N-linked glycoproteins and host proteases are involved in swine acute diarrhea syndrome coronavirus entry.

IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.

DFT investigation of the DDQ-catalytic mechanism for constructing C-O bonds.

In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model. The computational results indicated that DDQ, serving as a photo-catalyst, would be excited under visible light of 450 nm, aligning well with experimental observations as reflected in the UV-vis spectrum. Gibbs free energy surface analyses of the three reactions suggested that the path involving 3DDQ* activating the reactant (-COOH, H2O, or CH3OH) is favorable. Additionally, the role of O2 was investigated, revealing that it could facilitate the recycling of DDQ by lowering the energy barrier for the conversion of the DDQH˙ radical (not DDQH2) into DDQ. The use of ρhole and ρele can reveal the photo-catalytic reaction and charge transfer processes, while localized orbital locator isosurfaces and electron spin density isosurface graphs were employed to analyze structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes, shedding light on the mechanisms governing C-O bond formation from arenes catalyzed by DDQ.

Outcomes in pediatric extracorporeal cardiopulmonary resuscitation: A single-center retrospective study from 2007 to 2022 in China.

OBJECTIVE: We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: The retrospective study included a total of 77 pediatric cases (7 neonates and 70 children) who underwent ECPR after in-hospital and out-of-hospital cardiac arrest between July 2007 and December 2022. Primary endpoints were complications, while secondary endpoints included all-cause in-hospital mortality. RESULTS: Among the 45 cases experiencing complications, 4 neonates and 41 children had multiple simultaneous complications, primarily neurological issues in 25 cases. Additionally, organ failure occurred in 11 cases, and immunodeficiency was present in two cases. Furthermore, 9 cases experienced bleeding events, and 13 cases showed thrombosis. Patients with complications had lower weight, shorter ECMO durations, and longer CPR durations. Non-survivors had longer CPR durations and shorter durations of ECMO, ICU stay, and mechanical ventilation compared to survivors. Complications were more prevalent in non-survivors, particularly organ failure and bleeding events. CONCLUSION: Weight, CPR duration, and ECMO duration were associated with complications, suggesting areas for treatment optimization. The higher occurrence of complications in non-survivors underscores the importance of early detection and management to improve survival rates. Our findings suggest clinicians consider these factors in prognostic assessments to enhance the effectiveness of ECPR programs.

Low-dose nifedipine rescues impaired endothelial progenitor cell-mediated angiogenesis in diabetic mice.

It is of great clinical significance to develop potential novel strategies to prevent diabetic cardiovascular complications. Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic vascular complications. In the present study we evaluated whether low-dose nifedipine could rescue impaired EPC-mediated angiogenesis and prevent cardiovascular complications in diabetic mice. Diabetes was induced in mice by five consecutive injections of streptozotocin (STZ, 60 mg·kg-1·d-1, i.p.). Diabetic mice were treated with low-dose nifedipine (1.5 mg·kg-1·d-1, i.g.) for six weeks. Then, circulating EPCs in the peripheral blood were quantified, and bone marrow-derived EPCs (BM-EPCs) were prepared. We showed that administration of low-dose nifedipine significantly increased circulating EPCs, improved BM-EPCs function, promoted angiogenesis, and reduced the cerebral ischemic injury in diabetic mice. Furthermore, we found that low-dose nifedipine significantly increased endothelial nitric oxide synthase (eNOS) expression and intracellular NO levels, and decreased the levels of intracellular O2.- and thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) in BM-EPCs of diabetic mice. In cultured BM-EPCs, co-treatment with nifedipine (0.1, 1 µM) dose-dependently protected against high-glucose-induced impairment of migration, and suppressed high-glucose-induced TSP-1 secretion and superoxide overproduction. In mice with middle cerebral artery occlusion, intravenous injection of diabetic BM-EPCs treated with nifedipine displayed a greater ability to promote local angiogenesis and reduce cerebral ischemic injury compared to injection of diabetic BM-EPCs treated with vehicle, and the donor-derived BM-EPCs homed to the recipient ischemic brain. In conclusion, low-dose nifedipine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in diabetic mice. It is implied that chronic treatment with low-dose nifedipine may be a safe and economic manner to prevent ischemic diseases (including stroke) in diabetes.

[Myrislignan Induces Apoptosis in Gastric Cancer Cell Line Through PI3K/AKT Signaling Pathway].

