients and must be in the differential diagnosis for patients who present with red eye and uveitis., Case Report: A 29-year-old woman presented to the emergency department with a painful, mydriatic red eye. Review of systems revealed a rash as well as a recent genital lesion and, on further questioning, she admitted to a history of intravenous drug use and high-risk sexual activity. Ophthalmology was consulted and the patient was diagnosed with bilateral uveitis. Serologic testing was positive for syphilis, and she was admitted and treated with intravenous penicillin, with resolution of her uveitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Red eye is a common ocular symptom in patients presenting to the emergency department. The differential diagnosis of the red eye is broad and can range from benign etiologies, such as conjunctivitis, to life- and sight-threatening conditions, such as endogenous endophthalmitis. Systemic diseases such as syphilis may present with primarily ocular symptoms, and ocular syphilis must be identified and managed appropriately to prevent devastating sequelae., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The study aimed to investigate the effects of dietary distillers dried grains with solubles (DDGS) levels on growth performance, carcass characteristic, serum biochemical indexes, meat physical and chemical quality, nutrient utilization, and standardized ileal digestibility of amino acids (SIDAA) in Pekin ducks aged 11 to 42 d based on the evaluation of its SIDAA. A total of 560 eleven-day-old Cherry Valley ducks were randomly allotted to 5 treatments with 7 replicate pens per treatment and 16 ducks per pen based on the average body weight. Six isonitrogenous and isocaloric experimental diets were formulated on a digestible amino acid basis to produce diets containing 0, 5, 10, 15, and 20% DDGS, respectively. With increasing of dietary DDGS levels, a linear and quadratic reduction (P < 0.05) was observed in the body weight (BW) at d 42, average day gain (ADG) and average day feed intake (ADFI) from d 11 to 42, breast meat yield, the moisture and protein content in the breast meat, and dietary DM and EE utilization. Moreover, a linear and quadratic increase (P < 0.05) was observed in the b* value of the breast meat and serum total cholesterol and triglyceride concentrations. Compared with the control group, the group with 10% inclusion of DDGS exhibited no adverse effect on growth performance, carcass characteristics, serum biochemical indexes, meat physical and chemical quality, nutrient utilization, and the SIDAA of the diets (P > 0.05). These results suggested that 10% of corn DDGS can function as an alternative ingredient to corn and soybean meal, and the optimal levels of DDGS in the diets of ducks aged from 11 to 42 d depends more on its quality., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Phosphorescent iridium(III) complexes have been extensively investigated as cellular imaging reagents and sensors. The intracellular localization of the complexes is known to be closely related to their formal charge, molecular size, lipophilicity, and bioactive pendants. Herein, we reported four phosphorescent iridium(III) complexes with the diimine ligands being modified with ester or amide groups as imaging reagents for living cells. The complexes have the same positive charge and very similar molecular size and weight. The lipophilicity of the complexes is similar ranging from 1.45 to 2.14. Upon internalization into living HeLa cells, while complexes 2-4, like most other iridium(III) complexes, were localized in the cytoplasm, complex 1 unexpectedly stained the whole cells including nuclei. The nuclear uptake of complex 1 was not observed when the cells were pretreated with chlorpromazine or nocodazole, suggesting that clathrin and microtubules mediated the nuclear uptake of complex 1. Additionally, the nuclear uptake efficiency is related to the cell division cycle. The complex was mainly concentrated in the nucleus when the cells were in mitosis, and distributed in whole cells when the cells were in the interphases. Furthermore, complex 1 exhibited a longer luminescence lifetime in the nucleus than in the cytoplasm as revealed by photoluminescence lifetime imaging microscopy (PLIM). Incubation of the cells in the hypoxia environment elongated the lifetime of the cytoplasmic complex, but hardly affected the luminescence properties of the intranuclear complex.

Aim: Mutations in the SARS-CoV-2 spike (S) protein have dramatically changed the transmissibility and pathogenicity of the virus. Therefore, we studied the binding affinity of Omicron spike-receptor binding domain (S-RBD) with human ACE2 receptor. Materials & methods: We used pyDockWEB and HADDOCK 2.4 docking for our study. Results: Computational docking indicated higher binding affinity of Omicron S-RBD as compared with wild-type SARS-CoV-2 and Delta S-RBD with ACE2. Interface analysis suggested four mutated residues of Omicron S-RBD for its enhanced binding. We also showed decreased binding affinity of Omicron and Delta S-RBDs with monoclonal antibodies. Conclusion: Compared with wild-type SARS-CoV-2, Omicron S-RBD exhibit higher binding with ACE2 and lower affinity against monoclonal antibodies., (© 2022 Mirza S Baig.)

Rationale and Objectives: To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer., Materials and Methods: A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances., Results: In primary lesions study, model 1 was constructed by combining f value, original&#95;shape&#95;Sphericity and original&#95;firstorder&#95;Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original&#95;glszm&#95;Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively., Conclusion: Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The study aimed to determine the ileal phosphorus (P) digestibility (iPD) and the excreta P retention (ePR) of 5 monodicalcium phosphate (MCP) samples and 3 dicalcium phosphate (DCP) samples in broiler chickens and in Pekin ducks using the substitution method. A total of 720, 21-d-old Arbor Acres broiler chickens in experiment 1 and 720, 15-d-old Pekin ducks in experiment 2 were randomly allocated to 9 dietary treatments with 8 replicate cages (10 birds/cage) based on the similar mean body weight, respectively. The collection of excreta (for 72 h after a 3-d acclimation) and ileal digesta (after 6 d of feeding experimental diets) was done. The results showed the average iPD/ePR of MCP and DCP for broilers were 83.11%/74.52% and 75.34%/69.46% and for ducks were 79.37%/80.02% and 75.74%/76.44%, respectively. The iPD/ePR of MCP in broilers and the ePR of MCP in ducks were markedly higher (P < 0.05) than those of DCP. Our data suggest that using the substitution method to evaluate the bioavailability of feed phosphates has its own advantages; MCP has higher biological availability than DCP for broilers and ducks., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to explore the toxic effects of different heavy metals in combination with their deposition and ion homeostasis in the reproductive organs and eggs of laying hens, as well as the alleviating action of selenized yeast. A total of 160 Lohmann pink-shell laying hens (63-week-old) were randomly allocated into four treatments with 10 replicates of four hens each. The four dietary treatments were the corn-soybean meal basal dietary (control; CON ); the CON dietary supplemented with 0.4 mg/kg selenium from selenized yeast ( Se ); the CON dietary supplemented with 5 mg/kg Cd + 50 mg/kg Pb +3 mg/kg Hg + 5 mg/kg Cr ( HEM ), and the HEM dietary supplemented with 0.4 mg/kg selenium from selenized yeast ( HEM+Se ). The dietary HEM significantly increased Cd, Pb, and Hg deposition in the egg yolk and ovary, and Cd and Hg deposition in the oviduct and in the follicular wall ( p < 0.05). The HEM elevated Fe concentration in the egg yolk, ovary, and oviduct ( p < 0.05). The HEM decreased Mn concentration in the egg yolk, Fe, Mn, and Zn concentrations in the egg white, Cu concentration in the ovary, Mg concentration in the oviduct, as well as Ca, Cu, Zn, and Mg concentrations in the follicular walls ( p < 0.05). Dietary Se addition elevated Se concentration in the egg yolk, oviduct, and follicular walls and Mg concentration ( p < 0.05) in the oviduct, whereas it reduced Fe concentration in the oviduct compared with the HEM-treated hens. Some positive or negative correlations among these elements were observed. Canonical Correlation Analysis showed that the concentrations of Pb and Hg in the egg yolk were positively correlated with those in the ovary. The concentration of Cd in the egg white was positively correlated with that in the oviduct. In summary, dietary Cd, Pb, Hg, and Cr in combination caused ion loss and deposition of HEM in reproductive organs of laying hens. Dietary Se addition at 0.4 mg/kg from selenized yeast alleviated the negative effects of HEM on Fe and Mg ion disorder in the oviduct and follicle wall of hens., Competing Interests: BW is employed by Chelota biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Li, Jiang, Kim, Wu, Liu, Wang, Lin, Zhang, Song, Zhang, Wu, Liang and Bai.)

