Floquet Engineering Hz-Level Rabi Spectra in Shallow Optical Lattice Clock.

Quantum metrology with ultrahigh precision usually requires atoms prepared in an ultrastable environment with well-defined quantum states. Thus, in optical lattice clock systems deep lattice potentials are used to trap ultracold atoms. However, decoherence, induced by Raman scattering and higher order light shifts, can significantly be reduced if atomic clocks are realized in shallow optical lattices. On the other hand, in such lattices, tunneling among different sites can cause additional dephasing and strongly broadening of the Rabi spectrum. Here, in our experiment, we periodically drive a shallow ^{87}Sr optical lattice clock. Counterintuitively, shaking the system can deform the wide broad spectral line into a sharp peak with 5.4 Hz linewidth. With careful comparison between the theory and experiment, we demonstrate that the Rabi frequency and the Bloch bands can be tuned, simultaneously and independently. Our work not only provides a different idea for quantum metrology, such as building shallow optical lattice clock in outer space, but also paves the way for quantum simulation of new phases of matter by engineering exotic spin orbit couplings.

Epidemiological characteristics of 17 imported patients infected with SARS-CoV-2 Omicron variant. / 17ä¾‹æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªå¢ƒå¤–è¾“å ¥æ„ŸæŸ“è€ çš„æµè¡Œç— å­¦ç‰¹å¾.

OBJECTIVES: With the continuous generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pressure of epidemic prevention and control continues to increase in China. Omicron with stronger infectiousness, immune escape ability and repeated infection ability spread to many countries and regions around the world in a short period of time. China has also successively reported cases of imported Omicron infections. This study aims to understand the epidemiological characteristics of Omicron variant via analyzing the epidemiological characteristics of imported patients with Omicron in Hunan Province, and to provide reference for preventing and controlling the imported epidemics. METHODS: The clinical data of imported patients with coronavirus disease 2019 admitted to Hunan Province from December 16 to December 31, 2021 were retrospectively collected. The epidemiological information, general information, clinical classification, clinical symptoms, vaccination status, and lung CT were analyzed. Nasopharyngeal swabs and blood samples were collected. Virus nucleic acid was detected by magnetic beads method using SARS-CoV-2 detection kit. Ct values of ORF1ab gene and N gene were compared between asymptomatic infected patients and confirmed patients. The specific IgM and IgG antibodies were detected by chemiluminescence assay using SARS-CoV-2 IgM test kit and SARS-CoV-2 IgG test kit, respectively. Ct values of IgM and IgG antibodies were compared between asymptomatic infected patients and confirmed patients. RESULTS: Seventeen patients with Omicron variant infection were treated in Hunan, including 15 confirmed patients (5 common type and 10 mild type) and 2 asymptomatic infection patients. The 17 patients were all Chinese, they were generally young, and 16 were male. There were 9 patients with diseases. Of them 3 patients had respiratory diseases. All 17 patients had completed the whole process of vaccination, but only one person received a booster shot of SARS-CoV-2 vaccine. The clinical manifestations of the patients were mild, mainly including dry/painful/itchy throat, cough, and fatigue. The total protein and creatine in the asymptomatic infection and confirmed cases infected with Omicron variant were all within the normal range, but other biochemical indicators were abnormal. There were the significant differences in C-reactive protein and fibrinogen between asymptomatic infection and confirmed patients (both P<0.05). There were more patients with elevated C-reactive protein in confirmed patients than without confirmed ones. The detection rate of specific IgM and IgG antibodies on admission was 100%, and there was no significant difference in the specific antibody levels between asymptomatic infection and confirmed patients (P>0.05). There were no significant differences in Ct values of ORF1ab gene and N gene (21.35 and 18.39 vs 19.22 and 15.67) between the asymptomatic infection and the confirmed patients (both P>0.05). Only 3 patients had abnormal lung CT, showing a small amount of patchy and cord-like shadows. One of them had no abnormality on admission but had pulmonary lesions and migratory phenomenon after admission. CONCLUSIONS: The patients with Omicron variant tend to be young people and have milder clinical symptoms, but the viral load is high and the infectiveness is strong. Therefore, the timely identification and effective isolation and control for asymptomatic infections and confirmed patients with mild symptoms are extremely important. In terms of epidemic prevention and control, the government still needs to strengthen the risk control of overseas input, adhere to normalized epidemic prevention and control measures, to effectively control the source of infection, cut off the route of transmission, and protect vulnerable people.