Objective: To investigate the effect of myrislignan (MYR) on the apoptosis of gastric cancer cell line and its relationship with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods: The gastric cells (SGC-7901) were treated with MYR at different concentrations, i.e., 0, 25, 50, 100, and 200 µmol/L, for 48 h and 72 h and the effect of MYR on the proliferation of SGC-7901 cells was measured by CCK-8 assay. Then, SGC-7901 cells were treated with different concentrations of MYR at 50, 100, and 200 µmol/L for 48 h. Meanwhile, a normal control group and a dimethyl sulfoxide (DMSO) solvent control group (0.1% DMSO) were established. Flow cytometry was used to determine the apoptosis rate of SGC-7901 cells. The protein expression levels of PI3K, AKT, Bcl-2-associated X protein (BAX), cysteine-dependent aspartate-specifc protease-3 (Caspase-3), and Caspase-9 were determined by Western blot. Then, PI3K activator (20 µmol/mL) was used to treat SGC-7901 cells for 48 h in 4 groups, the control group, 0.1% DMSO group, MYR group, and MYR+PI3K activator group, and the effect on MYR's induction of apoptosis and regulation of the protein expression levels of PI3K, AKT, BAX, Caspase-3, and Caspase-9 in SGC-7901 cells. Results: Compared with the control group, MYR at 50, 100 and 200 µmol/L inhibited the proliferation of gastric cancer cells, increased the apoptosis rate, down-regulated the protein expression levels of PI3K and AKT, and up-regulated the protein expression levels of BAX, Caspase-3, and Caspase-9 in a dose-dependent manner ( P<0.05). However, PI3K activator attenuated MYR-induced apoptosis in gastric cancer cells and MYR's regulation of PI3K, AKT, BAX, Caspase-3, and Caspase-9 protein expression ( P<0.05). Conclusion: MYR induces the expression of BAX, Caspase-3, and Caspase-9 proteins by inhibiting the PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer cells.

[Effect of ligustrazine on hypoxic-ischemic encephalopathy in neonatal rats by regulating autophagy through the PINK1/Parkin pathway]. / 川芎嗪通过PINK1/Parkiné€šè·¯è°ƒæŽ§è‡ªå™¬å¯¹æ–°ç”Ÿå¤§é¼ ç¼ºæ°§ç¼ºè¡€æ€§è„‘ç— çš„å½±å“.

OBJECTIVES: To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism. METHODS: Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62). RESULTS: Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05). CONCLUSIONS: Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.

[Programmed Necrosis Inducers for Cancer Treatment].

Programmed necrosis,a mode of cell death independent of Caspase,is mainly mediated by receptor-interacting protein kinase-1 (RIPK1),receptor-interacting protein kinase-3 (RIPK3),and mixed lineage kinase domain-like protein (MLKL).Studies have demonstrated that programmed necrosis has the dual role of promoting and inhibiting tumor growth and thus we can control the development of tumor by regulating programmed necrosis.The drugs capable of inducing programmed necrosis show potential anti-tumor activity.In addition,inducing programmed necrosis is an effective way to overcome tumor resistance to apoptosis.This paper summarized the mechanisms of programmed necrosis and its relationship with tumors.We focused on the antitumor activity of programmed necrosis inducers including natural products,chemotherapeutic drugs,death receptor ligands,kinase inhibitors,inorganic salts,metal complexes,and metal nanoparticles.These agents will provide new therapeutic candidates for the treatment of tumors,especially the tumors acquiring resistance to apoptosis.

Spectrochemical determination of effects on rat liver of binary exposure to benzo[a]pyrene and 2,2',4,4'-tetrabromodiphenyl ether.

Benzo[a]pyrene (B[a]P) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants. The effects in organisms of exposures to binary mixtures of such contaminants remain obscure. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive analytical technique allowing spectrochemical analysis of macromolecular components, and alterations thereof, within tissue samples. Herein, we employed ATR-FTIR spectroscopy to identify biomolecular changes in rat liver post-exposure to B[a]P and BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) congener mixtures. Our results demonstrate that significant separation occurs between spectra of tissue samples derived from control versus exposure categories (accuracy = 87%; sensitivity = 95%; specificity = 79%). Additionally, there is significant spectral separation between exposed categories (accuracy = 91%; sensitivity = 98%; specificity = 90%). Segregation between control and all exposure categories were primarily associated with wavenumbers ranging from 1600 to 1700 cm-1 . B[a]P and BDE-47 alone, or in combination, induces liver damage in female rats. However, it is suggested that binary exposure apparently attenuates the toxic effects in rat liver of the individual contaminants. This is supported by morphological observations of liver tissue architecture on hematoxylin and eosin (H&E)-stained liver sections. Such observations highlight the difficulties in predicting the endpoint effects in target tissues of exposures to mixtures of environmental contaminants.

Application of Immunohistochemistry and Special Staining Technique in Forensic Traumatic Pathology Identification. / å ç–«ç»„ç»‡åŒ–å­¦åŠç‰¹æ®ŠæŸ“è‰²æŠ€æœ¯åœ¨æ³•åŒ»æŸä¼¤ç— ç†å­¦é‰´å®šä¸­çš„åº”ç”¨.

In forensic traumatic pathology practice, immunohistochemistry and special staining technique play an important role in wound age estimation and complications of traumatic complication identification. They even play an important role in the identification of special cases, such as snakebites and insulin killings. This article reviews the application and value of immunohistochemistry and special staining techniques in forensic traumatic pathology based on the cases of forensic practice reported in literature.

Cytotoxic protein from the mushroom Coprinus comatus possesses a unique mode for glycan binding and specificity.

Glycans possess significant chemical diversity; glycan binding proteins (GBPs) recognize specific glycans to translate their structures to functions in various physiological and pathological processes. Therefore, the discovery and characterization of novel GBPs and characterization of glycan-GBP interactions are significant to provide potential targets for therapeutic intervention of many diseases. Here, we report the biochemical, functional, and structural characterization of a 130-amino-acid protein, Y3, from the mushroom Coprinus comatus Biochemical studies of recombinant Y3 from a yeast expression system demonstrated the protein is a unique GBP. Additionally, we show that Y3 exhibits selective and potent cytotoxicity toward human T-cell leukemia Jurkat cells compared with a panel of cancer cell lines via inducing caspase-dependent apoptosis. Screening of a glycan array demonstrated GalNAcß1-4(Fucα1-3)GlcNAc (LDNF) as a specific Y3-binding ligand. To provide a structural basis for function, the crystal structure was solved to a resolution of 1.2 Å, revealing a single-domain αßα-sandwich motif. Two monomers were dimerized to form a large 10-stranded, antiparallel ß-sheet flanked by α-helices on each side, representing a unique oligomerization mode among GBPs. A large glycan binding pocket extends into the dimeric interface, and docking of LDNF identified key residues for glycan interactions. Disruption of residues predicted to be involved in LDNF/Y3 interactions resulted in the significant loss of binding to Jurkat T-cells and severely impaired their cytotoxicity. Collectively, these results demonstrate Y3 to be a GBP with selective cytotoxicity toward human T-cell leukemia cells and indicate its potential use in cancer diagnosis and treatment.

A Novel Subset of Anti-Inflammatory CD138+ Macrophages Is Deficient in Mice with Experimental Lupus.

Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4+) large peritoneal MΦ. The peritoneal exudate of pristane-treated mice contained mainly Ly6Chi inflammatory monocytes; whereas in MO-treated mice, it consisted predominantly of a novel subset of highly phagocytic MΦ resembling small peritoneal MΦ (SPM) that expressed CD138+ and the scavenger receptor Marco. Treatment with anti-Marco-neutralizing Abs and the class A scavenger receptor antagonist polyinosinic acid inhibited phagocytosis of apoptotic cells by CD138+ MΦ. CD138+ MΦ expressed IL-10R, CD206, and CCR2 but little TNF-α or CX3CR1. They also expressed high levels of activated CREB, a transcription factor implicated in generating alternatively activated MΦ. Similar cells were identified in the spleen and lung of MO-treated mice and also were induced by LPS. We conclude that highly phagocytic, CD138+ SPM-like cells with an anti-inflammatory phenotype may promote the resolution of inflammation in lupus and infectious diseases. These SPM-like cells are not restricted to the peritoneum and may help clear apoptotic cells from tissues such as the lung, helping to prevent chronic inflammation.

Nutrition, Physical Exercise, and the Prevalence of Sarcopenia in Elderly Residents in Nursing Homes in China.

BACKGROUND This study aimed to investigate the factors associated with sarcopenia in elderly residents in three nursing homes in Suzhou City, East China including the association with nutrition and physical exercise. MATERIAL AND METHODS Elderly residents (n=316) from three nursing homes included 112 men and 204 women. The appendicular skeletal muscle index (ASMI), grip strength, and movements were measured to diagnose sarcopenia. The correlation between sarcopenia with age, sex, body mass index (BMI), ASMI, upper arm circumference, calf circumference, muscle content, grip strength, dietary intake, degree and duration of movement were also assessed. RESULTS The prevalence of sarcopenia was 28.8% (30.4% for men and 27.9% for women). Patients with sarcopenia were older compared with controls. Height, BMI, upper arm circumference, calf circumference and arm muscle mass, lower limb muscle mass, limb skeletal muscle index and ASMI, grip strength, and pace of movement were lower than controls. The prevalence of sarcopenia correlated with the intake of meat, fish, eggs, and milk, and duration of weekly aerobic and resistance exercise. Logistic regression analysis showed a positive correlation between the prevalence of sarcopenia and age, and a negative correlation between BMI and consumption of meat, eggs, and milk. CONCLUSIONS The prevalence of sarcopenia in elderly residents in three nursing homes in Suzhou City was 28.8%. Increasing age was a risk factor for sarcopenia. Increased BMI and a diet containing meat, eggs, and milk were protective factors. The findings from this study provide support that adequate dietary protein can prevent sarcopenia in the elderly.

Secondary Metabolites and PI3K Inhibitory Activity of Colletotrichum gloeosporioides, a Fungal Endophyte of Uncaria rhynchophylla.

In the present study, nine compounds (1-9) were isolated from Colletotrichum gloeosporioides (an endophytic fungus from Uncaria rhynchophylla) which was cultured in wheat bran medium. Their structures were elucidated as 4-Epi-14-hydroxy-10, 23-dihydro-24, 25-dehydroaflavinine (1), 10, 23-Dihydro-24,25 -dehydro-21-oxoaflavinine (2), Ergosterol (3), Ergosterol peroxide (4), Mellein (5), 4, 5-dihydroblumenol A (6), Colletotrichine A (7), Cyclo(L-leucyl-L-leucyl) (8), and Brevianamide F (9) based on NMR spectral data, as well as comparing with previous literature data. This is the first report about the isolation of compounds 1-2, 6, and 8-9 from Colletotrichum genus. All compounds were tested for their phosphoinositide 3-kinase (PI3Kα) inhibitory activity. Compounds 8 and 9 showed potent PI3K α inhibitory activity with IC50 values of 38.1 and 4.8 µM, respectively, while the other compounds showed very weak activity at a concentration of 20 µg/mL.

MIST1, an Inductive Signal for Salivary Amylase in Mesenchymal Stem Cells.

Sjögren's syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3). These factors were assessed in the current study for their ability to drive the expression of acinar cell marker, alpha-salivary amylase 1 (AMY1), and ductal cell marker, cytokeratin19 (CK19), in vitro. Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression. In contrast, TCF3 induced neither of those cellular markers. Furthermore, we have identified that mMSCs express muscarinic-type 3 receptor (M3R) mainly in the cytoplasm and aquaporin 5 (AQP5) in the nucleus. While MIST1 did not alter M3R levels in mMSCs, a TCF3 overexpression downregulated M3R expressions in mMSCs. The mechanisms for such differential regulation of glandular markers by these TFs warrant further investigation.

Ultrasonic Remove of Particle Aggregation in Carbon Based Counter Electrodes for Dye-Sensitized Solar Cells.

Low-cost carbon materials (carbon black and graphite power) were applied as substitution of platinum (Pt) in counter electrodes (CEs) for dye-sensitized solar cells (DSSCs). Three fabrication methods, such as ball-milled, pulp-refined, and ultrasonic-crushed, were applied to remove the particle aggregation in the carbon pastes. Then the carbon based pastes were printed on fluorine-doped transparent conducting oxide (FTO) glasses, used as the CEs for DSSCs. Under illumination of 100 mW/cm2, DSSCs with ultrasonic-crushed CEs (U-CEs) show an energy conversion efficiency of 3.57%, which reach to 65.38% of that with conventional sputtered platinum CEs (5.46%). In addition, U-CEs exhibit a higher catalytic activity and a faster charge transfer rate toward the reduction of I-3 to I-.

Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase.

