[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

Matrix-degrading soft-nanoplatform with enhanced tissue penetration for amplifying photodynamic therapeutic efficacy of breast cancer.

The dense extracellular matrix (ECM) in the tumor microenvironment forms an abnormal physical barrier, which impedes the delivery and penetration of nanomedicines and hinders their therapeutic efficacy. Herein, we synthesize matrix-degrading soft-nanocapsules composed of human serum albumin (HSA) and hyaluronidase (HAase) for overcoming the obstruction of ECM in the tumor microenvironment. The matrix-degrading human serum albumin/hyaluronidase soft-nanocapsules, referred to as HSA/HAase SNCs, possess a uniform diameter, inward hollow structure, and wrinkled morphology. In vitro biocompatibility results indicate that the HSA/HAase SNCs display no adverse effects on the viability of human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs), and mouse breast cancer (4T1) cells and do not induce hemolysis towards red blood cells (RBCs). The HSA/HAase SNCs exhibit a 1.4-fold increase in tumor cellular uptake compared to the stiff-counterparts and enhanced penetration in 4T1-, mouse colon carcinoma 26- (CT26-), and mouse pancreatic cancer- (PanO2-) multicellular spheroids. Thanks to the advanced biological properties, a photodynamic platform prepared by loading Ce6 in the HSA/HAase SNCs (HSA/HAase@Ce6) shows improved reactive oxygen species production, a stronger killing effect for cancer cells, and deeper penetration in tumor tissues. In vivo experiments show that HSA/HAase@Ce6 effectively inhibits tumor growth in breast cancer mouse models. RNA-seq analysis of the mice that received the treatment of HSA/HAase@Ce6 shows enrichment of signaling pathways associated with ECM-degradation, which demonstrates that the matrix-degrading nanocapsules overcome the ECM-induced physical barriers in tumors. Overall, the matrix-degrading soft-nanoplatform represents a highly promising strategy to overcome ECM-induced physical barriers and enhance the therapeutic efficacy of nanomedicines.

Cholecystokinin-expressing superficial tufted cells modulate odour representation in the olfactory bulb and olfactory behaviours.

In mammals, odour information within the olfactory bulb (OB) is processed by complex neural circuits before being ultimately represented in the action potential activity of mitral/tufted cells (M/Ts). Cholecystokinin-expressing (CCK+) superficial tufted cells (sTCs) are a subset of tufted cells that potentially contribute to olfactory processing in the OB by orchestrating M/T activity. However, the exact role of CCK+ sTCs in modulating odour processing and olfactory function in vivo is largely unknown. Here, we demonstrate that manipulating CCK+ sTCs can generate perception and induce place avoidance. Optogenetic activation/inactivation of CCK+ sTCs exerted strong but differing effects on spontaneous and odour-evoked M/T firing. Furthermore, inactivation of CCK+ sTCs disrupted M/T odour encoding and impaired olfactory detection and odour discrimination. These results establish the role of CCK+ sTCs in odour representation and olfactory behaviours. KEY POINTS: Mice could perceive the activity of CCK+ sTCs and show place avoidance to CCK+ sTC inactivation. Optical activation of CCK+ sTCs increased the percentage of cells with odour response but reduced the odour-evoked response in M/Ts in awake mice. Optical inactivation of CCK+ sTCs greatly decreased spontaneous firing and odour-evoked response in M/Ts. Inactivation of CCK+ sTCs impairs the odour decoding performance of M/Ts and disrupts odour detection and discrimination behaviours in mice. These results indicate that CCK+ sTCs participate in modulating the odour representation and maintaining normal olfactory-related behaviours.

Clinical efficacy of intradermal type I collagen injections in treating skin photoaging in patients from high-altitude areas.