Doubly Modulated Optical Lattice Clock: Interference and Topology.

The quantum system under periodical modulation is the simplest path to understand the quantum nonequilibrium system because it can be well described by the effective static Floquet Hamiltonian. Under the stroboscopic measurement, the initial phase is usually irrelevant. However, if two uncorrelated parameters are modulated, their relative phase cannot be gauged out so that the physics can be dramatically changed. Here, we simultaneously modulate the frequency of the lattice laser and the Rabi frequency in an optical lattice clock (OLC) system. Thanks to the ultrahigh precision and ultrastability of the OLC, the relative phase could be fine-tuned. As a smoking gun, we observed the interference between two Floquet channels. Finally, by experimentally detecting the eigenenergies, we demonstrate the relation between the effective Floquet Hamiltonian and the one-dimensional topological insulator with a high winding number. Our experiment not only provides a direction for detecting the phase effect but also paves a way in simulating the quantum topological phase in the OLC platform.

Clinical characteristics of Graves' disease associated cholestasis. / Gravesç— ç›¸å ³æ€§èƒ†æ±æ·¤ç§¯ç—‡çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: A variety of causes can lead to cholestasis, however, cholestasis caused by Graves' disease is usually overlooked clinically. Here we analyze the clinical characteristics of Graves' disease associated cholestasis so as to have a better understanding for the disease. METHODS: We retrospectively collected 13 inpatients' data who suffered from the Graves' disease associated cholestasis in the Department of Infectious Disease of Xiangya Hospital from January 2000 to December 2018. The characteristics of the patients' age, gender, liver function, thyroid function, coagulation function, the special cardiac examination, treatment, and follow-up data were analyzed. RESULTS: Thirteen patients, including 10 males and 3 females with the age range from 33 to 55 (median 43) years old presented cholestasis, pruritus, and hypermetabolic symptoms. The levels of total bilirubin (TBIL), direct bilirubin (DBIL), glutamic-pyruvic transferase, glutamic-oxaloacetic transferase, alkaline phosphosphatase, and gamma glutamyl transpeptidase were 170.4-976.7 (median 388.8) µmol/L, 93.2-418.1 (median 199.2) µmol/L, 25.1-182.1 (median 106.4) U/L, 38.2-265.7 (median 59.7) U/L, 105.3-332.0 (median 184.5) U/L, and 20.7-345.1 (median 47.6) U/L, respectively. The levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyrotrophin receptor antibody were 4.1-50.0 (median 21.6) pmol/L, 30.4-100.0 (median 87.9) pmol/L, and 4.2-40 (median 19.8) U/mL, respectively. All patients' coagulation function, heart size, and ejection fraction (EF) value were normal. After anti-thyroid treatment, the levels of FT3, FT4, and TBIL decreased. Through telephone interview, we were able to know that after 6 months of anti-thyroid treatment, the level of FT3, FT4, and TBIL in these patients returned to normal, and the itch symptom disappeared completely. CONCLUSIONS: Graves' disease can cause cholestasis, with the low incidence. The symptoms of cholestasis can be improved or even eradicated with the cure of the Graves' disease. The cholestasis may be idiopathic. For patients with cholestasis and hyperthyroidism, Graves' disease should be considered for differential diagnosis.