AIM: Atypical angiopoietin-like 8 (ANGPTL8), also known as betatrophin, is known to regulate lipid metabolism. However, its mechanism of action remains elusive. METHODS: HepG2, 3T3-L1, and NIT-1 cells were cultured in amino acid-complete MEM or histidine-free MEM to detect ANGPTL8 expression. The three cell types were treated with or without recombinant ANGPTL8 to investigate its role in lipid metabolism. Hydrodynamic tail vein gene delivery was also used to examine the role of ANGPTL8 in mice. RESULTS: ANGPTL8 is significantly up-regulated in amino acid-deprived cultured cells in vitro. The activation of ANGPTL8 gene transcription was mediated through the RAS/c-RAF/MAPK signaling pathway rather than the general GCN2/ATF4 pathways. ANGPTL8 activated the ERK signal transduction pathway in hepatocytes, adipocytes, and pancreatic ß-cells, up-regulating early growth response transcription factor (Egr1) and down-regulating adipose triglyceride lipase (ATGL). CONCLUSION: ANGPTL8 is a stress-response protein that regulates fat metabolism by suppressing ATGL expression, revealing a mechanistic connection between ANGPTL8 and lipid homeostasis in mammalian cells.

Irisin exerts dual effects on browning and adipogenesis of human white adipocytes.

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes "browning" of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.

"Lupoid hepatitis" in SLE patients and mice with experimental lupus.

The unusual subset of patients with severe hepatitis, hypergammaglobulinemia, arthritis, and LE cells in the blood reported by Henry Kunkel and others suggested to these investigators that "lupoid" hepatitis might share pathogenic mechanisms with SLE. More than half a century later, the etiology of autoimmune hepatitis remains unclear. The occurrence of autoimmune hepatitis in a small fraction (about 3%) of SLE patients in our lupus cohort and in two mouse models of SLE supports their conclusion that lupoid hepatitis may be share pathogenic mechanisms with SLE. The development of autoimmune hepatitis in mice with pristane-induced lupus provides an opportunity to further explore the potential link between these two autoimmune disorders.

[The Spectral Analysis of Laser-Induced Plasma in Laser Welding with Various Protecting Conditions].

The shielding gas plays an important role in the laser welding process and the variation of the protecting conditions has an obvious effect on the welding quality. This paper studied the influence of the change of protecting conditions on the parameters of laser-induced plasma such as electron temperature and electron density during the laser welding process by designing some experiments of reducing the shielding gas flow rate step by step and simulating the adverse conditions possibly occurring in the actual Nd : YAG laser welding process. The laser-induced plasma was detected by a fiber spectrometer to get the spectral data. So the electron temperature of laser-induced plasma was calculated by using the method of relative spectral intensity and the electron density by the Stark Broadening. The results indicated that the variation of protecting conditions had an important effect on the electron temperature and the electron density in the laser welding. When the protecting conditions were changed, the average electron temperature and the average electron density of the laser-induced plasma would change, so did their fluctuation range. When the weld was in a good protecting condition, the electron temperature, the electron density and their fluctuation were all low. Otherwise, the values would be high. These characteristics would have contribution to monitoring the process of laser welding.

The reprogrammed pancreatic progenitor-like intermediate state of hepatic cells is more susceptible to pancreatic beta cell differentiation.

Induced pluripotent stem cells (iPSCs) hold great promise for cell therapy. However, their low efficiency of lineage-specific differentiation and tumorigenesis severely hinder clinical translation. We hypothesized that reprogramming of somatic cells into lineage-specific progenitor cells might allow for large-scale expansion, avoiding the tumorigenesis inherent with iPSCs and simultaneously facilitating lineage-specific differentiation. Here we aimed at reprogramming rat hepatic WB cells, using four Yamanaka factors, into pancreatic progenitor cells (PPCs) or intermediate (IM) cells that have characteristics of PPCs. IM clones were selected based on their specific morphology and alkaline phosphatase activity and stably passaged under defined culture conditions. IM cells did not have iPSC properties, could be stably expanded in large quantity, and expressed all 14 genes that are used to define the PPC developmental stage. Directed differentiation of IM and WB cells by Pdx1-Ngn3-MafA (PNM) into pancreatic beta-like cells revealed that the IM cells are more susceptible to directed beta cell differentiation because of their open chromatin configuration, as demonstrated by expression of key pancreatic beta cell genes, secretion of insulin in response to glucose stimulation, and easy access to exogenous PNM proteins at the rat insulin 1 and Pdx1 promoters. This notion that IM cells are superior to their parental cells is further supported by the epigenetic demonstration of accessibility of Pdx1 and insulin 1 promoters. In conclusion, we have developed a strategy to derive and expand PPC cells from hepatic WB cells using conventional cell reprogramming. This proof-of-principal study may offer a novel, safe and effective way to generate autologous pancreatic beta cells for cell therapy of diabetes.