BACKGROUND: Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like Yunnan Province. Intradermal Col Ι injections stimulate collagen production, potentially improving skin quality. This study aims to assess the efficacy and safety of this treatment for photoaging. AIM: To evaluate the efficacy and safety of intradermal type Ι collagen (Col Ι) injection for treating photoaging. METHODS: This prospective, self-controlled study investigated the impact of intradermal injections of Col Ι on skin photodamage in 20 patients from the Yunnan Province. Total six treatment sessions were conducted every 4 wk ± 3 d. Before and after each treatment, facial skin characteristics were quantified using a VISIA skin detector. Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector. The Face-Q scale was used for subjective evaluation of the treatment effect by the patients. RESULTS: The skin thickness of the right cheek consistently increased after each treatment session compared with baseline. The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline. The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions, whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions. The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline (P < 0.05). These findings were also supported by skin ultrasound images. The feature count for the red areas and wrinkle feature count decreased following the treatment (P < 0.05). VISIA assessments also revealed a decrease in the red areas after treatment. The Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session. The overall appearance of the patients improved after treatment. CONCLUSION: Intradermal Col Ι injection improves photoaging, with higher patient satisfaction and fewer adverse reactions, and could be an effective treatment method for populations residing in high-altitude areas.

Magnetic CoFe hydrotalcite composite Co metal-organic framework material efficiently activating peroxymonosulfate to degrade sulfamethoxazole: Oxygen vacancy-mediated radical and non-radical pathways.

Herein, a novel rich oxygen vacancy (Ov) cobalt-iron hydrotalcite composite cobalt metal-organic framework material (ZIF-67/CoFe-LDH) was prepared by simple urea water and heat reduction approach and utilized for the peroxymonosulfate (PMS) system to remove sulfamethoxazole (SMX). 95 ± 1.32 % SMX (20 mg/L) was able to degraded in 20 min with TOC removal of 53 ± 1.56 % in ZIF-67/CoFe-LDH/PMS system. The system maintained a fantastic catalytic capability with wide pH range (3-9) and common interfering substances (Cl-, NO3-, CO32-, PO42- and humic acid (HA)), and the degradation efficiency could even remain 80.2 ± 1.48 % at the fifth cycle. Meanwhile, the applicability and feasibility of the catalysts for practical water treatment was verified by the degradation effects of SMX in different water environments and several other typical pollutants. Co and Fe bimetallic active centers synergistically activate PMS, and density functional theory (DFT) predicted adsorption energy about Ov in ZIF-67/CoFe-LDH for PMS was 1.335 eV, and OO bond length of PMS was stretched to 1.826 Å. As a result, PMS was more easily activated and broken, which accelerated the singlet oxygen (1O2), sulfate radical (SO4•-), high-valent metals and other reactive oxygen species (ROS). Radical and non-radical jointly degrading the pollutants improved the catalytic effect. Finally, SMX degradation intermediates were analyzed to explain the degradation pathway and their biotoxicity was also evaluated. This paper provides a new research perspective of oxygen vacancy activating PMS to degrade pollutants.

Simultaneous Biofilm Disruption, Bacterial Killing, and Inflammation Elimination for Wound Treatment Using Silver Embellished Polydopamine Nanoplatform.

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

Cross-cultural experiences and self-development: a psychobiographical study of Bruce Lee.

A common challenge people face in today's cross-cultural world is how to solve a series of adaptation problems caused by cultural conflict. Exploring Bruce Lee's successful cross-cultural experiences through psychobiography offers some inspiration and thoughts. How did Bruce Lee successfully integrate martial arts, symbolising the Eastern culture, with films representing the Western culture, finally propelling kung fu films onto the international stage? Numerous publicly available materials about Bruce Lee were collected for this study, and the research data were evaluated using thematic analysis. Bruce Lee's success benefitted from reconstructing cultural environment information and exercising his initiative to shape a new cultural environment. His life experiences reflect individual cognition behaviour and social and cultural environments as two aspects of a dynamic circulation system and show that the two have reached internal and spiralling harmony through mutual integration. In the context of the Oriental collectivism culture's family narrative, Chinese adults' personality development features the unique theme of 'inheritance and innovation'. Dealing with the relationship between self-actualisation and familism is another important and challenging task in developing the Chinese personality.

Developmental Shifts in the Microbiome of a Cosmopolitan Pest: Unraveling the Role of Wolbachia and Dominant Bacteria.