Upregulation of microRNA-328-3p by hepatitis B virus contributes to THLE-2 cell injury by downregulating FOXO4.

BACKGROUND: Hepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma, and miRNAs play important roles in HBV pathogenesis. Our previous study has shown that miR-328-3p is upregulated in HBV-infected patients and serves as a potent predictor for the prognosis of HBV-related liver failure. METHODS: Here, the role of miR-328-3p in modulating cell injury in HBV-infected liver cells THLE-2 was investigated in detail. MiR-328-3p expression was examined using qRT-PCR. The levels of pro-inflammatory cytokines were measured using ELISA. HBV RNA and HBV DNA levels were quantified. The interactions between STAT3 and miR-328-3p promoter as well as miR-328-3p and FOXO4 were analyzed using chromatin immunoprecipitation (CHIP) assay and luciferase reporter assay, respectively. THLE-2 cell injury was evaluated by examining cell viability and apoptosis. RESULTS: HBV promoted expression of miR-328-3p through the STAT3 signal pathway and that increasingly expressed miR-328-3p downregulated its target FOXO4, leading to the promotion of cell injury in HBV-infected liver cells THLE-2. CONCLUSION: These data demonstrate that HBV-STAT3-miR-328-3p-FOXO4 regulation pathway may play an important role in the pathogenesis of HBV infection.

Predictive role of clinical features in patients with coronavirus disease 2019 for severe disease. / 2019å† çŠ¶ç— æ¯’ç— æ‚£è€ ä¸´åºŠç‰¹å¾å¯¹é‡ç—‡åŒ–çš„é¢„æµ‹ä½œç”¨.

OBJECTIVES: Since the outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly in China and many other countries. The rapid increase in the number of cases has caused widespread panic among people and has become the main public health problem in the world. Severe patients often have difficult breathing and/or hypoxemia after 1 week of onset. A few critically ill patients may not only rapidly develop into acute respiratory distress syndrome, but also may cause coagulopathy, as well as multiple organs failure (such as heart, liver and kidney) or even death. This article is to analyze the predictive role of clinical features in patients with COVID-19 for severe disease, so as to help doctor monitor the severity-related features, restrain the disease progress, and provide a reference for improvement of medical treatment. METHODS: The clinical data of 208 patients with COVID-19 who were isolated and treated in Changsha Public Health Treatment Center from January 17, 2020 to March 14, 2020 were collected. All patients were the mild and ordinary adult patients on admission, including 105 males and 103 females from 19 to 84 (median age 44) years old. According to the "Program for the diagnosis and treatment of novel coronavirus (COVID-19) infected pneumonia (Trial version 7)" issued by the General Office of National Health Committee and Office of State Administration of Traditional Chinese Medicine as the diagnostic and typing criteria. According to progression from mild to severe disease during hospitalization, the patients were divided into a mild group (n=183) and a severe transformation group (n=25). The clinical features such as age, underlying disease, blood routine, coagulation function, blood biochemistry, oxygenation index, and so on were analyzed. Among them, laboratory tests included white blood cell (WBC), lymphocytes (LYM), neutrophil (NEU), hemoglobin (Hb), platelet (PLT), prothrombin time (PT), plasma fibrinogen (Fib), activated partial prothrombin time (APTT), thrombin time (TT), D-dimer, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Cr), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), and oxygen partial pressure in arterial blood. Partial pressure of oxygen in arterial blood/fractional concentration of inspiratory oxygen (PaO2/FiO2) was calculated. The variables with statistical significance were analyzed by logistic regression analysis. RESULTS: Patients in the severe transformation group had more combined underlying diseases than those in the mild group (P<0.05). From the perspective of disease distribution, patients in the severe transformation group had more combined hypertension (P<0.05). In the severe transformation group, PT was significantly longer, the levels of Fib, ALT, AST, CK, LDH, and CRP were significantly higher than those in the mild group (P<0.05 or P<0.001), while LYM, ALB, and PaO2/FiO2 were significantly lower than those in the mild group (P<0.05 or P<0.001). Logistic regression analysis was performed on clinical features with statistically significant differences. Combined with hypertension, LYM, PT, Fib, ALB, ALT, AST, CK, LDH, and CRP as independent variables, and having severe disease or not was the dependent variable. The results show that combined hypertension, decreased LYM, longer PT, and increased CK level were independent risk factors that affected the severity of COVID-19 (P<0.05). CONCLUSIONS: The patients with mild COVID-19 who are apt to develop severe diseases may be related to combined hypertension, decreased LYM, and longer PT, and increased CK level. For the mild patients with these clinical features, early intervention may effectively prevent the progression to severe diseases.

PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by influencing synaptic function in the primary motor cortex of rats.

Proline-rich transmembrane protein 2 (PRRT2) was identified as the causative gene of paroxysmal kinesigenic choreoathetosis (PKC) as well as various other neurological diseases. However, the molecular mechanisms of how mutant PRRT2 leads to abnormal synaptic function and triggers PKC are still obscure. We generated a Prrt2 truncated mutant rat model which shows spontaneous PKC-like attacks with a relative low frequency as well as increased susceptibility to pentylenetetrazol (PTZ)-induced seizures. We demonstrate that PRRT2 is expressed on both pre- and post-synaptic membranes in the M1 cortex. PRRT2 negatively regulates SNARE complex assembly through interaction with SNAP25, STX1A, and VAMP2. In the M1 cortex of the rat model, release of amino acid neurotransmitters is increased. Protein levels of glutamate receptor subunit GRIA1 are significantly increased in PRRT2 mutant rats, while GABA receptor subunits GABRA1 are significantly reduced. Both frequency and amplitude of mEPSC are significantly increased, while amplitude of mIPSC is decreased and the ratio of mEPSC/mIPSC is significantly increased. The balance between excitatory and inhibitory neuronal activity is disrupted, which could lead to abnormal neuronal hyperexcitability. These results provide new insights into the function of PRRT2 in synaptic transmission and movement control, as well as the pathogenic mechanism underlying PKC.

miR-146a-5p enhances hepatitis B virus replication through autophagy to promote aggravation of chronic hepatitis B.

The objective of this study was to investigate the mechanism by which miR-146a-5p mediated autophagy and hepatitis B virus (HBV) replication. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA expression levels of miR-146a-5p and X-linked inhibitor of apoptosis (XIAP) and HBV DNA and RNA. The protein expression levels of XIAP, IκB-α, murine double minute 2 oncoprotein (MDM2) and p53, the phosphorylation of p65, and the conversion of light chain 3 (LC3)-I to LC3-II were detected by Western blotting. The expression levels of XIAP, HBV-related pro-inflammatory cytokines, and serum markers were detected by enzyme-linked immunosorbent assay (ELISA). miR-146a-5p was highly expressed in patients with chronic hepatitis B (CHB) and HBV-expressing hepatocytes. HBV core protein (HBc) and HBV X protein (HBx) were responsible for its effects on miR-146a-5p expression through the nuclear factor-κB pathway. Furthermore, the miR-146a-5p inhibitor suppressed autophagic response and HBV replication as well as MDM2/p53 expression. Luciferase reporter assay confirmed that XIAP was a direct target of miR-146a-5p. We therefore demonstrated that miR-146a-5p mediated positive feedback loop by regulating autophagy-induced HBV replication via targeting the XIAP-mediated MDM2/p53 axis. © 2019 IUBMB Life, 71(9):1336-1346, 2019.

Autophagy protects against retinal cell death in mouse model of cytomegalovirus retinitis.

