Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer.

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer have poor outcomes. Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer. Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not yet been reported. AIM: To evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer. METHODS: Thirty-eight patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly divided into two groups: One group received inetetamab combined with the SOX regimen, and the other group received trastuzumab combined with the SOX regimen. After 4-6 cycles, patients with stable disease received maintenance therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were the objective response rate, disease control rate, and adverse events (AEs). RESULTS: Thirty-seven patients completed the trial, with 18 patients in the inetetamab group and 19 patients in the trastuzumab group. In the inetetamab group, the median PFS was 8.5 months, whereas it was 7.3 months in the trastuzumab group (P = 0.046); this difference was significant. The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months (P = 0. 33), and the objective response rate was 50% vs 42% (P = 0.63), respectively; these differences were not significant. Common AEs included leukopenia, thrombocytopenia, nausea, and vomiting. The incidence rates of grade ≥ 3 AEs were 56% in the inetetamab group and 47% in the trastuzumab group (P = 0.63), with no significant difference. CONCLUSION: In the first-line treatment of HER2-positive advanced gastric cancer, inetetamab and trastuzumab showed comparable efficacy. The inetetamab group showed superior PFS, and both groups had good safety.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report.

BACKGROUND: Human epidermal growth factor receptor-2 (HER-2) plays a vital role in tumor cell proliferation and metastasis. However, the prognosis of HER2-positive gastric cancer is poor. Inetetamab, a novel anti-HER2 targeting drug independently developed in China, exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab, which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy. In this case, the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer. CASE SUMMARY: A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension, poor appetite, and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery, followed by tegafur monotherapy for six months. The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma. He received 17 cycles of a combination of inetetamab, an innovative domestically developed anti-HER2 monoclonal antibody, and tegafur chemotherapy as the second-line treatment (inetetamab 200 mg on day 1, every 3 wk combined with tegafur twice daily on days 1-14, every 3 wk). Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months. He tolerated the treatment well without exhibiting any grade 3-4 adverse events. CONCLUSION: Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Nitrogen Deposition Effects on Invasive and Native Plant Competition: Implications for Future Invasions.

Nitrogen (N) deposition has increased dramatically in recent decades, which is significantly affecting the invasion and growth of exotic plants. Whether N deposition leads to invasive alien species becoming competitively superior to native species remains to be investigated. In the present study, an invasive species (Oenothera biennis L.) and three co-occurring native species (Artemisia argyi Lévl. et Vant., Inula japonica Thunb., and Chenopodium album L.) were grown in a monoculture (two seedlings of the same species) or mixed culture (one seedling of O. biennis and one seedling of a native species) under three levels of N deposition (0, 6, and 12 g∙m-2∙year-1). Nitrogen deposition had no effect on soil N and P content. Nitrogen deposition enhanced the crown area, total biomass, leaf chlorophyll content, and leaf N to phosphorus ratio in both invasive and native plants. Oenothera biennis dominated competition with C. album and I. japonica due to its high resource acquisition and absorption capacity (greater height, canopy, leaf chlorophyll a to chlorophyll b ratio, leaf chlorophyll content, leaf N content, leaf mass fraction, and lower root-to-shoot ratio). However, the native species A. argyi exhibited competitive ability similar to O. biennis. Thus, invasive species are not always superior competitors of native species; this depends on the identities of the native species. High N deposition enhanced the competitive dominance of O. biennis over I. japonica by 15.45% but did not alter the competitive dominance of O. biennis over C. album. Furthermore, N deposition did not affect the dominance of O. biennis or A. argyi. Therefore, the species composition of the native community must be considered when preparing to resist future biological invasions. Our study contributes to a better understanding of the invasion mechanisms of alien species under N-loading conditions.

Effects of salt stress on interspecific competition between an invasive alien plant Oenothera biennis and three native species.