Wolbachia bacteria (phylum Proteobacteria) are ubiquitous intracellular parasites of diverse invertebrates. In insects, coevolution has forged mutualistic associations with Wolbachia species, influencing reproduction, immunity, development, pathogen resistance, and overall fitness. However, the impact of Wolbachia on other microbial associates within the insect microbiome, which are crucial for host fitness, remains less explored. The diamondback moth (Plutella xylostella), a major pest of cruciferous vegetables worldwide, harbors the dominant Wolbachia strain plutWB1, known to distort its sex ratio. This study investigated the bacterial community diversity and dynamics across different developmental life stages and Wolbachia infection states in P. xylostella using high-throughput 16S rDNA amplicon sequencing. Proteobacteria and Firmicutes dominated the P. xylostella microbiome regardless of life stage or Wolbachia infection. However, the relative abundance of dominant genera, including an unclassified genus of Enterobacteriaceae, Wolbachia, Carnobacterium, and Delftia tsuruhatensis, displayed significant stage-specific variations. While significant differences in bacterial diversity and composition were observed across life stages, Wolbachia infection had no substantial impact on overall diversity. Nonetheless, relative abundances of specific genera differed between infection states. Notably, Wolbachia exhibited a stable, high relative abundance across all stages and negatively correlated with an unclassified genus of Enterobacteriaceae, Delftia tsuruhatensis, and Carnobacterium. Our findings provide a foundational understanding of the complex interplay between the host, Wolbachia, and the associated microbiome in P. xylostella, paving the way for a deeper understanding of their complex interactions and potential implications for pest control strategies.

Enhancing Dendritic Cell Activation Through Manganese-Coated Nanovaccine Targeting the cGAS-STING Pathway.

Background: Nanovaccines have emerged as a promising vaccination strategy, exhibiting their capacity to deliver antigens and adjuvants to elicit specific immune responses. Despite this potential, optimizing the design and delivery of nanovaccines remains a challenge. Methods: In this study, we engineered a dendritic mesoporous silica-based nanocarrier enveloped in a metal-phenolic network (MPN) layer containing divalent manganese ions and tannic acid (MSN@MT). This nanocarrier was tailored for antigen loading to serve as a nanovaccine, aiming to activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in dendritic cells (DCs). Our experimental approach encompassed both cellular assays and mouse immunizations, allowing a comprehensive evaluation of the nanovaccine's impact on DC activation and its influence on the generation of antigen-specific T-cell responses. Results: MSN@MT demonstrated a remarkable enhancement in humoral and cellular immune responses in mice compared to control groups. This highlights the potential of MSN@MT to effectively trigger the cGAS-STING pathway in DCs, resulting in robust immune responses. Conclusion: Our study introduces MSN@MT, a unique nanocarrier incorporating divalent manganese ions and tannic acid, showcasing its exceptional ability to amplify immune responses by activating the cGAS-STING pathway in DCs. This innovation signifies a stride in refining nanovaccine design for potent immune activation.

Direct interaction of platelet with tumor cell aggravates hepatocellular carcinoma metastasis by activating TLR4/ADAM10/CX3CL1 axis.

Metastasis is the main culprit of cancer-related death and account for the poor prognosis of hepatocellular carcinoma. Although platelets have been shown to accelerate tumor cell metastasis, the exact mechanism remained to be fully understood. Here, we found that high blood platelet counts and increased tumor tissue ADAM10 expression indicated the poor prognosis of HCC patients. Meanwhile, blood platelet count has positive correlation with tumor tissue ADAM10 expression. In vitro, we revealed that platelet increased ADAM10 expression in tumor cell through TLR4/NF-κB signaling pathway. ADAM10 catalyzed the shedding of CX3CL1 which bound to CX3CR1 receptor, followed by inducing epithelial to mesenchymal transition and activating RhoA signaling in cancer cells. Moreover, knockdown HCC cell TLR4 (Tlr4) or inhibition of ADAM10 prevented platelet-increased tumor cell migration, invasion and endothelial permeability. In vivo, we further verified in mice lung metastatic model that platelet accelerated tumor metastasis via cancer cell TLR4/ADAM10/CX3CL1 axis. Overall, our study provides new insights into the underlying mechanism of platelet-induced HCC metastasis. Therefore, targeting the TLR4/ADAM10/CX3CL1 axis in cancer cells hold promise for the inhibition of platelet-promoted lung metastasis of HCC.

Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis.

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.

Nanovaccine-based strategies for lymph node targeted delivery and imaging in tumor immunotherapy.

Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce tumor regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific and adverse side effects. However, the challenge in the field of therapeutic tumor vaccines is ensuring the delivery of immune components to the lymph nodes (LNs) to activate immune cells. The clinical response rate of traditional therapeutic tumor vaccines falls short of expectations due to inadequate lymph node delivery. With the rapid development of nanotechnology, a large number of nanoplatform-based LN-targeting nanovaccines have been exploited for optimizing tumor immunotherapies. In addition, some nanovaccines possess non-invasive visualization performance, which is benefit for understanding the kinetics of nanovaccine exposure in LNs. Herein, we present the parameters of nanoplatforms, such as size, surface modification, shape, and deformability, which affect the LN-targeting functions of nanovaccines. The recent advances in nanoplatforms with different components promoting LN-targeting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies to both improve targeting performance and enhance the quality of LN imaging are discussed. Finally, we summarize the prospects and challenges of nanoplatform-based LN-targeting and /or imaging strategies, which optimize the clinical efficacy of nanovaccines in tumor immunotherapies.

Effects of Antibiotic Treatment on the Development and Bacterial Community of the Wolbachia-Infected Diamondback Moth.

Based on the important role of antibiotic treatment in the research of the interaction between Wolbachia and insect hosts, this study aimed to identify the most suitable antibiotic and concentration for Wolbachia elimination in the P. xylostella, and to investigate the effect of Wolbachia and antibiotic treatment on the bacterial community of P. xylostella. Our results showed that the Wolbachia-infected strain was plutWB1 of supergroup B in the P. xylostella population collected in Nepal in this study; 1 mg/mL rifampicin could remove Wolbachia infection in P. xylostella after 1 generation of feeding treatment and the toxic effect was relatively low; among the 29 samples of adult P. xylostella in our study (10 WU samples, 10 WA samples, and 9 WI samples), 52.5% of the sequences were of Firmicutes and 47.5% were of Proteobacteria, with the dominant genera being mainly Carnobacterium (46.2%), Enterobacter (10.1%), and Enterococcus (6.2%); Moreover, antibiotic removal of Wolbachia infection in P. xylostella and transfer to normal conditions for 10 generations no longer significantly affected the bacterial community of P. xylostella. This study provides a theoretical basis for the elimination method of Wolbachia in the P. xylostella, as well as a reference for the elimination method of Wolbachia in other Wolbachia-infected insect species, and a basis for the study of the extent and duration of the effect of antibiotic treatment on the bacterial community of the P. xylostella.

Pan-Cancer Study of the Prognosistic Value of Selenium Phosphate Synthase 1.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase (SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity.Methods: The expression of selenophosphate synthase 1 (SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression.Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC (P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC.Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

Diversity of Wolbachia infection and its influence on mitochondrial DNA variation in the diamondback moth, Plutella xylostella.

Plutella xylostella is a pest that severely damages cruciferous vegetables worldwide and has been shown to be infected with the maternally inherited bacteria Wolbachia, with the main infected strain was plutWB1. In this study, we performed a large-scale global sampling of P. xylostella and amplified 3 mtDNA genes of P. xylostella and 6 Wolbachia genes to analyze the infection status, diversity of Wolbachia in P. xylostella, and its effect on mtDNA variation in P. xylostella. This study provides a conservative estimate of Wolbachia infection rates in P. xylostella, which was found to be 7% (104/1440). The ST 108 (plutWB1) was shared among butterfly species and the moth species P. xylostella, revealing that Wolbachia strain plutWB1 acquisition in P. xylostella may be through horizontal transmission. The Parafit analyses indicated a significant association between Wolbachia and Wolbachia-infected P. xylostella individuals, and individuals infected with plutWB1 tended to cluster in the basal positions of the phylogenetic tree based on the mtDNA data. Additionally, Wolbachia infections were associated with increased mtDNA polymorphism in the infected P. xylostella population. These data suggest that Wolbachia endosymbionts may have a potential effect on mtDNA variation of P. xylostella.

Carrier type affects anammox community assembly, species interactions and nitrogen conversion.