BACKGROUND: Extensive death of uninfected bystander neuronal cells is an important component of the pathogenesis of cytomegalovirus retinitis (CMV). Our previous results have shown that there is a functional relationship between autophagy and apoptosis during MCMV infection of retinal pigment epithelium (RPE). The purpose of this study was to determine whether autophagy plays a significant role in the death of retinal cells during MCMV retinitis. METHODS: The retinas of adult BALB/c mice were infected with MCMV via supraciliary injection. Rapamycin, a mTOR inhibitor, was injected to MCMV-infected BALB/c mice intraperitoneally. Immunohistochemistry and western blot were performed to observe the spread pattern of virus in retinas and the levels of targeted proteins. Plaque assay was performed to determine the virus titer in different groups. Since Atg5 is a key gene regulating autophagy, we bred Atg5flox/flox; Nestin-Cre mice to deeply elucidate the role of autophagy during MCMV retinitis. Atg5flox/flox; Nestin-Cre mice were genotyped and infected with MCMV. Immunohistochemistry was performed to observe the type of virus-infected cells and apoptosis in retinas during MCMV retinitis. RESULTS: In MCMV mouse model, MCMV infection in outer nuclear layer (ONL) and inner nuclear layer (INL) in the retinas caused cleaved caspase 3 positive apoptosis, which is not co-localized with early antigen (EA) positive virus infected cells in rapamycin treated group. Rapamycin treatment increased the levels of LC3B-II by inhibiting mTOR and decreased the levels of cleaved caspase-3 during MCMV retinitis. However, virus propagation was not affected by rapamycin. In Atg5flox/flox; Nestin-Cre mice, RPE and glial cells were the main targets of viral infection, and number of EA positive retinal cells and TUNEL positive retinal cells was significantly increased compared to Atg5flox/+; Nestin-Cre mice though there was no difference of virus propagation between Atg5flox/flox; Nestin-Cre mice and Atg5flox/+; Nestin-Cre mice. CONCLUSIONS: Autophagy protects retinal cells from MCMV infection induced apoptosis through mTOR-mediated signaling pathway.

Expression of PD1 and BTLA on the CD8+ T Cell and γδT Cell Subsets in Peripheral Blood of Non-Small Cell Lung Cancer Patients.

Objective To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8+ T cells and γδ+ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ+ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. Results The frequency of PD1 on the surfaces of CD8+ T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8+ T cells, rather than on γδ+ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1+ BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1+γδ+ and BTLA+γδ+ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8+ T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8+ T cells and γδ+ T cells, immune escape and tumor invasion.

Inflammation and outer blood-retina barrier (BRB) compromise following choroidal murine cytomegalovirus (MCMV) infections.

Purpose: The purpose of this study was to determine whether the blood-retina barrier is compromised by choroidal murine cytomegalovirus (MCMV) infection, using electron microscopy. Methods: BALB/c mice were immunosuppressed with methylprednisolone and monoclonal antibodies to CD4 and CD8. At several time points post-MCMV intraperitoneal inoculation, the eyes were removed and analyzed with western blotting and immunoelectron microscopy for the presence of MCMV early antigen (EA) and the host protein RIP3. Posterior eyecups from RIP3-/- and RIP3+/+ mice were cultured and inoculated with MCMV. At days 4, 7, and 11 post-infection, cultures were collected and analyzed with plaque assay, immunohistochemical staining, and real-time PCR (RT-PCR). Results: MCMV EA was observed in the nuclei of vascular endothelial cells and pericytes in the choriocapillaris. Disruption of Bruch's membrane was observed, especially at sites adjacent to activated platelets, and a few RPE cells containing some enlarged vesicles were found directly beneath disrupted Bruch's membrane. Some virus particles were also observed in the enlarged vesicles of RPE cells. Levels of the RIP3 protein, which was observed mainly in the RPE cells and the basement membrane of the choriocapillaris, were greatly increased following MCMV infection, while depletion of RIP3 resulted in greatly decreased inflammasome formation, as well as expression of downstream inflammation factors. Conclusions: The results suggest that systemic MCMV spreads to the choroid and replicates in vascular endothelia and pericytes of the choriocapillaris during immunosuppression. Choroidal MCMV infection is associated with in situ inflammation and subsequent disruption of Bruch's membrane and the outer blood-retina barrier.