Purpose: A retrospective population-based study to investigate racial and socioeconomic disparities in patients diagnosed with ocular surface squamous neoplasia (OSSN)., Methods: To explore racial disparity, we selected OSSN patients with known age, insurance, gender and zip code-level income and education from the National Cancer Database (NCDB). Comparisons of clinical and socioeconomic variables stratified by race were made with the chi-square or Mann-Whitney tests. Survival outcome was examined a Cox regression model., Results: Of the 2,402 identified patients from 2004 to 2015, 117 were black. Unadjusted differences were found between groups in regard to age, histology, insurance, income, and education. Black patients in comparison to white patients were younger (mean age: 62 years vs. 70 years; p < .001), represented a higher proportion of Medicaid use (10.3% vs. 3.2%; p < .001) or uninsured (10.3% vs. 2.7%; p < .001), and were more likely to reside in areas of low educational attainment (32.5% vs. 16.1% of whites; p < .001). Multivariate analysis found significantly higher risk of death in patients who were male (HR: 1.66, 95% CI 1.37-2.01) or black (HR: 1.57, 95% CI 1.03-2.38)., Conclusion: Disparities in socioeconomic factors were observed in black patients with OSSN. OSSN occurred earlier in blacks, who were also socioeconomically disadvantaged and faced higher risk of death.

In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A 2 -T 2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p < 0.01) in function distribution between the two clusters . Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A 2 versus T 2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence., (© 2021. The Author(s).)

Purpose: The aim of the present study was to evaluate the effects of dexmedetomidine compared with propofol in mechanically ventilated patients with sepsis. Methods: We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials comparing the effects of dexmedetomidine versus propofol in septic patients requiring mechanical ventilation from inception to December 2021. The primary outcome was 28/30-day mortality and secondary outcomes were ventilator-free days and the length of ICU stay. Pooled relative risk (RR), mean deviation (MD), along with 95% confidence intervals (CI) were used to express outcomes by the software of Review Manager 5.3. Results: Seven studies with a total of 1,212 patients were eligible for meta-analysis. The results primarily showed that dexmedetomidine had no significant effects on the 28/30-day mortality (RR = 1.04 [0.85-1.26], p = 0.70, I 2 = 3%). As for secondary outcomes, the administration of dexmedetomidine was not associated with longer-ventilator-free days (MD = 0.50 [-2.15, 3.15], p = 0.71, I 2 = 24%) compared with propofol. However, our results revealed dexmedetomidine could shorten the length of ICU stay (MD = -0.76 [-1.34, -0.18], p = 0.01, I 2 = 33%). Conclusion: Administration of dexmedetomidine for sedation in septic patients who required mechanical ventilation had no effect on 28/30-day mortality and ventilator-free days, but it could shorten the length of ICU stay., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Dong, Zhang and Bai.)

The study aimed to investigate the effects of dietary corn germ meal (CGM) levels on growth performance, carcass characteristic, serum biochemical indexes, meat physical and chemical quality, and standardized ileal digestibility of amino acids (SIDAA) in Pekin ducks from 10 to 42 d of age. A total of 420 ten-day-old Cherry Valley ducks were randomly allotted to 5 treatments with 6 replicate cages per treatment and 14 ducks per cages based on mean body weight. Five isonitrogenous and isocaloric experimental diets were formulated on a digestible amino acid basis to produce diets containing 0, 3, 6, 9, or 12% CGM. Results showed: 1) Compared with other groups, ducks fed 12% CGM significantly increased (P < 0.05) the feed to gain ratio. 2) Dietary CGM levels had no effect (P > 0.05) on the carcass traits and breast meat physical quality; but the content of crude protein presented a linear decrease (P < 0.05) in breast meat with increasing dietary CGM levels. 3) Serum biochemical indices (e.g., alanine aminotransferase, aspartate aminotransferase, glucose, high density lipoprotein cholesterol, total cholesterol, triglyceride, total protein, and urea) showed no significant differences among all groups (P > 0.05). 4) The levels of CGM had no significant effect on SIDAA of diets (P > 0.05), except for cysteine which showed a quadratic increase (P < 0.05). These results suggested that the optimal levels of CGM in diets for meat duck aged from 10 to 42 d should be below 9% based on feed to gain ratio and the content of crude protein in breast meat., (Copyright © 2022. Published by Elsevier Inc.)

