Recovery of Ni matte from Ni-bearing electroplating sludge.

In this study, a novel process for the recovery of Ni from Ni-bearing electroplating sludge (ES) is proposed, which involves the carbothermic reduction stage and smelting stage. In the reduction stage, the CaSO4, Fe2O3, and NiO in the ES were reduced by carbon at 1000 °C, and the Ni3S2 and Fe4Ni5S8(Ni-rich phases) were generated. After that, the reduced ES was mixed with SiO2 and smelted at 1500 °C. During the smelting stage, Ni3S2 and Fe4Ni5S8 were melted to form liquid Ni-Fe-S matte and separated from the molten slag by gravity. Finally, 58.5%Ni-13.8%Fe-27.7%S (in weight) matte and vitrified slag were obtained. The recovery ratio of Ni (97.2%) was much higher than that of Fe (14.7%). Besides, the Ni/Fe mass ratio of the ES was 0.7, while the ratio of the prepared matte was about 4.2. Therefore, the selective recovery of Ni was achieved. The obtained Ni matte can be used as the raw material for pure Ni or Ni-bearing chemicals.

Rice NIN-LIKE PROTEIN 3 modulates nitrogen use efficiency and grain yield under nitrate-sufficient conditions.

Nitrogen (N) is an essential macronutrient for crop growth and yield. Improving the N use efficiency (NUE) of crops is important to agriculture. However, the molecular mechanisms underlying NUE regulation remain largely elusive. Here we report that the OsNLP3 (NIN-like protein 3) regulates NUE and grain yield in rice under N sufficient conditions. OsNLP3 transcript level is significantly induced by N starvation and its protein nucleocytosolic shuttling is specifically regulated by nitrate. Loss-of-function of OsNLP3 reduces plant growth, grain yield, and NUE under sufficient nitrate conditions, whereas under low nitrate or different ammonium conditions, osnlp3 mutants show no clear difference from the wild type. Importantly, under sufficient N conditions in the field, OsNLP3 overexpression lines display improved grain yield and NUE compared with the wild type. OsNLP3 orchestrates the expression of multiple N uptake and assimilation genes by directly binding to the nitrate-responsive cis-elements in their promoters. Overall, our study demonstrates that OsNLP3, together with OsNLP1 and OsNLP4, plays overlapping and differential roles in N acquisition and NUE, and modulates NUE and the grain yield increase promoted by N fertilizer. Therefore, OsNLP3 is a promising candidate gene for the genetic improvement of grain yield and NUE in rice.

Effect of surgical starting time and season on prognosis in octogenarians with colorectal cancer: a retrospective study.

Aim: To investigate the effect of surgical starting time and season on the prognosis of octogenarians with colorectal cancer. Patients & methods: A total of 291 patients aged 80 years or above who received elective colectomy for colorectal cancer between January 2007 and December 2018 in the National Cancer Center in China were included. Results: No significant time- or season-dependent difference in overall survival for all clinical stages was found in the study. Comparing perioperative outcomes, the morning group had a longer operative time than the afternoon group (p = 0.03), but no significant difference was found based on the season of colectomy. Conclusion: These findings provide insights into clinical outcomes for colorectal cancer patients aged more than 80 years.

Recurrent studies have demonstrated that in heart surgery, different surgical starting times can affect the patients' outcomes, mainly due to the 24-h cyclic variations in heart function. This variability also exists in bowel function. The surgical outcomes of elderly patients aged over 80 years are more susceptible to external factors due to their frailty, so we wanted to compare the differences in prognosis of elderly patients who underwent surgery at different times and seasons.

A comprehensive study of celastrol metabolism in vivo and in vitro using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry.

Celastrol has attracted great attention owing to its anti-arthritis, antioxidant, and anticancer activities. Nevertheless, its metabolism in vivo (rats) and in vitro (rat liver microsomes and intestinal flora) has not been comprehensively characterized. In this study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry was used as a rapid and sensitive approach for studying the metabolism of celastrol in vivo and in vitro. A total of 43 metabolites were identified and characterized. These include 26 metabolites in vivo, and 28 metabolites in vitro (nine metabolites in rat liver microsomes and 24 metabolites in rat intestinal flora). Additionally, the celastrol-biotransformation capacity of the intestinal tract was confirmed to exceed that of the liver. Furthermore, the metabolic profile of celastrol is summarised. The information obtained from this study may provide a basis for understanding the pharmacological mechanisms of celastrol and will be beneficial for clinical applications.