The impacts of carrier type on anammox community assembly, species interactions and nitrogen conversion were studied in this work. It was found that in addition to shared species with higher abundance, different carrier types recruited rare species by imposing selection pressure. Results from co-occurrence networks revealed that carrier type strongly influenced interactions between keystone species inhabiting within anammox biofilm through potentially inducing niche differences. Overall, elastic cubic sponges would lead to closer cooperation between different populations, whereas plastic hollow cylinders would trigger fiercer competition. Meanwhile, the results based on metagenomics sequencing showed carrier type significantly affected nitrogen conversion related genes abundances, and higher reads number was detected on the elastic cubic sponges. The information obtained in this work could provide some valuable information for the selection and optimization of carrier type in the anammox process.

Clinicopathological Features and Survival for Low ER-positive Breast-cancer Patients.

Context: Testing patients for estrogen-receptor (ER) expression has become an important factor in the prognosis and prediction of breast cancer. Many studies have shown that endocrine therapy has no benefit for breast-cancer patients with low ER (ER+) expression, in which the proportion of positively stained cells is 1% to 9%. Objective: The study intended to explore the response to endocrine therapy of ER+ breast-cancer patients and to evaluate the benefits of the clinical use of endocrine therapy for treatment. Design: The research team designed a retrospective analysis and reviewed the data and survival rates of patients with early breast cancer. Setting: The study took place at the Hebei Breast Disease Clinic at the Fourth Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Eligible participants in the study were 862 patients were diagnosed at and admitted to the clinic with early, nonadvanced breast cancer between January and December 2012. Outcome Measures: Based on ER-expression levels, participants were divided into ER negative (ER-), which indicates no positive staining of cells; ER+; and ER positive (ER++)-high expression in which the proportion of positively stained cells is ≥10%. The clinicopathological characteristics and the survival rates of the three groups were compared. Results: The clinicopathological features were similar for the ER- and ER+ groups. Compared to participants in the ER++ group, participants in the ER+ group: (1) were in an earlier stage, (2) had larger tumors, (3) were more likely to be positive for human epidermal growth factor receptor-2 (HER-2), (4) had a higher expression rate of Ki-67, (5) had a lower progesterone-receptor (PR) expression rate, (6) were more likely to receive chemotherapy, and (7) were less likely to receive endocrine therapy. Regardless of whether a participant received endocrine therapy or not, the seven-year overall survival (OS) between the ER- group and the ER+ group showed no significant difference, but both were in a worse condition than the ER++ group (P = .026). Conclusions: The current study found that the clinicopathological features of ER+ breast cancers were different from those of ER++ breast cancers and similar to those of ER-negative breast cancers. The benefits of endocrine therapy for ER+ breast-cancer patients weren't obvious.

DFT investigation on the carbonate radical formation in the system containing carbon dioxide and hydroxyl free radical.

A density functional theory (DFT) study was performed to explore the reaction mechanisms of CO2-containing systems(CO2,HCO3-,H2CO3) with hydroxyl radical using UM06-2X/aug-cc-pVTZ for geometry optimization and UCCSD(T)-F12/cc-pVDZ-F12 for electronic energies, the effect of solvation is considered using the implicit solvent model with two explicit water molecule. The final transformation of hydroxyl radical into carbonate anion radical by reaction with CO2-containing system was studied. The energy barriers, Gibbs free energy, reaction enthalpy changes and reaction rate constants for reaction of CO2-containing systems by hydroxyl radical are calculated. The results show that the reaction of hydroxyl with HCO3- has the lowest energy barrier (5.6 kcal/mol) and maximum reaction rate constant (7.60 × 107dm3mol-1s-1). However, the reaction of hydroxyl radical with CO2 has the highest energy barrier (20.3 kcal/mol) and the minimum reaction rate constant (8.88 × 10-10 dm3mol-1s-1) respectively. The equilibrium constant and rate ratio were calculated by the concentration ratio and free energy of the two conformations of H2CO3 in aqueous solution. The results show that the cc conformation of carbonate has a little higher reaction energy barrier and a higher reaction rate than ct conformation. ∙HCO3 generated by the reaction of CO2 and H2CO3 with hydroxyl radical is further dissociated in aqueous solution to form carbonate radical anion. The calculated free energy of the dissociation process is -2.5 kcal/mol and pKa is -1.9, indicating that HCO3- is a strong acid. Therefore, hydroxyl radicals are spontaneously converted to carbonate radical anions in CO2-containing systems.

A congenital CMV infection model for follow-up studies of neurodevelopmental disorders, neuroimaging abnormalities, and treatment.

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.