Retinal ganglion cell (RGC) transplantation has the potential to restore vision in optic neuropathy, but donor neuron survival and retinal integration remain challenging. Here, we present a protocol for ex vivo human RGC transplantation on flatmounted murine organotypic retinal explants, providing a robust platform for studying donor RGC survival, dendritic stratification, topographic distribution, donor-host interactions, and pro-engraftment strategies. The protocol includes microscopy-based analyses to evaluate donor cell engraftment and can be adapted to various donor cell types or culture systems. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021a, 2021b)., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Fluorescent/phosphorescent dual-emissive polymers or hybrids consisting of both fluorophore and phosphor have been used as self-calibrating probes and imaging reagents for cellular molecular oxygen. Oxygen selectively quenches the phosphorescence and the fluorescence serves as an internal reference. The phosphorescence/fluorescence ratio is used as a quantitative indicator of oxygen content. In wavelength-ratiometric probes, the fluorophore and phosphor are designed to emit at different wavelengths. It is easy to achieve spectral separation, but the phosphorescence/fluorescence ratio fluctuates due to the difference in the absorption and scattering of light at different wavelengths by biological samples. Herein we reported a lifetime-ratiometric luminescent polymeric probe where the fluorophore and phosphor emitted at the same wavelength. Spectral separation was achieved based on the difference in their excited-state lifetimes via time-resolved luminescence analysis and imaging. The probe exhibited a phosphorescence lifetime of about 931 ns with a phosphorescence/fluorescence ratio of 4.49 in deaerated aqueous buffer. The lifetime was shortened to 251 ns and the ratio decreased to 1.08 in oxygen saturated solution because of phosphorescence quenching. The utilization of the probe for quantitative oxygen sensing and mapping in living HeLa cells was demonstrated using calibration curves obtained from fixed cells.

Ammonia oxidation is an important process in both the natural nitrogen cycle and nitrogen removal from engineered ecosystems. Recently, a new ammonia oxidation pathway termed Dirammox ( dir ect amm onia ox idation, NH 3 →NH 2 OH→N 2 ) has been identified in Alcaligenes ammonioxydans . However, whether Dirammox is present in other microbes, as well as its genetic regulation, remains unknown. In this study, it was found that the metabolically versatile bacterium Alcaligenes faecalis strain JQ135 could efficiently convert ammonia into N 2 via NH 2 OH under aerobic conditions. Genetic deletion and complementation results suggest that dnfABC is responsible for the ammonia oxidation to N 2 in this strain. Strain JQ135 also employs aerobic denitrification, mainly producing N 2 O and trace amounts of N 2 , with nitrite as the sole nitrogen source. Deletion of the nirK and nosZ genes, which are essential for denitrification, did not impair the capability of JQ135 to oxidize ammonia to N 2 (i.e., Dirammox is independent of denitrification). Furthermore, it was also demonstrated that pod (which encodes pyruvic oxime dioxygenase) was not involved in Dirammox and that AFA&#95;16745 (which was previously annotated as ammonia monooxygenase and is widespread in heterotrophic bacteria) was not an ammonia monooxygenase. The MocR-family transcriptional regulator DnfR was characterized as an activator of the dnfABC operon with the binding motif 5'-TGGTCTGT-3' in the promoter region. A bioinformatic survey showed that homologs of dnf genes are widely distributed in heterotrophic bacteria. In conclusion, this work demonstrates that, besides A. ammonioxydans, Dirammox occurs in other bacteria and is regulated by the MocR-family transcriptional regulator DnfR. IMPORTANCE Microbial ammonia oxidation is a key and rate-limiting step of the nitrogen cycle. Three previously known ammonia oxidation pathways (i.e., nitrification, anaerobic ammonia oxidation [Anammox], and complete ammonia oxidation [Comammox]) are mediated by autotrophic microbes. However, the genetic foundations of ammonia oxidation by heterotrophic microorganisms have not been investigated in depth. Recently, a previously unknown pathway, termed direct ammonia oxidation to N 2 (Dirammox), has been identified in the heterotrophic bacterium Alcaligenes ammonioxydans HO-1. This paper shows that, in the metabolically versatile bacterium Alcaligenes faecalis JQ135, the Dirammox pathway is mediated by dnf genes, which are independent of the denitrification pathway. A bioinformatic survey suggests that homologs of dnf genes are widely distributed in bacteria. These findings enhance the understanding of the molecular mechanisms of heterotrophic ammonia oxidation to N 2 .

Competing Interests: The authors report no conflicts of interest.

The spines of cucumber fruit not only have important commercial value but are also a classical tissue to study cell division and differentiation modes of multicellular trichomes. It has been reported that CsTs (C-type Lectin receptor-like kinase) can influence the development of fruit spines. In this study, we took a pair of cucumber materials defined as hard (Ts, wild type) and tender spines ( ts , mutant) and defined the developmental process of fruit spines as consisting of four stages (stage I to stage IV) by continuously observing by microscope and SEM. Comparisons of transcriptome profiles at different development stages of wild-type spines showed that 803 and 722 genes were upregulated in the stalk (stage II and stage III) and base (stage IV) development stages of fruit spines, respectively. The function analysis of DEGs showed that genes related to auxin polar transport and HD-ZIP transcription factor are significantly upregulated during the development of the stalk. bHLH transcription factors and cytoskeleton-related genes were significantly upregulated during the development of the base. In addition, stage III is the key point for the difference between wild-type and mutant spines. We detected 628 DEGs between wild type and mutant at stage III. These DEGs are mainly involved in the calcium signaling of the cytoskeleton and auxin polar transport. Coincidentally, we found that CsVTI11, a factor involved in auxin signal transmission, can interact with CsTs in vivo , but this interaction does not occur between CsVTI11 and Csts, further suggesting that CsTs may regulate the development of fruit spines by influencing cell polarity. These results provide useful tools to study the molecular networks associated with cucumber fruit spine development and elucidate the biological pathways that C-type Lectin receptor-like kinase plays in regulating the development of fruit spines., Competing Interests: J-AP was employed by Tianjin Derit Seeds Company Limited, Tianjin, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Wang, Zhang, Yu, Qin, Pang, Sun, Zhang, He, Cai and Pan.)

A novel and mild metal-free catalyzed radical-mediated cascade spirocyclization of N -benzylacrylamides with polyhaloalkanes is proposed for the preparation of polyhalo-substituted azaspirocyclohexadienones. Notably, polyhaloalkanes are employed as efficient alkyl radical sources via the cleavage of C(sp 3 )-H bonds. This protocol undergoes a cascade radical addition and intramolecular cyclization/dearomatization process, and enables the easy construction of multiple chemical bonds and a spiro ring in a single reaction.