Microvascular invasion risk scores affect the estimation of early recurrence after resection in patients with hepatocellular carcinoma: a retrospective study.

BACKGROUND: Microvascular invasion (MVI) is a histological factor that is closely related to the early recurrence of hepatocellular carcinoma (HCC) after resection. To investigate whether a noninvasive risk score system based on MVI status can be established to estimate early recurrence of HCC after resection. METHODS: Between January 2018 to March 2021, a total of 108 patients with surgically treated single HCC was retrospectively included in our study. Fifty-one patients were pathologically confirmed with MVI and 57 patients were absent of MVI. Univariate and multivariate logistic regression analysis of preoperative laboratory and magnetic resonance imaging (MRI) features were used to screen noninvasive risk factors in association with MVI in HCC. Risk scores based on the odds ratio (OR) values of MVI-related risk factors were calculated to estimate the early recurrence after resection of HCC. RESULTS: In multivariate logistic regression analysis, tumor size > 2 cm (P = 0.024, OR 3.05, 95% CI 1.19-11.13), Prothrombin induced by vitamin K absence-II > 32 mAU/ml (P = 0.001, OR 4.13, 95% CI 1.23-11.38), irregular tumor margin (P = 0.018, OR 3.10, 95% CI 1.16-8.31) and apparent diffusion coefficient value < 1007 × 10- 3mm2/s (P = 0.035, OR 2.27, 95% CI 1.14-7.71) were independent risk factors correlated to MVI in HCC. Risk scores of patients were calculated and were then categorized into high or low-risk levels. In multivariate cox survival analysis, only high-risk score of MVI was the independent risk factor of early recurrence (P = 0.009, OR 2.11, 95% CI 1.20-3.69), with a sensitivity and specificity of 0.52, 0.88, respectively. CONCLUSION: A risk score system based on MVI status can help stratify patients in high-risk of early recurrence after resection of HCC.

Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain.

BACKGROUND: Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain. METHODS: Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord. RESULTS: The analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord. CONCLUSIONS: The combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.

Controllable synthesis of Mo2C with different morphology and application to electrocatalytic hydrogen evolution reaction.

In order to evaluate the effect of precursors and synthesis strategies on catalytic ability of Mo2C in the hydrogen evolution reaction (HER), four kinds of Mo2C were synthesized using two kinds of MoO3by two strategies. Compared with the one-step direct carbonization strategy, Mo2C with a large special surface area and a better performance could be synthesized by the two-step strategy composed of a nitridation reaction and a carbonization reaction. Additionally, the as-prepared porous Mo2C nanobelts (NBs) exhibit good electrocatalytic performance with a small overpotential of 165 mV (0.5 M H2SO4) and 124 mV (1 M KOH) at 10 mA cm-2, as well as a Tafel slope of 58 mV dec-1(0.5 M H2SO4) and 59 mV dec-1(1 M KOH). The excellent catalytic activity is ascribed to the nano crystallites and porous structure. What's more, the belt structure also facilitates the charge transport in the materials during the electrocatalytic HER process. Therefore, the two-step strategy provides a new insight into the structural design with superior performance for electrocatalytic HER.

[Effects and pathophysiological significance of intestinal flora on the enteric neuro-endocrine-immune system].

Interactions among the nervous, the endocrine and the immune systems enable the gut to respond to the dietary products, pathogens and microbiota, which maintains the homeostasis of the body. However, dysbiosis may induce or aggravate the gastrointestinal (GI) and extra-GI diseases through changing the activities of enteric nervous system (ENS), enteroendocrine cells and enteric immune cells. Here we review recent advances in the understandings on how intestinal flora may impact the enteric neuro-endocrine-immune system in the gut, thereby contributing to the regulation of pathophysiological processes.

Genetic polymorphisms, forensic efficiency, and phylogenetic analysis of 15 autosomal STR loci in the Uygur population of Ili Kazakh Autonomous Prefecture, Northwestern China.

The genetic polymorphisms of 15 autosomal short tandem repeat (STR) loci were analyzed in 449 individuals of the Uygur population from Ili Kazakh Autonomous Prefecture, Northwestern China. Phylogenetic analysis was performed among the Ili Uygur population and other relevant populations. The neighbor-joining tree and multidimensional scaling plot were generated based on the Nei's standard genetic distance. We found a total of 173 alleles with corresponding frequencies ranging from 0.5022 to 0.0011. The combined powers of discrimination and exclusion for the 15 autosomal STR loci were 0.99999999985 and 0.99999880065, respectively. Population comparisons indicated that the Ili Uygur population had a relatively close genetic relationship with the Uygur populations from other regions of China. The pairwise genetic distance and P-values between Ili Uygur and 10 published populations showed that no statistically significant differences existed between the Ili Uygur population and the Kashi, Kashgar, and Kotan Uygur. Therefore, the Ili Uygur population has its own unique Uygur genetic characteristics that were different from the other ethnic populations of China.

Simple and fast approach to exploit the spectral reflection properties of liquid media.

Bidirectional reflectance distribution functions (BRDFs) are of importance for their wide applications. In this study, we presented a simple and fast approach to measure the spectral BRDF of both solid and liquid samples. Based on this approach, we fabricated a prototype and measured the BRDF value of some liquid samples such as water and NaCl solution at different wavelengths. According to the experimental data, we discussed the trend of the BRDF value of the NaCl solution of different concentrations. Then, the experimental data of the different NaCl solution at 637 nm were used to invert the parameters of a five-parameter model. Additionally, we fitted the parameters as a polynomial.

Effects of propofol/remifentanil-based total intravenous anesthesia versus sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-ß and prognosis after breast cancer surgery: a prospective, randomized and controlled study.

BACKGROUND: Vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß) have been involved in tumor growth and metastasis. Sevoflurane may promote angiogenesis, whereas propofol can present an anti-angiogenic effect. In this study, we compared the effects of propofol/remifentanil-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-ß, as well as recurrence- free survival (RFS) rates in the patients undergoing breast cancer surgery. METHODS: Eighty female patients undergoing breast cancer resection were enrolled and randomized to receive either sevoflurane-based inhalational anesthesia (SEV group) or propofol/remifentanil-based TIVA (TIVA group). The serum concentrations of VEGF-C and TGF-ß before and 24 h after surgery were measured and RFS rates over a two-year follow-up were analyzed in both groups. The postoperative pain scores assessed using a visual analogue scale (VAS) and the use of perioperative opioids were also evaluated. RESULTS: Although VAS scores at 2 h and 24 h after surgery were comparable between the two groups, there were more patients receiving postoperative fentanyl in the TIVA group (16[40%]) compared with the SEV group (6[15%], p = 0.023). VEGF-C serum concentrations increased after surgery from 105 (87-193) pg/ml to174 (111-281) pg/ml in the SEV group (P = 0.009), but remained almost unchanged in the TIVA group with 134 (80-205) pg/ml vs.140(92-250) pg/ml(P = 0.402). The preoperative to postoperative change for VEGF-C of the SEV group (50 pg/ml) was significantly higher than that of the TIVA group (12 pg/ml) with a difference of 46 (- 11-113) pg/ml (P = 0.008). There were also no significant differences in the preoperative and postoperative TGF-ß concentrations between the two groups. The two-year RFS rates were 78% and 95% in the SEV and TIVA groups (P = 0.221), respectively. CONCLUSION: In comparison with sevoflurane-based inhalational anesthesia, propofol/remifentanil -based total intravenous anesthesia can effectively inhibit the release of VEGF-C induced by breast surgery, but didn't seem to be beneficial in the short-term recurrence rate of breast cancer. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800017910 . Retrospectively Registered (Date of registration: August 20, 2018).

Effects of sevoflurane and propofol on the development of pneumonia after esophagectomy: a retrospective cohort study.

BACKGROUND: Postoperative pneumonia (PP) is one of the common complications following esophagectomy and associated with poor short- and long-term outcomes. Sevoflurane and propofol, which have inflammatory-modulating effects, are common used general anesthetics. This study aimed to compare the effects of anesthesia with sevoflurane and propofol on the development of PP after esophageal surgery for cancer. METHODS: The electronic medical records of patients who underwent elective esophagectomy between July 2013 and July 2016 were reviewed. We conducted univariate and multivariate logistics analysis and propensity score matching analysis to compare the effect of sevoflurane and propofol on the incidence of PP and to identify the risk factors for PP after esophagectomy. RESULTS: Overall, the incidence of postoperative pneumonia was 9.5%. There was no significant difference in the rates of PP between sevoflurane group and propofol group either before or after propensity score matching (9.6% vs 8.0%, P = 0.606; 7.7% vs 6.4%, P = 0.754, respectively). Univariate and multivariate analysis revealed that alcohol use (OR 1.513; 95% CI 1.062-2.156), surgical procedure (Sweet: referent; Ivor-Lewis: OR 1.993; 95% CI 1.190-3.337; Three-incision: OR 1.878; 95% CI 1.296-2.722) and surgeon experience (high-volume: referent; low-volume: OR 1.525; 95% CI 1.090-2.135) were significant risk factors of postoperative pneumonia. CONCLUSIONS: Sevoflurane did not differ from propofol in terms of affecting the risk of PP development after esophagectomy.