Biological invasions and soil salinization have become increasingly severe environmental problems under global change due to sea-level rise and poor soil management. Invasive species can often outcompete native species, but few studies focus on whether invasive alien species are always superior competitors under increasing stressors. We grew an invasive grass species, Oenothera biennis L., and three native grass species (Artemisia argyi Lévl. et Vant., Chenopodium album L., and Inula japonica Thunb.) as a monoculture (two seedlings of each species) or mixture (one seedling of O. biennis and one native species seedling) under three levels of salt treatments (0, 1, and 2 g/kg NaCl) in a greenhouse. We found that invasive O. biennis exhibited greater performance over native C. album and I. japonica, but lower performance compared to A. argyi, regardless of the soil salinity. However, salinity did not significantly affect the relative dominance of O. biennis. Interspecific competition enhanced the growth of O. biennis and inhibited the growth of I. japonica. Although O. biennis seedlings always had growth dominance over C. album seedlings, C. album was not affected by O. biennis at any salt level. At high salt levels, O. biennis inhibited the growth of A. argyi, while A. argyi did not affect the growth of O. biennis. Salt alleviated the competitive effect of O. biennis on I. japonica but did not mitigate the competition between O. biennis and the other two native species. Therefore, our study provides evidence for a better understanding of the invasive mechanisms of alien species under various salinity conditions.

Kir4.1 deletion prevents salt-sensitive hypertension in early streptozotocin-induced diabetic mice via Na + -Cl - cotransporter in the distal convoluted tubule.

OBJECTIVES: Functional impairment of renal sodium handling and blood pressure (BP) homeostasis is an early characteristic manifestation of type 1 diabetes. However, the underlying mechanisms remain unclear. METHODS: Metabolic cages, radio-telemetry, immunoblotting, and electrophysiology were utilized to examine effects of high salt (8% NaCl, HS) intake on Na + /K + balance, BP, Na + -Cl - cotransporter (NCC) function, and basolateral K + channel activity in the distal convoluted tubule (DCT) under diabetic conditions. RESULTS: Improper Na + balance, hypernatremia, and a mild but significant increase in BP were found in streptozotocin (STZ)-induced diabetic mice in response to HS intake for 7 days. Compared to the vehicle, STZ mice showed increased Kir4.1 expression and activity in the DCT, a more negative membrane potential, higher NCC abundance, and enhanced hydrochlorothiazide-induced natriuretic effect. However, HS had no significant effect on basolateral Kir4.1 expression/activity and DCT membrane potential, or NCC activity under diabetic conditions, despite a downregulation in phosphorylated NCC abundance. In contrast, HS significantly downregulated the expression of Na + -H + exchanger 3 (NHE3) and cleaved epithelial sodium channel-γ in STZ mice, despite an increase in NHE3 abundance after STZ treatment. Kir4.1 deletion largely abolished STZ-induced upregulation of NCC expression and prevented BP elevation during HS intake. Interestingly, HS causes severe hypokalemia in STZ-treated kidney-specific Kir4.1 knockout (Ks-Kir4.1 KO) mice and lead to death within a few days, which could be attributed to a higher circulating aldosterone level. CONCLUSIONS: We concluded that Kir4.1 is required for upregulating NCC activity and may be essential for developing salt-sensitive hypertension in early STZ-induced diabetes.

Activation of Kir4.1/Kir5.1 contributes to the cyclosporin A-induced stimulation of the renal NaCl cotransporter and hyperkalemic hypertension.

AIM: Cyclosporin A (CsA) is a widely used immunosuppressive drug that causes hypertension and hyperkalemia. Moreover, CsA-induced stimulation of the thiazide-sensitive NaCl cotransporter (NCC) in the kidney has been shown to be responsible for the development of hyperkalemic hypertension. In this study, we tested whether CsA induces the activation of NCC by stimulating the basolateral Kir4.1/Kir5.1 channel in the distal convoluted tubule (DCT). METHODS: Electrophysiology, immunoblotting, metabolic cages, and radio-telemetry methods were used to examine the effects of CsA on Kir4.1/Kir5.1 activity in the DCT, NCC function, and blood pressure in wild-type (WT) and kidney-specific Kir4.1 knockout (KS-Kir4.1 KO) mice. RESULTS: The single-channel patch clamp experiment demonstrated that CsA stimulated the basolateral 40 pS K+ channel in the DCT. Whole-cell recording showed that short-term CsA administration (2 h) not only increased DCT K+ currents but also shifted the K+ current (IK ) reversal potential to the negative range (hyperpolarization). Furthermore, CsA administration increased phosphorylated NCC (pNCC) levels and inhibited renal Na+ and K+ excretions in WT mice but not in KS-Kir4.1 KO mice, suggesting that Kir4.1 is required to mediate CsA effects on NCC function. Finally, long-term CsA infusion (14 days) increased blood pressure, plasma K+ concentration, and total NCC or pNCC abundance in WT mice, but these effects were blunted in KS-Kir4.1 KO mice. CONCLUSION: We conclude that CsA stimulates basolateral K+ channel activity in the DCT and that Kir4.1 is essential for CsA-induced NCC activation and hyperkalemic hypertension.