This study was conducted to investigate the effect of different varieties of rapeseed meal (RSM) with different concentrations of glucosinolates (Gls) and erucic acid (EA) on performance and egg quality of laying ducks. A total of 576 twenty eight-wk-old laying ducks were randomly allocated to 4 treatments. Each treatment had 8 replicates of 18 laying ducks raised in 6 adjacent cages with 3 laying ducks per cage. The control diet was corn soybean meal based without RSM. Three varieties of RSM varying in Gls concentrations were supplemented to the base diet at 10% by substituting soybean meal to formulate the three RSM diets. The experiment lasted 12 wk. Diets with 10% RSM decreased average egg weight (P < 0.01) and feed intake (P = 0.07) compared with the control diet, but there was no significant difference in laying performance among the 3 RSM diets. RSM increased color value (P < 0.05) and crude protein (CP) content (P < 0.05) of yolk compared with the control diet, but had no significant effects on the other egg quality indexes including eggshell strength, albumen height, Haugh unit, and the composition ratio of eggshell, albumen and yolk. RSM decreased total monounsaturated fatty acids (MUFA) (P < 0.01) and increased total polyunsaturated fatty acids (PUFA) (P < 0.01) of yolk, but total saturated fatty acids (SFA) proportions and UFA/SFA ratio of egg yolk were not significantly affected by RSM. RSM increased deposition of trimethylamine (TMA) and 5-vinyl-1,3-oxazolidine-2-thione (5-VOT) in yolk (P < 0.01); moreover, the high Gls RSM increased deposition of TMA (P < 0.01) and 5-VOT in yolk (P < 0.01) compared with the RSM varieties low in Gls. These results suggested that dietary inclusion of 10% RSM decreased egg weight of laying ducks, and affected yolk quality especially yolk color, fatty acid profile, CP, TMA, and 5-VOT content of yolk. Moreover, RSM with higher Gls concentration resulted in higher deposition of TMA and 5-VOT in egg yolk., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Colorectal cancer ranks among the most common cancers. 5-Fluorouracil (5-FU) based first-line chemotherapy for colorectal cancer treatment often leads to chemoresistance and gastrointestinal mucositis., Purpose: This study aimed to find potential therapeutic agents from herbal medicine with anti-colorectal cancer and anti-mucositis activities., Methods: Chinese medicine theory, network pharmacology analyses, and antioxidant activity coupled with liquid chromatography tandem mass spectrometry analyses were used to identify potential bioactive compounds. HT-29 human colorectal cancer cell culture and xenograft tumor models were employed to study anti-colorectal cancer efficacy. Lipopolysaccharide-induced RAW 264.7 and 5-FU treated Dark Agouti rats were used to evaluate anti-inflammatory and anti-mucositis activities. Histological staining, immunofluorescence imaging, western blots, and flow cytometric analyses were employed to explore the underlying mechanisms., Results: Both Chinese medicine theory and network pharmacology analyses indicated pomegranate peels as a potential anti-colorectal cancer and anti-mucositis agent. Antioxidant activity coupled with liquid chromatography tandem mass spectrometry analyses revealed granatin B and punicalagin as the most potent antioxidant compounds in pomegranate peels. Granatin B and punicalagin demonstrated superior anti-colorectal cancer activities in both cell culture and xenograft tumor models. Granatin B and punicalagin also exhibited strong anti-inflammatory activities in lipopolysaccharide-induced RAW264.7 cells and anti-mucositis activities in 5-FU-treated rats. Mechanistic studies revealed that granatin B and punicalagin induced reactive oxygen species-mediated S-phase cell cycle arrest and apoptosis in HT-29 cells. Moreover, these compounds sensitized HT-29 cells to 5-FU-induced cell death and S-phase cell cycle arrest., Conclusion: We report that granatin B and punicalagin exhibit superior anti-colorectal cancer and anti-mucositis activities. To the best of our knowledge, these results are novel and suggest that utilizing phenols from herbal medicine, such as granatin B and punicalagin, to target reactive oxygen species may be an innovative therapy to treat colorectal cancer and intestinal mucositis., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Electrically controlling photoluminescence has attracted great research interest and offers many opportunities for technological developments. Electroluminochromic materials undergo redox reactions under low-voltage stimuli to achieve reversible luminescence switching. Till now, photoluminescence switching of a single molecule caused by electrical stimuli is restricted to intensity response because the redox-active moieties are good electron donors or acceptors and electrical stimuli can regulate the photoinduced electron-transfer and affect the luminescence intensity. In this work, the manipulation of the electroluminochromism behavior of a series of viologen-substituted iridium(III) complexes through the regulation of ligand orbital energy levels and electronic communication between the viologen pendants and the iridium(III) complex core is reported. Electrochemical redox reactions reversibly modulate either the luminescence quenching effect or the push-pull electronic effect of the viologen substituents, achieving multicolor "on-off" luminescence response toward electrical stimuli and luminescence manipulation between two emissive states with different wavelengths and lifetimes. To illustrate the promising applications of these electroluminochromic materials, recording and displaying luminescence information under electrical stimuli are demonstrated. Information encryption is realized by letting the electroluminochromism occur in the near-infrared region or in the time domain. Near-infrared camera or time-resolved luminescence analysis can be used to help read the invisible information., (© 2021 Wiley-VCH GmbH.)

Aim: To explore the efficacy of the orthokeratology lens for anisometropic myopia progression., Methods: A retrospective study was performed. Cycloplegic refraction and axial length (AL) were collected from 50 children (10.52±1.72y) who visited Peking University Third Hospital from July 2015 to August 2020. These children's one eyes (Group A) received monocular orthokeratology lenses at first, after different durations (12.20±6.94mo), their contralateral eyes (Group B) developed myopia and receive orthokeratology as well. The data in 1-year of binocular period were recorded. AL growth rate (difference of follow-up and baseline per month) were compared between two groups by paired t test. Interocular differences of AL were compared by Wilcoxon test., Results: During monocular period, the AL growth rate of the Group A (0.008±0.022 mm/mo) was significantly slower than that of the Group B (0.038±0.018 mm/mo; P <0.0001). However, during binocular period, the AL growth rate of the Group A (0.026±0.014 mm/mo) was significantly faster than that of the Group B (0.016±0.015 mm/mo; P <0.0001). The AL difference between both eyes was 0.6 (0.46) mm, then significantly decreased to 0.22 (0.39) mm when started binocular treatment ( P <0.0001). However, it was significantly increased to 0.30 (0.32) mm after a year ( P <0.0001), but still significantly lower than baseline ( P <0.0001)., Conclusion: The orthokeratology lens is efficient for control the AL elongation of monocular myopia eyes and reduce anisometropia. For the condition that the contralateral eyes develop myopia and receive orthokeratology lens later, there is no efficiency observed on control interocular difference of AL during binocular treatment., (International Journal of Ophthalmology Press.)