Stress-related arterial hypertension in Gper-deficient rats.

Numerous studies have demonstrated that estrogens may exert multifaceted effects on the cardiovascular system via activating the classical nuclear receptors ERα or ERß and the novel G protein coupled estrogen receptor (Gper). However, some studies have reported inconsistent cardiovascular phenotypes in Gper-deficient mice. The current study was aimed to reveal the effects of genetic deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats. Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9 gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6 males) were measured under awake and restrained conditions through the non-invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5 to 9, indicative of stress-related sympathoexcitation in the first few days and gradual adaptation to the restrained stress in later days. Gper-deficient rats had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to day 3) and similar ABP in later days of measurement compared with the WT rats. The heart rate of male Gper-deficient rats was consistently higher than that of the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats appeared to show slower body weight gain than the WT counterparts during the study period. Under anesthesia, ABP of Gper-deficient rats was not significantly different from their WT counterparts. These results indicate that Gper-deficient rats may be more sensitive to stress-induced sympathoexcitation and highlight the importance of Gper in the regulation of the cardiovascular function in stressful conditions.

Comparison of the adipogenesis in intramuscular and subcutaneous adipocytes from Bamei and Landrace pigs.

Fat deposition is a complex process involving proliferation, differentiation, and lipogenesis of adipocytes. Bamei and Landrace are considered to represent fat- and lean-type pig breeds. Subcutaneous (SC) and intramuscular (IM) pre-adipocytes were cultured to compare the proliferation and lipogenesis in these breeds. The differentiated adipocytes were exposed to glucose or insulin to evaluate their effects on lipogenesis and lipogenic gene expression. Pre-adipocytes proliferated dramatically faster in SC vs. IM cells, and in Bamei vs. Landrace breeds. Lipogenesis and lipogenic gene expression had a greater increase in Bamei than in Landrace, and in SC vs. IM in the process of differentiation. Glucose markedly promoted lipogenesis and lipogenic gene expression in differentiated adipocytes. The stimulation of high-glucose levels on lipogenesis and ChREBP and lipogenic gene expression was higher in SC than IM adipocytes, and in Bamei vs. Landrace. Insulin largely increased SREBP-1c expression, however it modestly stimulated lipogenesis and lipogenic gene expression, and there was no difference between cell populationsor between breeds. These data demonstrated that regional and varietal differences obviously existed in the development of porcine adipocytes. The proliferation and differentiation capacity of pre-adipocytes, and the adipocyte lipogenesis stimulated by glucose, are stronger in Bamei than Landrace, and in SC vs. IM adipocytes independent of breed.

Pancreatic ectopic thyroid tissue: A case report and analysis of literature.

Ectopic thyroid is a rare malformation induced by a migration defect in the developing gland during embryogenesis. In 90% of cases, the ectopic thyroid is located in the lingual region, whereas it is extremely rare in the abdominal cavity, particularly in the pancreas. A 50-year-old female patient presented to the Taizhou First People's Hospital with a complaint of recurrent mid-lower abdominal pain and diarrhea for approximately a month. The abdominal computed tomography scan revealed a space-occupying lesion with abundant blood supply in the head of the pancreas during the consultation. This led to the suspicion of a neuroendocrine tumor. The doctor considered that this lesion in the head of the pancreas could be responsible for the patient's incontinence. A laparoscopic pancreaticoduodenectomy was performed after relevant tests were undertaken and contraindications were ruled out. The patient was diagnosed with ectopic thyroid of the pancreas through postoperative pathology. Ectopic thyroid can be considered in middle-aged and elderly women who present with a mass with abundant blood supply and an unknown diagnosis. Subsequent treatments should be decided after fine-needle aspiration cytology.