Trait value and phenotypic integration contribute to the response of exotic Rhus typhina to heterogeneous nitrogen deposition: A comparison with native Rhus chinensis.

The temporal heterogeneity of nitrogen availability in soils is increasing due to agricultural deposition. We here compared the effects of gradually increasing nitrogen deposition rate and its increasing temporal heterogeneity patterns on the functional traits of seedlings of exotic species Rhus typhina and the native species Rhus chinensis. Nitrogen deposition rates of 0, 8, 20 g N m-2 year-1 and constant, single-peak, and double-peak nitrogen were added to simulate deposition rate and temporal heterogeneity. After 60 days of treatment, R. typhina seedlings had several advantageous growth trait values, such as higher total biomass production, but lower phenotypic plasticity than R. chinensis seedlings. R. typhina seedlings also had higher phenotypic integration, measured as the correlation among functional traits. The increased nitrogen deposition rate affected several traits of the two species differently. Thus, while R. chinensis seedlings allocated more biomass to leaves and less to roots with increasing N deposition, R. typhina seedlings had stable biomass allocation among all N treatments. Chlorophyll content, leaf phosphorus concentration, and water use efficiency increased, but the maximum net photosynthetic rate decreased, with N availability in R. chinensis, but not in R. typhina. Temporal heterogeneity had no significant effect on the total biomass of R. typhina and R. chinensis seedlings. Overall, the performance of R. typhina is better than that of R. chinensis seedlings under different nitrogen deposition treatments, which is due to the significantly advantageous trait values and greater phenotypic integration of R. typhina seedlings, whereas R. chinensis seedlings have higher phenotypic plasticity.

[Impact of Pollutant Emission Reduction on Air Quality During the COVID-19 Pandemic Control in Early 2020 Based on RAMS-CMAQ].

In this work, the relationships between air quality and pollutant emissions were investigated during the COVID-19 pandemic in Shandong Province. During the quarantine period (from January 24 to February 7, 2020), the concentrations of atmospheric pollutants decreased significantly relative to the period before controls were imposed (from January 15 to 23, 2020). Specifically, except for an increase in the concentration of O3, concentrations of PM10, PM2.5, NO2, SO2, and CO decreased for 72.6 µg·m-3 (45.86%), 47.4 µg·m-3(41.24%), 25.6 µg·m-3 (58.00%), 3.0 µg·m-3 (17.71%), and 0.5 mg·m-3 (31.40%), respectively. RAMS-CMAQ simulation showed that meteorological diffusion had an essential role in improving air quality. Influenced by meteorological factors, emissions of PM10, PM2.5, NO2, SO2, and CO were reduced 26.04%, 33.03%, 28.35%, 43.27%, and 23.29%, respectively. Furthermore, the concentrations of PM10, PM2.5, NO2, SO2, and CO were reduced by 19.82%, 8.21%, 29.65%, -25.56%, and 8.12%, respectively, due to pollution emissions reductions during the quarantine period. O3 concentrations increased by 20.51% during quarantine, caused by both meteorological factors (10.47%) and human activities (10.04%). These results indicate that primary pollutants were more sensitive to emissions reductions; however, secondary pollutants demonstrated a lagged response the emissions reduction and were significantly affected by meteorological factors. The linear relationship between ozone and the emissions reduction was not significant, and was inverse overall. Further investigation are now required on the impact of emissions reduction on ozone pollution control.

Antitumor effects of different Ganoderma lucidum spore powder in cell- and zebrafish-based bioassays.