Interplay of autophagy and apoptosis during murine cytomegalovirus infection of RPE cells.

PURPOSE: Previous studies have demonstrated that autophagy is involved in the pathogenesis of human cytomegalovirus (HCMV) infection. However, whether autophagy is regulated by murine cytomegalovirus (MCMV) infection has not yet been investigated. The purpose of these studies was to determine how autophagy is affected by MCMV infection of the retinal pigment epithelial (RPE) cells and whether there is a functional relationship between autophagy and apoptosis; and if so, how regulation of autophagy impacts apoptosis. METHODS: RPE cells were isolated from C57BL/6 mice and infected with MCMV K181. The cells were cultured in medium containing rapamycin, chloroquine, or ammonium chloride. Green fluorescent protein-light chain 3 (GFP-LC3) plasmid was transfected to RPE cells, and the GFP-LC3 positive puncta were counted. Electron microscopic (EM) images were taken to visualize the structure of the autophagic vacuoles. Western blot was performed to detect the expression of related proteins. Trypan blue exclusion assay was used to measure the percentage of viable cells. RESULTS: Although the LC3B-II levels consistently increased during MCMV infection of RPE cells, administration of chloroquine or ammonium chloride increased LC3B-II expression only at the early stage of infection (6 h post-inoculation [p.i.] and 12 h p.i.), not at or after 24 h p.i. The punctate autophagic vacuoles in the GFP-LC3 transfected RPE cells were counted using light microscopy or by EM examination, the number of autophagic vacuoles was significantly increased in the MCMV-infected RPE cells compared to the uninfected controls. Compared to untreated MCMV-infected control cells, rapamycin treatment resulted in a significant decrease in the cleaved caspase 3 levels as well as a significant decrease in the ratio of phosphorylated mammalian target of rapamycin (mTOR) to total mTOR and in the ratio of phosphorylated P70S6K to total P70S6K. In contrast, chloroquine treatment resulted in a significant increase in the cleaved caspase 3 levels in the MCMV-infected RPE cells. CONCLUSIONS: Autophagic vacuole accumulation was detected during MCMV infection of RPE cells. In contrast, autophagic flux was greatly decreased at or after 24 h p.i. The results suggest that MCMV might have a strategy for inhibiting or blocking autophagy activity by targeting a later autophagy process, such as the formation of autolysosomes or degradation of their content. Our data also suggest that there is a functional relationship between autophagy and apoptosis, which plays an important role during MCMV infection of the RPE.

Gene structure and spatio-temporal expression of chicken LPIN2.

LPIN2 is one of the members of the Lipin family, which acts as a phosphatidate phosphatase enzyme. In this study, we identified the cDNA sequence and exonic variants of chicken LPIN2, and evaluated its spatio-temporal expression patterns. It indicated that chicken LPIN2 cDNA contained a 2,664-bp open reading frame flanked by a 176-bp 5' untranslated region and a 429-bp 3' untranslated region, predicted encoding one protein of 886 amino acids. Fourteen variants (three missense mutations) were detected from the coding region of chicken LPIN2. W265L was predicted to affect the gene function (p < 0.01) and eight synonymous mutations were predicted to affect the binding sites of SR proteins, which suggested the important functions of these variants. Real-time quantitative PCR revealed that LPIN2 in two genotypic chickens (LD and HB chickens, with difference in growth rate) presented similar tissue expression patterns, which was liver and ovary enriched with low abundance in skeleton muscles. Chicken LPIN2 exhibited tissue-specific temporal-expression patterns during postnatal development (0-16 weeks). Chicken cutaneous LPIN2 was in steady-state mRNA levels during postnatal development; chicken LPIN2 mRNA in pectoralis major had a prominent level at 0 week-old, then dropped dramatically at 4 week-old and maintained a relatively low level through 4-16 weeks; while chicken hepatic LPIN2 had a relatively high expression at 0 week-old, with a relatively low level through 4-12 weeks and a slight increase at 16 week-old. The studies about the basic gene features of chicken LPIN2 would lay the foundation for further exploring its biological function.