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease and skin microbiota dysbiosis shows an important role in the pathogenesis of AD. Effects of treatment on skin microbiota for patients with AD have been evaluated in recent years; however, the results remained controversial across studies. This systematic review will summarise studies evaluating the effect of treatments on skin microbiota among patients with AD., Methods and Analysis: We will search PubMed, EMBASE, Web of Science, ClinicalTrials.gov and Chinese Clinical Trial Registry in November 2021; other data sources will also be considered, including searching specific authors and screening references cited in the enrolled articles. Interventional studies, which enrolled patients with AD receiving treatments and reported treatment-related skin microbiota changes, will be included. Our primary outcomes include skin microbiota diversity and treatment-related differential microbes; the secondary outcomes include microbiota functions and microbial interactions. Risk of bias assessment will be performed using Cochrane risk-of-bias tool for randomised trials, risk of bias in non-randomised studies of interventions and methodological index for non-randomised studies. Two researchers will independently perform study selection, data extraction and risk of bias assessment, with disagreements resolved by group discussions. Subgroup analyses will be performed according to different types of treatment for AD., Ethics and Dissemination: Ethics approval is not required for this systematic review. Findings will be disseminated via peer-reviewed publication or conference proceedings., Prospero Registration Number: CRD42021246566., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Differences in traits between lianas and trees in tropical forests have been studied extensively; however, few have compared the ecological strategies of lianas from different habitats. Here, we measured 25 leaf and stem traits concerning leaf anatomy, morphology, physiology and stem hydraulics for 17 liana species from a tropical seasonal rainforest and for 19 liana species from a valley savanna in south-west China. We found that savanna lianas had higher vessel density, wood density and lower hydraulically weighted vessel diameter and theoretical hydraulic conductivity than tropical seasonal rainforest lianas. Compared with tropical seasonal rainforest lianas, savanna lianas also showed higher leaf dry matter content, carbon isotope composition (δ13C), photosynthetic water use efficiency, ratio of nitrogen to phosphorus, photosynthetic phosphorus use efficiency and lower leaf size, stomatal conductance and nitrogen, phosphorus and potassium concentrations. Interestingly, no differences in light-saturated photosynthetic rate were found between savanna and tropical seasonal rainforest lianas either on mass or area basis. This is probably due to the higher water and nutrient use efficiencies of savanna lianas. A principal component analysis revealed that savanna and tropical seasonal rainforest lianas were significantly separated along the first axis, which was strongly associated with acquisitive or conservative resource use strategy. Leaf and stem functional traits were coordinated across lianas, but the coordination or trade-off was stronger in the savanna than in the tropical seasonal rainforest. In conclusion, a relatively conservative (slow) strategy concerning water and nutrient use may benefit the savanna lianas, while higher nutrient and water use efficiencies allow them to maintain similar photosynthesis as tropical seasonal rainforest species. Our results clearly showed divergences in functional traits between lianas from savanna and tropical seasonal rainforest, suggesting that enhanced water and nutrient use efficiencies might contribute to the distribution of lianas in savanna ecosystems., (© The Author(s) 2021. Published by Oxford University Press.)

Aim: Splicing factor proline and glutamine rich (SFPQ) is an RNA-DNA binding protein that is dysregulated in Alzheimer's disease and frontotemporal dementia. Dysregulation of SFPQ, specifically increased intron retention and nuclear depletion, has been linked to several genetic subtypes of amyotrophic lateral sclerosis (ALS), suggesting that SFPQ pathology may be a common feature of this heterogeneous disease. Our study aimed to investigate this hypothesis by providing the first comprehensive assessment of SFPQ pathology in large ALS case-control cohorts., Methods: We examined SFPQ at the RNA, protein and DNA levels. SFPQ RNA expression and intron retention were examined using RNA-sequencing and quantitative PCR. SFPQ protein expression was assessed by immunoblotting and immunofluorescent staining. At the DNA level, SFPQ was examined for genetic variation novel to ALS patients., Results: At the RNA level, retention of SFPQ intron nine was significantly increased in ALS patients' motor cortex. In addition, SFPQ RNA expression was significantly reduced in the central nervous system, but not blood, of patients. At the protein level, neither nuclear depletion nor reduced expression of SFPQ was found to be a consistent feature of spinal motor neurons. However, SFPQ-positive ubiquitinated protein aggregates were observed in patients' spinal motor neurons. At the DNA level, our genetic screen identified two novel and two rare SFPQ sequence variants not previously reported in the literature., Conclusions: Our findings confirm dysregulation of SFPQ as a pathological feature of the central nervous system of ALS patients and indicate that investigation of the functional consequences of this pathology will provide insight into ALS biology., (© 2021 British Neuropathological Society.)