OBJECTIVE: Ganoderma lucidum spore (GLS) is gaining recognition as a medicinal part of G. lucidum and has been reported to possess various pharmacological properties, such as antitumor activity. In this work, wall-broken GLS powder (BGLSP) and wall-removed GLS powder (RGLSP), two kinds of GLS powder with different manufacturing techniques, were compared in terms of contents of active constituents and in vivo and in vitro antitumor effects. METHODS: The ultraviolet and visible spectrophotometry method was used to determine the contents of polysaccharides and total triterpenoids in BGLSP and RGLSP. Seventeen individual triterpenoids were further quantified using ultra-high-performance liquid chromatography and quantitative analysis of multi-components by single marker. The antitumor effects of BGLSP and RGLSP were evaluated using in vitro cell viability assay against human gastric carcinoma SGC-7901, lung carcinoma A549 and lymphoma Ramos and further validated by in vivo zebrafish xenograft models with transplanted SGC-7901, A549 and Ramos. RESULTS: The results showed that the contents of polysaccharides, total triterpenoids and individual triterpenoids of RGLSP were significantly higher than those of BGLSP. Although both BGLSP and RGLSP inhibited the three tumor cell lines in vitro in a dose-dependent manner, the inhibitory effects of RGLSP were much better than those of BGLSP. In the in vivo zebrafish assay, RGLSP exhibited more potent inhibitory activities against tumors transplanted into the zebrafish compared with BGLSP, and the inhibition rates of RGLSP reached approximately 78%, 31% and 83% on SGC-7901, A549 and Ramos, respectively. CONCLUSION: The results indicated that the antitumor effects of GLS were positively correlated with the contents of the polysaccharides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents, and thereby enhance the antitumor activity.

Prophylactic effects of sporoderm-removed Ganoderma lucidum spores in a rat model of streptozotocin-induced sporadic Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum, Lingzhi), also known as "immortality mushroom" has been broadly used to improve health and longevity for thousands of years in Asia. G. lucidum and its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action of G. lucidum spores. AIM OF THE STUDY: The present study investigated the protective effects of sporoderm-deficient Ganoderma lucidum spores (RGLS) against learning and memory impairments and its mechanism of action. MATERIALS AND METHODS: In the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid ß (Aß) expression, Tau expression and phosphorylation, brain-derived neurotrophic factor (BDNF), and the BDNF receptor tropomyosin-related kinase B (TrkB) in the hippocampus were evaluated by Western blot. RESULTS: Treatment with RGLS (360 and 720 mg/kg) significantly enhanced memory in the rat model of STZ-induced sporadic Alzheimer's disease and reversed the STZ-induced increases in Aß expression and Tau protein expression and phosphorylation at Ser199, Ser202, and Ser396. The STZ-induced decreases in neurotrophic factors, including BDNF, TrkB and TrkB phosphorylation at Tyr816, were reversed by treatment with RGLS. CONCLUSION: These findings indicate that RGLS prevented learning and memory impairments in the present rat model of STZ-induced sporadic Alzheimer's disease, and these effects depended on a decrease in Aß expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.

[Characteristics and Sources Apportionment of Fine Particulate Matter in a Typical Coastal City During the Heating Period].

To clarify the pollution characteristics and sources of PM2.5 in Weihai during the heating period, PM2.5 samples from ambient air were collected at three routine air quality monitoring sites from January to March 2018. The OC, EC, water-soluble ions, and elements in PM2.5 were analyzed, and the sources of PM2.5 were identified using the PMF model. The results showed that the average daily mass concentration of PM2.5 was (33.80±22.45) µg·m-3, and the NO3-, NH4+, SO42-, OC, and EC were the main components of PM2.5. As a coastal city, the Cl- ratio was relatively high in PM2.5. Meanwhile, the compositions of PM2.5 were affected by the emission of pollutants with local industrial characteristics. Both NO3-/SO42- and OC/EC showed that mobile sources had a high contribution during the heating period. The acid-base ions in water-soluble ions showed that PM2.5 is weakly alkaline, and NH4+ is excessive. NH4+ mainly existed in the form of NH4NO3 and (NH4)2SO4. During the polluted period, the concentration of secondary pollutants significantly increased, and the mass concentrations of NH4+, NO3-, SO42-, OC, and EC were 4.21, 5.27, 3.23, 2.02, and 1.81 times that of the cleaning period, respectively. The PMF model showed that secondary aerosols were the major source of PM2.5, accounting for 32.4%-36.0% of PM2.5. The contributions of vehicle exhaust, coal combustion, biomass burning, and dust were 15.6%-18.9%, 12.1%-17.8%, 9.0%-10.4%, and 8.6%-11.3%, respectively, while the contributions of process emission (2.1%-8.3%), non-road mobile sources (2.4%-3.7%), and sea salt (3.5%-5.6%) were less.

A study on facial features of children with Williams syndrome in China based on three-dimensional anthropometric measurement technology.

To describe special facial features of children with Williams syndrome in China by using method of three-dimensional craniofacial anthropometry. Using three-dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height-breadth index, nasal breadth-depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3-5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three-dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.