Research on universal combinatorial coding.

The conception of universal combinatorial coding is proposed. Relations exist more or less in many coding methods. It means that a kind of universal coding method is objectively existent. It can be a bridge connecting many coding methods. Universal combinatorial coding is lossless and it is based on the combinatorics theory. The combinational and exhaustive property make it closely related with the existing code methods. Universal combinatorial coding does not depend on the probability statistic characteristic of information source, and it has the characteristics across three coding branches. It has analyzed the relationship between the universal combinatorial coding and the variety of coding method and has researched many applications technologies of this coding method. In addition, the efficiency of universal combinatorial coding is analyzed theoretically. The multicharacteristic and multiapplication of universal combinatorial coding are unique in the existing coding methods. Universal combinatorial coding has theoretical research and practical application value.

Sialic Acids Blockade-Based Chemo-Immunotherapy Featuring Cancer Cell Chemosensitivity and Antitumor Immune Response Synergies.

Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma: A case report and review of literature.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged female with primary large cell NEC (LCNEC) of the common hepatic duct combined with distal cholangiocarcinoma (dCCA). Additionally, after a review of the relevant literature, we summarize and compare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease. CASE SUMMARY: A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months. Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign. Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels. Imaging examination revealed a 1-cm tumour in the middle and lower segments of the common bile duct. Pancreaticoduodenectomy + lymph node dissection was performed, and hepatic duct tumours were unexpectedly found during surgery. Pathology suggested poorly differentiated LCNEC (approximately 0.5 cm × 0.5 cm × 0.4 cm), Ki-67 (50%), synaptophysin+, and chromogranin A+. dCCA pathology suggested moderately differentiated adenocarcinoma. The patient eventually developed lymph node metastasis in the liver, bone, peritoneum, and abdominal cavity and died 24 months after surgery. Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours. CONCLUSION: The prognosis of MiNEN and pure NEC alone is different, and the selection of treatment options needs to be differentiated.

Low trichorhinophalangeal syndrome 1 gene transcript levels in basal-like breast cancer associate with mesenchymal-to-epithelial transition.

OBJECTIVE: To investigate trichorhinophalangeal syndrome 1 gene (TRPS-1) expression patterns in different subtypes of breast cancer and its correlations with other genes and survival using microarray data sets. METHODS: The transcripts of TRPS-1 and its role in survival in breast cancer were analyzed using published microarray data sets#x02014;Netherlands Cancer Institute (NKI) cohort and Wang cohort. RESULTS: TRPS-1 expression was lower in basal-like breast cancer. The mRNA levels of TRPS-1 negatively correlated with Slug (Pearson correlation coefficient=-0.1366, P=0.0189 in NKI data set and Pearson correlation coefficient=-0.1571, P=0.0078 in Wang data set), FOXC1 (Pearson correlation coefficient=-0.1211, P=0.0376 in NKI data set and Pearson correlation coefficient=-0.1709, P=0.0037 in Wang data set), and CXCL1 (Pearson correlation coefficient=-0.1197, P=0.0399 in NKI data set and Pearson correlation coefficient=-0.3436, P<0.0001 in Wang data set), but positively correlated with BRCA1 (Pearson correlation coefficient=0.1728, P=0.0029 in NKI data set and Pearson correlation coefficient=0.1805, P=0.0022 in Wang data set). Low TRPS-1 expression associated with poor overall survival (hazard ratio 1.79, 95% CI of ratio 0.9894 to 3.238, P=0.054) and relapse-free survival (hazard ratio 1.913, 95% CI of ratio 1.159 to 3.156, P<0.05). The low TRPS-1 mRNA levels predicted poor outcome in breast cancer patients by the 70-gene signature. CONCLUSION: The strong expression of TRPS-1 may serve as a good prognostic marker in breast cancer.