It has been shown that enzyme-treated plant protein can increase performance and promote intestinal health, and save dietary protein. However, our understanding of the effects of enzyme-treated soy protein on performance and intestine function in laying hens, and its rational use, remains limited. The experiment was conducted to study the effect of enzyme-treated soy protein (ETSP) in different nutrient density diets on performance, egg quality, digestive enzyme activity and mRNA expression of amino acid transporters of laying hens. A total of 1 200 Lohmann laying hens (52 wk of age) was randomly divided into a 3 × 2 factorial design that included three nutrient levels: [positive control (PC), metabolisable energy (ME): 2 680 kcal/kg, CP: 15.5%; negative control 1 (NC1), ME: 2 630 kcal/kg, CP: 15%; negative control 2 (NC2), ME:2 580 kcal/kg, CP: 14.5%] and 2 ETSP levels (0 and 0.5%) for 12 weeks. Each treatment had 10 replicates with 20 birds. With the decrease of dietary nutrition density, egg production rate (P = 0.07) and feed conversion ratio (FCR) (P = 0.06) were reduced. Yolk colour was decreased, and yolk index was increased. Supplemented ETSP improved FCR (P = 0.05) and qualified egg rate (P < 0.05). The mass loss rate of egg was decreased after storage for 30 days (P < 0.05). An interaction between nutrient density and ETSP was observed on albumen height and Haugh unit (P < 0.05), and the effects were most noticeable in hens fed 0.5% ETSP in NC2 group. An increase in the activity of trypsin in duodenum (P < 0.05) and the relative expressions of jejunum peptide transporter 1 (PepT1) (P < 0.05) and B 0 system neutral amino acid transport carrier (B 0 AT) mRNA (P < 0.01) was observed during ETSP supplementation. The nutrient density and ETSP supplementation had no significant effect on microbiota in the cecal contents. Overall, the results in this study indicated that the ME decreased 100 kcal/kg and CP decreased 1% in diet of laying hens had a decreasing trend on production performance, no effects on enzyme activity, amino acid transporter mRNA, and gut microbiota, whereas 0.5% ETSP can increase activity of trypsin, PepT1 and B 0 AT mRNA relative expressions, and improve FCR, qualified egg rate., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological-genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Teleradiology has become one of the most important approaches to virtual clinical diagnosis; its importance has only grown during the coronavirus 2019 pandemic. In developing countries, asking patients to take photographs of their images using a smartphone can facilitate the process and help keep its costs down. However, the images taken by patients with smartphones often are of poor quality, and there is no regulation or standard instruction about how to use smartphones to take photographs of medical examination images effectively. These problems limit the use of smartphones in remote diagnosis and treatment., Questions/purposes: To formulate a set of guidelines for the most appropriate and effective use of smartphones to capture images (radiographs, CT images, and MR images), and to determine whether these guidelines are more effectively adopted by patients of differing ages and genders., Methods: In this prospective study, a set of step-by-step instructions was created with the goal of helping patients take better smartphone photographs of orthopaedic diagnostic images for transfer to telemedicine services. Following the advice of surgeons, experts in smartphone technology, imaging experts, and suggestions from patients, the instructions were modified based on clinical experience and finalized with the goals of simplicity, clarity, and convenience. Potentially eligible patients were older than 18 years, had no cognitive impairment, and used smart phones. Based on that, 256 participants (patients or their relatives and friends) who visited the orthopaedic department of our hospital from June to October 2020 potentially qualified for this study. A total of 11% (29) declined to participate, leaving 89% (227) for analysis here. Their mean age was 36 ± 11 years, 50% were women (113 of 227), and the patient himself/herself represented in 34% (78 of 227) of participants while relatives or friends of patients made up 66% (149 of 227) of the group. In this study, the diagnoses included spinal stenosis (47% [107 of 227]), disc herniation without spinal stenosis (31% [71 of 227]), vertebral fractures (14% [32 of 227]), and other (7% [17 of 227]). Each study participant first took photographs of their original medical images based on their own knowledge of how to use the smartphone camera function; each participant then took pictures of their original images again after receiving our instructional guidance. Three senior spine surgeons (YZ, TQL, TCM) in our hospital analyzed, in a blinded manner, the instructed and uninstructed imaging files based on image clarity (the content of the image is complete, the text information in the image is clearly visible, there is neither reflection nor shadow in the image) and image position (it is not tilted, curled, inverted, or reversed). If either of these conditions was not satisfied, the picture quality was deemed unacceptable; two of three judges' votes determined the outcome. Interobserver reliability with kappa values for the three judges were 0.89 (YZ versus TQL), 0.92 (YZ versus TCM), and 0.90 (TQL versus TCM)., Results: In this study, the overall proportion of smartphone medical images deemed satisfactory increased from 40% (91 of 227) for uninstructed participants to 86% (196 of 227) for instructed participants (risk ratio 2.15 [95% CI 1.82 to 2.55]; p<0.001). The proportion of acceptable-quality images in different age groups improved after instruction, except for in patients aged 51 years or older (3 of 17 uninstructed participants versus 8 of 17 instructed participants; RR 2.67 [95% CI 0.85 to 8.37]; p = 0.07). The proportion of acceptable-quality images in both genders improved after instruction, but there was no difference between the genders., Conclusion: We believe our guidelines for patients who wish to take smartphone photographs of their medical images will decrease image transmission cost and facilitate orthopaedic telemedicine consultations. However, it appears that patients older than 50 years are more likely to have difficulty with this approach, and if so, they may benefit from more hands-on assistance from clinic staff or younger relatives or friends. The degree to which our findings are culture-specific should be verified by other studies in other settings, but on the face of it, there is little reason to believe our findings would not generalize to a reasonable degree. Other studies in more heterogeneous populations should also evaluate factors related to levels of educational attainment and wealth differences, but in the meantime, our findings can give clinical teams an idea of which patients may need a little extra assistance., Level of Evidence: Level II, therapeutic study., Competing Interests: Each author certifies that neither he or she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2021 by the Association of Bone and Joint Surgeons.)

Objective: To investigate the changes of occlusal delay time, percentage of occlusal force and patients' subjective satisfaction of masticatory function for single implant crown in one year after the application of space reserved occlusion design. To provide data support and suggestions for clinical occlusion design. Methods: Patients who had received single posterior dental implant restoration in Department of Prosthodontics, Capital Medical University School of Stomatology from January 2019 to December 2019 were selected. At 0.5, 3, 6 and 12 months after restoration, the T-scan Ⅲ occlusal analyzer was used to detect and record the initial occlusal contact time of the natural tooth and implanted single crown, the occlusal force percentage of single implant prosthesis and corresponding tooth on the contralateral side (control teeth) on the contralateral side (control teeth) were also recorded. Subjective satisfaction with the masticatory function of the implants was recorded using visual analogue scale (VAS). The changes of occlusal delay time (the difference of the initial occlusal time between implant restoration and the natural teeth), percentage of occlusal force and patients' subjective feeling with time were analyzed. All data were analyzed by repeated measurement analysis of variance, bilatteral P <0.01 was considered statistically significant. Results: A total of 48 patients aged (36.8±8.4) years (23 males, 25 females, aged 23-50 years) were recruited. The occlusal delay time at 0.5 months was 0.15 (0.08, 0.20) s, at 3 months was 0.11 (0.06, 0.16) s, at 6 months was 0.07 (0.03, 0.13) s and at 12 months was 0.06 (0.03, 0.10) s. The occlusal delay time was shortened at every two time points, and the occlusal force percentage of the implant crown increased significantly. The percentage of occlusal force of implant prosthesis at 0.5 months was (7.7±4.8)%, at 3 months was (10.6±5.9)%, at 6 months was (12.3±6.2)% and at 12 months was (13.2±6.7)%. The most significant change was during the period of 0.5-3 months. At 0.5 months, the occlusal force of implant prosthesis was significantly lower than that of control teeth (14.3±6.5)% ( P <0.01). The VAS score at 0.5 months was (7.06±1.64) and was (8.71±0.74) at 12 months. The score was increased and the difference was statistically significant from 3 month to 12 month ( P <0.01). Conclusions: The change of occlusal force percentage of single posterior dental implant is most obvious within 3 months after restoration. The occlusal condition should be reexamined and adjust occlusal after 3 months of implant restoration as appropriate.

Objective: Currently, coronavirus disease 2019 (COVID-19) has spread worldwide and become a global health concern. Here, we report a familial cluster of six patients infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) in a northern Chinese region and share our local experience with regard the control of COVID-19., Methods: The demographic data, clinical features, laboratory examinations, and epidemiological characteristics of enrolled cases were collected and analyzed. Two family members (Cases 1 and 2) had Hubei exposure history and were admitted to the hospital with a confirmed diagnosis of COVID-19; eight familial members who had contact with them during the incubation period underwent quarantine in a hospital. We closely followed up all the family members and analyzed their clinical outcome., Results: Case 3 had negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) results but was suspected to have COVID-19 because of radiographic abnormalities. Cases 4 and 5 developed symptomatic COVID-19. Case 6 was considered an asymptomatic carrier as his SARS-CoV-2 RT-PCR result was positive. The other four family members with close contacts to COVID-19 patients had no evidence of SARS-CoV-2 infection., Conclusions: Our findings suggest that COVID-19 has infectivity during the incubation period and preventive quarantine is effective for controlling an outbreak of COVID-19 infection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.

Background: Sperm acquire the ability to fertilize ova through a complex process of epididymal maturation. To identify the functions of genes expressed in the proximal epididymis, mouse models specific to this region are needed., Methods and Results: A Lcn8-Cre knock-in mouse line was generated using CRISPR/Cas9 technology. A 37 bp coding sequence of Lcn8 from the ATG start codon was replaced by an NLS-Cre-polyA cassette, resulting in Cre expression and the absence of Lcn8. Epididymal initial segment-specific Cre expression was identified using RT-PCR and western blotting, and the spatial-temporal Cre activity was further confirmed by using the Rosa26 tdTomato reporter mice. Immunofluorescence staining showed that active Cre recombinase was present in the principal cells. Histological analyses of sperm and epididymides, and the four-month mating tests, were used to confirm that Cre expression did not affect normal development and male fecundity., Conclusions: The novel Lcn8-Cre mice can be used to establish epididymal initial segment-specific conditional knock-out mouse models., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Spermatozoa released from testes undergo a maturation process and acquire the capacity to fertilize ova through epididymal transit. The epididymis is divided into four regions, each with unique morphology, gene profile, luminal microenvironment and distinct function. To study the functions of relevant genes in the epididymal initial segment (IS), a novel IS-specific mouse model, Lcn9-Cre knock-in (KI) mouse line was generated via CRISPR/Cas9 technology. The TAG stop codon was replaced by a 2A-NLS-Cre cassette, resulting in the co-expression of Lcn9 and Cre recombinase. IS-specific Cre expression was first observed from postnatal day 17. Using the Rosa26tdTomato reporter mice, the Cre-mediated DNA recombination was detected exclusively in principal cells. The epididymal IS-specific Cre activity in vivo was further confirmed using Lcn9-Cre mice crossed with a mouse strain carrying Tsc1 floxed alleles (Tsc1flox/+). Cre expression did not affect either normal development or male fecundity. Different from any epididymis-specific Cre mice reported previously, the novel Lcn9-Cre mouse line can be used to introduce entire IS-specific conditional gene editing for gene functional study., Competing Interests: The authors have declared that no competing interests exist.

Simultaneous analysis of luminescence signals of multiple probes can improve the accuracy and efficiency of biosensing and bioimaging. Analysis of multiple signals at different wavelengths usually suffers from spectral overlap, possible energy transfer, and difference in detection efficiency. Herein, we reported a polymeric luminescent probe, which was composed of a phenothiazine-based fluorescent compound and a phosphorescent iridium(iii) complex. Both luminophores emitted at around 600 nm but their luminescence lifetimes are 160 times different, allowing time-resolved independent analysis. As the fluorescence was enhanced in response to oxidation by hypochlorite and the phosphorescence was sensitive toward oxygen quenching, a four-dimensional relationship between luminescence intensity, fluorescence/phosphorescence ratio, hypochlorite concentration, and oxygen content was established. In cellular imaging, time-resolved photoluminescence imaging microscopy clearly showed the independent fluorescence response toward hypochlorite and phosphorescence response toward oxygen in separated time intervals. This work opens up a new idea for the development of multiplex biosensing and bioimaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Uncarboxylated osteocalcin (GluOC) has been reported to improve glucose metabolism, prevent type 2 diabetes, and decrease the severity of obesity in mice with type 2 diabetes. GluOC can increase glucose uptake in a variety of cells. Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation. We hypothesized that decarboxylated osteocalcin (dcOC), a kind of GluOC, can increase glucose uptake in MG63 cells (osteoblast-like osteosarcoma cells) and influence their proliferation and differentiation., Aim: To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved., Methods: MG63 cells (human osteoblast-like osteosarcoma cells) were treated with dcOC (0, 0.3, 3, 10, or 30 ng/mL) for 1 and 72 h, and glucose uptake was measured by flow cytometry. The effect of dcOC on cell proliferation was measured with a CCK-8 assay, and alkaline phosphatase (ALP) enzyme activity was measured. PI3K was inhibited with LY294002, and hypoxia-inducible factor 1 alpha (HIF-1α) was silenced with siRNA. Then, GPRC6A (G protein-coupled receptor family C group 6 subtype A), total Akt, phosphorylated Akt, HIF-1α, and glucose transporter 1 (GLUT1) levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake., Results: The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term (1 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, P < 0.01; 30 ng/mL group, P < 0.05). Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term (72 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, P < 0.01; 30 ng/mL group, P < 0.05). DcOC triggered Akt phosphorylation in a dose-dependent manner, and the most effective stimulatory concentration of dcOC for short-term (1 h) was 3 ng/mL ( P < 0.01). LY294002 abolished the dcOC-mediated (1 h) promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression. Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α, GLUT1, and Runx2 in a dose-dependent manner. Inhibition of HIF-1α with siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression. DcOC intervention promoted cell proliferation in a time- and dose-dependent manner as determined by the CCK-8 assay. Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h ( P < 0.01)., Conclusion: Short- and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells. This effect may occur through the PI3K/Akt, HIF-1α, and GLUT1 signaling factors., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Citrus folium and its main ingredient nobiletin (NOB) have received widespread attention in recent years due to their antitumor effects. The antitumor effect of Citrus folium is related to the traditional use, mainly in its Chinese medicinal properties of soothing the liver and promoting qi, resolving phlegm, and dispelling stagnation. Some studies have proved that Citrus folium and NOB are more effective for triple-negative breast cancer (TNBC), which is related to the syndrome of stagnation of liver qi. From the perspective of modern biomedical research, NOB has anticancer effects. Its potential molecular mechanisms include inhibition of the cell cycle, induction of apoptosis, and inhibition of angiogenesis, invasion, and migration. Citrus folium and NOB can also reduce the side effects of chemotherapy drugs and reverse multidrug resistance (MDR). However, more research studies are needed to clarify the underlying mechanisms. The modern evidence of Citrus folium and NOB in breast cancer treatment has a strong connection with the traditional concepts and laws of applying Citrus folium in Chinese medicine (CM). As a low-toxic anticancer drug candidate, NOB and its structural changes, Citrus folium , and compound prescriptions will attract scientists to use advanced technologies such as genomics, proteomics, and metabolomics to study its potential anticancer effects and mechanisms. On the contrary, there are relatively few studies on the anticancer effects of Citrus folium and NOB in vivo . The clinical application of Citrus folium and NOB as new cancer treatment drugs requires in vivo verification and further anticancer mechanism research. This review aims to provide reference for the treatment of breast cancer by Chinese medicine., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Yuan Wu et al.)

As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs and their axons, which compose the optic nerve. To functionally restore vision, lost RGCs must be replaced. Despite tremendous advancements in experimental models of optic neuropathy that have elucidated pathways to induce endogenous RGC neuroprotection and axon regeneration, obstacles to achieving functional visual recovery through exogenous RGC transplantation remain. Key challenges include poor graft survival, low donor neuron localization to the host retina, and inadequate dendritogenesis and synaptogenesis with afferent amacrine and bipolar cells. In this review, we summarize the current state of experimental RGC transplantation, and we propose a set of standard approaches to quantifying and reporting experimental outcomes in order to guide a collective effort to advance the field toward functional RGC replacement and optic nerve regeneration.

Three new metal-organic frameworks (MOFs), namely, [Pb 7 (TTPCA) 4 Cl 2 ]·3H 2 O ( 1 ), [Pb 7 (TTPCA) 4 (DMA) 2 (HCOO) 2 ]·H 2 O ( 2 ), and [Pb 4 (TTPCA) 3 ]·3DMF·2H 2 O·H 3 O ( 3 ), were synthesized by the H 3 TTPCA ligand [H 3 TTPCA = 1,1',1″-(1,3,5-triazine-2,4,6-triyl)-tripiperidine-4-carboxylic acid], with lead(II) nitrate under solvothermal conditions. They were characterized by CHN analysis, IR spectroscopy, UV-vis spectroscopy, and single-crystal and powder X-ray diffraction. In addition, their thermogravimetric analysis and fluorescence properties were studied. Compounds 1 - 3 were 3D MOF structures with different Pb x (COO) y clusters: ([Pb 7 (COO) 12 Cl 2 ]), ([Pb 7 (COO) 12 ]), and [Pb 8 (COO) 18 ]. Fluorescence detection of compounds 1 - 3 shows that they can act as excellent sensors of nitrophenols with a low limit of detection and a high quenching constant.

Two trials were designed to investigate the impacts of egg storage time and maternal dietary vitamin E (VE) supplementation on the growth performance and antioxidant capacity of progeny chicks. In total 512 Ross 308 broiler breeder hens (71-wk-old) were assigned to 2 dietary VE treatments (6 and 100 mg/kg) for 14 wk. Progeny chicks used in trials 1 and 2 were originated from eggs laid at week 10 (stored 0 d) and week 8 (stored 14 d), and week 14 (stored 0 d) and week 12 (stored 14 d), respectively. The 4 groups in trial 1 consisted of 2 levels of maternal VE (6 and 100 mg/kg) and 2 egg storage time (0 and 14 d). The 8 groups in trial 2 consisted of 2 levels of maternal VE (6 and 100 mg/kg), 2 egg storage time (0 and 14 d) and progeny sex (male and female). In trial 1, egg storage decreased the body weight, the liver total superoxide dismutase and total antioxidant capacity of 21-day-old offspring (P < 0.05), and the body weight gain and feed intake from 8 to 21 d and 1 to 21 d (P < 0.05); and increased the serum and liver malonaldehyde (MDA) of 7-day-old offspring and the ratio of feed: gain (F/G) from 1 to 7 d (P < 0.05). Maternal VE (100 vs. 6 mg/kg) decreased the F/G from 1 to 7 d and increased the serum total superoxide dismutase of 21-day-old offspring (P < 0.05). In trial 2, egg storage decreased the body weight of 42-day-old offspring, and the body weight gain and feed intake from 22 to 42 d and 1 to 42 d (P < 0.05); and increased the serum and liver MDA of 21- and 42-day-old offspring (P < 0.05). Maternal VE (100 vs. 6 mg/kg) reduced the serum MDA of 7-day-old offspring (P < 0.05). Interactively, maternal VE (100 vs. 6 mg/kg) reduced the serum MDA of offspring originated from stored eggs (P < 0.05), but not for that of offspring originated from unstored eggs in the two trials. It can be concluded that egg storage (14 vs. 0 d) decreased the growth performance and antioxidant capacity of offspring, while maternal dietary VE (100 vs. 6 mg/kg) supplementation could partly alleviate the reduction of antioxidant capacity (except for growth performance) of offspring induced by egg storage for the early phase post-hatch., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Basement membranes help to establish, maintain, and separate their associated tissues. They also provide growth and signaling substrates for nearby resident cells. The internal limiting membrane (ILM) is the basement membrane at the ocular vitreoretinal interface. While the ILM is essential for normal retinal development, it is dispensable in adulthood. Moreover, the ILM may constitute a significant barrier to emerging ocular therapeutics, such as viral gene therapy or stem cell transplantation. Here we take a neurodevelopmental perspective in examining how retinal neurons, glia, and vasculature interact with individual extracellular matrix constituents at the ILM. In addition, we review evidence that the ILM may impede novel ocular therapies and discuss approaches for achieving retinal parenchymal targeting of gene vectors and cell transplants delivered into the vitreous cavity by manipulating interactions with the ILM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This paper presents both inaccuracies and mistakes. Therefore, the article "CircVCAN regulates the proliferation and apoptosis of osteoarthritis chondrocyte through NF-κB signaling pathway, by H.-R. Ma, W.-B. Mu, K.-Y. Zhang, H.-K. Zhou, R.-D. Jiang, L. Cao, published in Eur Rev Med Pharmacol Sci 2020; 24 (12): 6517-6525-DOI: 10.26355/eurrev&#95;202006&#95;21635-PMID: 32633338" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21635.