The effect of psychological factors on pain, function and quality of life in patients with rotator cuff tendinopathy: A systematic review.

BACKGROUND: Psychological factors may affect the pain level, shoulder function and quality of life in patients with rotator cuff tendinopathy. OBJECTIVE: To systematically review the prevalence of psychological factors reported in patients with rotator cuff tendinopathy; and to determine the association between psychological factors and pain, function and quality of life in patients with rotator cuff tendinopathy. STUDY DESIGN: Systematic review METHODS: Pubmed, Embase, CINAHL and Web of Science were systematically searched from inception to June 2019. Studies that investigated patients with signs and symptoms suggestive of rotator cuff tendinopathy, and reported psychological variables and patient-reported outcome measures including pain, shoulder function or disability and quality of life. RESULTS: A total of 14 studies were included. Our results showed that 22.8%-26.2% of patients with rotator cuff tendinopathy reported depression; 23% reported anxiety; and 70.2%-89% of patients reported sleep disturbance or insomnia. Overall, nine psychological factors were identified to be associated with pain, function and quality of life in patients with rotator cuff tendinopathy. Low-to-moderate quality of evidence suggests that various psychological factors are associated with pain, function and quality of life in patients with rotator cuff tendinopathy CONCLUSION: This review identified various psychological factors may affect the pain level, shoulder function and quality of life in patients with rotator cuff tendinopathy, and the causal relationship warrants future high-quality prospective studies.

Increased soil moisture aggravated the competitive effects of the invasive tree Rhus typhina on the native tree Cotinus coggygria.

BACKGROUND: Invasive exotic species have caused significant problems, and the effects of extreme precipitation and drought, which might occur more frequently under the global climate change scenarios, on interspecific relationship between invasive and native species remain unclear. RESULTS: We conducted a greenhouse experiment with three soil water levels (30-40%, 50-60%, and 70-80% of field capacity) and two cultivation treatments (monoculture pots, one seedling of either species and mixture pots, one seedling of each species) to investigate soil water content effects on the relationship between invasive Rhus typhina and native Cotinus coggygria. Rhus typhina had lower height but bigger crown area than C. coggygria in the monoculture treatment. Rhus typhina had higher height, bigger crown area and total biomass than C. coggygria in the mixture treatment. Drought decreased the growth parameters, total chlorophyll concentration, and leaf biomass, but did not change gas exchange and other biomass parameters in R. typhina. The growth parameters, leaf area index, biomass parameters, total chlorophyll concentration, and net photosynthetic rate of C. coggygria decreased under drought conditions. The log response ratio (lnRR), calculated as ln (total biomass of a target plant grown in monoculture/total biomass of a target plant grown in mixed culture), of R. typhina was lower than that of C. coggygria. The lnRR of R. typhina and C. coggygria decreased and increased with increase in soil water content, respectively. CONCLUSIONS: Rhus typhina has greater capacity to relatively stable growth to the drought condition than C. coggygria and has strong competition advantages in the mixture with C. coggygria, especially in the drought condition. Our study will help understand the causes of invasiveness and wide distribution of R. typhina under various moisture conditions and predict its expansion under climate change scenarios.

The shift in macrophages polarisation after tendon injury: A systematic review.

BACKGROUND: The role of macrophages (Mφs) in tendon injury healing is controversy. The aims of this study were to determine whether there is a shift in Mφs polarisation after an acute and chronic tendon injury â€‹and to assess whether the Mφs polarisation between the partial and complete rupture is different. METHODS: This systematic review of the scientific literature was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines. PubMed database and Excerpta Medica Database (EMBASE) were used for specific search criteria. Only studies measuring Mφs using specific cell markers in Achilles tendon tissue and rotator cuff tendon tissue were included, respectively. RESULTS: Five Achilles tendon injury studies and four rotator cuff injury studies were included. Expression of the pan Mϕs marker Cluster of Differentiation (CD) 68 was significantly upregulated in acute Achilles tendon ruptures compared to intact tendons, while no significant changes were found in Mφs polarisation markers CD80 (M1 Mφs) and CD206 (M2 Mφs). High levels of CD86 (M1 Mφs) and CD206 were observed in acute partial rupture. Expression of CD68 and CD206 were significantly upregulated in chronic rotator cuff tendinopathy and downregulated as structural failure increases. A low level of CD206 was observed in complete tendon rupture regardless of acute or chronic injury. DISCUSSION AND CONCLUSION: In spite of the limited number of articles included, findings from this study suggested that the process of inflammation plays an important role in acute Achilles tendon injuries, indicated by the increased expression of CD68+ Mφs. Low levels of CD206+ Mφs were constantly observed in complete Achilles tendon rupture, while high levels of CD80+ Mφs and CD206+ Mφs were observed in partial Achilles tendon rupture, which suggested the potential correlation between M2 Mφs and tendon structure. For chronic rotator cuff injury, CD68+ Mφs and CD206+ Mφs were higher in tendinopathic tissues in comparison to the intact control tissues. Both CD68+ Mφs and CD206+ Mφs has an inverse relation to the structural failure in the torn rotator cuff tendon. After tendon rupture, the time point of biopsy specimen collection is an important factor, which could occur in the acute phase or chronic phase. Collectively, the understanding of the roles in Mφs after tendon injury is inadequate, and more research efforts should be devoted to this direction. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This article provided a potential implication on how pan Mφs or M2 Mφs might be associated with ruptured or torn tendon structure. Managing Mφs numbers and phenotypes may lead to possible novel therapeutic approaches to the management of early tendinopathy, early acute tendon rupture, hence, promote healing after restoration surgery.