Tra2ß Enhances Cell Proliferation by Inducing the Expression of Transcription Factor SP1 in Cervical Cancer.

Objective: In this study, the role and potential mechanism of transformer 2ß (Tra2ß) in cervical cancer were explored. Methods: The transcriptional data of Tra2ß in patients with cervical cancer from Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases were investigated. The functions of Tra2ß were evaluated by using Western blot, MTT, colony formation, Transwell assays, and nude mouse tumor formation experiments. Target genes regulated by Tra2ß were studied by RNA-seq. Subsequently, representative genes were selected for RT-qPCR, confocal immunofluorescence, Western blot, and rescue experiments to verify their regulatory relationship. Results: The dysregulation of Tra2ß in cervical cancer samples was observed. Tra2ß overexpression in Siha and Hela cells enhanced cell viability and proliferation, whereas Tra2ß knockdown showed the opposite effect. Alteration of Tra2ß expression did not affect cell migration and invasion. Furthermore, tumor xenograft models verified that Tra2ß promoted cervical cancer growth. Mechanically, Tra2ß positively regulated the mRNA and protein level of SP1, which was critical for the proliferative capability of Tra2ß. Conclusion: This study demonstrated the important role of the Tra2ß/SP1 axis in the progression of cervical cancer in vitro and in vivo, which provides a comprehensive understanding of the pathogenesis of cervical cancer.

Econazole selectively induces cell death in NF1-homozygous mutant tumor cells.

Cutaneous neurofibromas (cNFs) are tumors that develop in more than 99% of individuals with neurofibromatosis type 1 (NF1). They develop in the dermis and can number in the thousands. cNFs can be itchy and painful and negatively impact self-esteem. There is no US Food and Drug Administration (FDA)-approved drug for their treatment. Here, we screen a library of FDA-approved drugs using a cNF cell model derived from human induced pluripotent stem cells (hiPSCs) generated from an NF1 patient. We engineer an NF1 mutation in the second allele to mimic loss of heterozygosity, differentiate the NF1+/- and NF1-/- hiPSCs into Schwann cell precursors (SCPs), and use them to screen a drug library to assess for inhibition of NF1-/- but not NF1+/- cell proliferation. We identify econazole nitrate as being effective against NF1-/- hiPSC-SCPs. Econazole cream selectively induces apoptosis in Nf1-/- murine nerve root neurosphere cells and human cNF xenografts. This study supports further testing of econazole for cNF treatment.

Tumor-Associated Extracellular Microvesicles with Fluorine-Modified Carbohydrate Antigens Trigger a Stronger Antitumor Immune Response.

Abnormal glycosylation is a hallmark of tumor development, and tumor-associated carbohydrate antigens are potential immune targets for tumor therapy. Tumor-associated extracellular microvesicles are subcellular vesicles released from cell membranes that have immunogenicity similar to that of precursor cells. However, unmodified tumor-derived microvesicles have weaknesses, such as low immunogenicity, poor biostability, and short half-life in vivo. For the first time, we herein generated extracellular microvesicles containing modified tumor-associated carbohydrate antigens by constructing a cell line with highly expressed antigen-processing enzymes utilizing fluorine-modified monosaccharide substrates via a metabolic oligosaccharide engineering strategy. The microvesicles were applied to tumor immunity, achieving enhanced immunoprophylaxis and immunotherapy effects. Furthermore, the mechanisms of antitumor immunity were explored. Our findings may provide new insights into the adhibition of suitably modified extracellular microvesicles and the development of more effective carbohydrate-based anticancer vaccines.