Why are S(n)N4 (n = 1-4) species "missing"? Answers in a broader theoretical context of binary S-N compounds.

Computational investigations of the thermochemical stability and kinetic persistence of binary S(x)N(y) compounds, SN(2), S(2)N(2), S(3)N(2), S(4)N(2), SN(4), S(2)N(4), S(3)N(4), and S(4)N(4), explain why some S(x)N(y) stoichiometries exist but not others. There is no direct link between the Hückel 4n + 2 π-electron count rule and the computed heats of formation (per atom) of the lowest-energy neutral S(n)N(4) (n = 1-4) isomers, but kinetic persistence often is paramount. Thus, the five lowest-energy S(2)N(4) minima at the B3LYP/6-311+G(3df) density functional theory level (A1-A5) all not only have high computed heats of formation [Δ(f)H°(0 K) > 131 kcal/mol or >22 kcal/mol/atom] but also have low dissociation barriers (less than 21.5 kcal/mol for the most favorable pathways). For comparison, the persistent (but potentially explosive!) cyclic S(2)N(2)-c has about the same high heat of formation (per atom) as the least unfavorable S(2)N(4) isomer, but its barrier to ring opening (51 kcal/mol) is much higher. Although aromatic, both SN(4) (6π electron) and S(3)N(4) (10π electron) have low dissociation barriers and, like S(2)N(4), are also absent from the S-N binary family.

[Relationship between oxidative stress and depression in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the relationship between oxidative stress and depression in patients with rheumatoid arthritis (RA). METHODS: In the study, 129 patients with RA were assessed using the Hamilton depression rating scale (HAMD), Zung self-rating depression scale (SDS), Zung self-rating anxiety scale (SAS), symptom checklist 90 (SCL-90), and other multiple item questionnaires. Oxidative-stress-related parameters in sera and indexes of oxidative damage were monitored during a pretreatment period. The patients were divided into depression (group A, HAMD≥20) and nondepression groups (group B,HAMD<20) based on an HAMD score cutoff of 20. In addition, 20 healthy donors were classified as group C. RESULTS: A statistically significant increase in SDS score was observed in group A (59.12±10.18) when compared with group B (39.24±5.02) (t=0.42,P < 0.01). A statistically significant increase was observed in SAS score in group A (59.12±10.18) in comparison with group B (39.24±5.02) (t=1.48,P<0.01). Antisuperoxide anion capacity was significantly decreased in group A (393.76±43.35) in comparison with group B (456.98±93.86) and group C (483.51±30.64) (F=3.95, P=0.03), whereas serum malondialdehyde (MDA) levels of group A (13.84±3.35) were higher than those of group B (9.42±3.52) and group C (7.86±3.21)(F=12.01, P=0.01). Pearson correlation analysis revealed that depression was positively correlated with MDA (r=0.58,P<0.05), but negatively with A-ASC (r =-0.30, P<0.05). CONCLUSION: The oxidative damage occurs in patients with rheumatoid arthritis, and lower antioxidant defences exist in depressive patients. The oxidative stress may promote the development of depression.

Role of Keap1-Nrf2/ARE signal transduction pathway in protection of dexmedetomidine preconditioning against myocardial ischemia/reperfusion injury.

OBJECTIVE: To explore the role and mechanism of the Kelch sample related protein-1-nuclear factor erythroid-2 related factor 2/antioxidant response element (Keap1-Nrf2/ARE) signaling pathway in protection of dexmedetomidine (DEX) preconditioning against myocardial ischemia/reperfusion injury (MIRI). METHODS: A total of 70 male SD rats were randomly divided into seven equal groups (n=10): blank control (S group), ischemia/reperfusion injury (C group), DEX preconditioning (DEX group), tertiary butylhydroquinone (tBHQ) control (tBHQ group), combined tBHQ and DEX preconditioning (tBHQ+DEX group), all-trans retinoic acid (ATRA) control (ATRA group), and combined ATRA and DEX preconditioning (ATRA+DEX group). Serum creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) concentrations were measured by ELISA kits, and the infarct size (IS) was assessed by Evan's blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Oxidative stress was assessed through Western blotting for expression of Keap1-Nrf2/ARE pathway members and oxidative stress markers. RESULTS: Cardioprotection of DEX, tBHQ, and tBHQ+DEX preconditioning treatments were shown as lower concentrations of serum CK-MB and cTnI and a smaller IS following MIRI in rats compared with those of MIRI rats without pre-treatment. In addition, tBHQ+DEX preconditioning exhibited stronger myocardial protection compared with DEX preconditioning. Mechanistically, the cardioprotection offered by DEX, tBHQ, and tBHQ+DEX preconditioning treatments was mediated via exerting antioxidant stress through activation of the Keap1-Nrf2/ARE signal transduction pathway. Conversely, the protective effects of DEX were diminished by blocking the Keap1-Nrf2/ARE pathway with inhibitor ATRA. CONCLUSION: DEX preconditioning protects against MIRI by exerting antioxidant stress through activation of the Keap1-Nrf2/ARE signal transduction pathway, while inhibition of the Keap1-Nrf2/ARE signal transduction pathway reverses the protective effect of DEX preconditioning on MIRI.

Patient-Derived Pancreatic Cancer Cells Induce C2C12 Myotube Atrophy by Releasing Hsp70 and Hsp90.

Pancreatic cancer (PC) patients are highly prone to cachexia, a lethal wasting syndrome featuring muscle wasting with an undefined etiology. Recent data indicate that certain murine cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 through extracellular vesicles (EVs) to activate p38ß MAPK-mediated catabolic pathways primarily through Toll-like receptor 4 (TLR4). However, whether human PC induces cachexia through releasing Hsp70 and Hsp90 is undetermined. Here, we investigated whether patient-derived PC cells induce muscle cell atrophy directly through this mechanism. We compared cancer cells isolated from patient-derived xenografts (PDX) from three PC patients who had cachexia (PCC) with those of three early-stage lung cancer patients without cachexia (LCC) and two renal cancer patients who were not prone to cachexia (RCC). We observed small increases of Hsp70 and Hsp90 released by LCC and RCC in comparison to non-cancer control cells (NCC). However, PCC released markedly higher levels of Hsp70 and Hsp90 (~ 6-fold on average) than LCC and RCC. In addition, PCC released similarly increased levels of Hsp70/90-containing EVs. In contrast to RCC and LCC, PCC-conditioned media induced a potent catabolic response in C2C12 myotubes including the activation of p38 MAPK and transcription factor C/EBPß, upregulation of E3 ligases UBR2 and MAFbx, and increase of autophagy marker LC3-II, resulting in the loss of the myosin heavy chain (MHC ~50%) and myotube diameter (~60%). Importantly, the catabolic response was attenuated by Hsp70- and Hsp90-neutralizing antibodies in a dose-dependent manner. These data suggest that human PC cells release high levels of Hsp70 and Hsp90 that induce muscle atrophy through a direct action on muscle cells.

Exploring the Efficacy of Biocontrol Microbes against the Fungal Pathogen Botryosphaeria dothidea JNHT01 Isolated from Fresh Walnut Fruit.

Biological control by antagonistic microorganisms are an effective and environmentally friendly approach in postharvest disease management. In order to develop a biocontrol agent for fresh walnut fruit preservation, the potential biocontrol effects of Bacillus amyloliquefaciens RD.006 and Hanseniaspora uvarum FA.006 against the main fungal pathogen of walnuts were evaluated. Botryosphaeria species showed the highest detection, and the JNHT01 strain showed the strongest pathogenicity. Bot. dothidea JNHT01 caused gray mold and brown rot on fresh walnuts, and its incidence rate reached 100% after an 8 days incubation. The growth of this fungal strain can be promoted by lighting, with a maximum growth rate achieved at a pH of 7 and at 28 °C. B. amyloliquefaciens RD.006 and H. uvarum FA.006 supernatants at a concentration of 1-15% v/v showed antifungal activity. The mycelial growth inhibition rates of Bot. dothidea JNHT01 were 23.67-82.61% for B. amyloliquefaciens RD.006 and 1.45-21.74% for H. uvarum FA.006. During Bot. dothidea JNHT01 growth, the biomass, nucleic acid leakage, and malondialdehyde content gradually increased, while the DPPH scavenging capacity and SOD activity decreased. The B. amyloliquefaciens RD.006 and H. uvarum FA.006 strains showed antifungal activity by damaging fungal cell membranes and reducing fungal antioxidant activity. Moreover, the antifungal effect of B. amyloliquefaciens RD.006 was higher than that of H. uvarum FA.006. Hence, the RD.006 strain of B. amyloliquefaciens can be considered a potential biocontrol agent for the management of postharvest walnut diseases caused by Bot. dothidea.