[Research advances in the relationship between iron deficiency and neurodevelopment in preterm infants].

Iron deficiency (ID) is the most common micronutrient deficiency in children. Due to insufficient iron storage at birth and rapid catch-up growth after birth, preterm infants tend to have a high incidence rate of ID. During the critical period of brain development, ID alters iron-dependent neurometabolism, neurochemistry, neuroanatomy, and gene/protein profiles. This affects the central nervous system and causes the change in neurocognitive and behavioral development. Iron supplementation in infancy cannot reverse neurodevelopmental impairment caused by perinatal ID. The influence of ID on neurodevelopment is time- and region-specific, and in the high-risk population, early diagnosis and optimal iron treatment may help with the recovery of brain function and improve quality of life and long-term prognosis in preterm infants.

Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats.

Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage changes ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure.

[Pollen viability, stigma receptivity and fruiting characteristics of botanical origin of Jinxianlian].

The viability and life span of pollen were evaluated by TTC (2,3,5-triphenyl tetrazlium chloride) and the peroxidase solution, the stigma receptivity were estimated by benzidine-H2O2 method and the fruiting characteristics were investigated. The results showed that (1) Anoectochilus roxburghii and A. formosanus appeared the same up-and-down trend of the pollen viability, increased and then decreased. The storage temperature and storage time had significant impact on the pollen viability. With the extension of storage time, the pollen activity decreased. 4 degrees C refrigerator storage may be extended the pollen vitality. (2) The stigma had receptivity in 1st day and reached the highest level in the 4th day after blooming. A. roxburghii lost receptivity in the 8th day while A. formosanus lost receptivity in the 10th day after blooming. (3) The different pollination had significant impact on seed setting rate. The seed setting rate of artificial cross-pollination was higher than that of the artificial self-pollination. Collecting pollen in the 3rd day and carrying out artificial cross-pollination in the 4th day after blooming can significantly improve seed setting rate. The results provided technical assurance for A. roxburghii and A. formosanus breeding of new varieties and seed breeding.

Data in support of fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice.

This data article contains data related to the research article entitled "Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice" in the Toxicology and Applied Pharmacology [1]. Fumosorinone (FU) is a new inhibitor of protein phosphatase 1B inhibitor, which was isolated from insect pathogenic fungi Isaria fumosorosea. FU was found to inhibit PTP1B activity in our previous study [2]. PTP1B is the physiological antagonist of the insulin signalling pathway. Inhibition of PTP 1B may increase insulin sensitivity [3]. PTP1B has been considered promising as an insulin-sensitive drug target for the prevention and the treatment of insulin-based diseases [4]. We determined the effect of FU on the glucose consumption of IR HepG2 cells. FU caused significant enhancement in glucose consumption by insulin-resistant HepG2 cells compared with control cells.

Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice.

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathways, and its increased activity and expression are implicated in the pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is anticipated to become a potential therapeutic strategy to treat T2DM. Fumosorinone (FU), a new natural product isolated from insect fungi Isaria fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, the effects of FU on insulin resistance and mechanism in vitro and in vivo were investigated. FU increased the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. Furthermore, FU increased the phosphorylation of IRß, IRS-2, Akt, GSK3ß and Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRß, IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties.