Curcumin in the treatment of inflammation and oxidative stress responses in traumatic brain injury: a systematic review and meta-analysis.

Background and aim: Traumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root of Curcuma longa, has demonstrated neuroprotective properties both in vitro and in vivo. Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. This paper conducts a systematic review and meta-analysis to explore curcumin's role in TBI animal models extensively. The findings offer valuable insights for future human clinical trials evaluating curcumin as a therapeutic supplement or nutraceutical in TBI management. Methods: Comprehensive literature searches were conducted across MEDLINE, Embase, Cochrane, Web of Science, and Google Scholar databases. These searches aimed to identify relevant manuscripts in all languages, utilizing the keywords "curcumin" and "traumatic brain injury." Results: The final quantitative analysis included 18 eligible articles corresponding to animal studies. The analysis revealed that curcumin significantly reduced inflammatory cytokines, including IL-1ß (p = 0.000), IL-6 (p = 0.002), and TNF-α (p = 0.000), across various concentrations, time points, and administration routes. Additionally, curcumin markedly enhanced the activity of oxidative stress markers such as SOD (p = 0.000), Sir2 (p = 0.000), GPx (p = 0.000), and Nrf2 (p = 0.000), while reducing MDA (p = 0.000), 4-HNE (p = 0.001), and oxyprotein levels (p = 0.024). Furthermore, curcumin improved cerebral edema (p = 0.000) and upregulated neuroprotective factors like synapsin I (p = 0.019), BDNF (p = 0.000), and CREB (p = 0.000), without reducing mNSS (p = 0.144). About autophagy and apoptosis, curcumin increased the activity of Beclin-1 (p = 0.000) and Bcl-2 (p = 0.000), while decreasing caspase-3 (p = 0.000), the apoptosis index (p = 0.000), and P62 (p = 0.002). Conclusion: Curcumin supplementation positively affects traumatic brain injury (TBI) by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human TBI. However, this conclusion necessitates further substantiation through high-quality literature and additional randomized controlled trials (RCTs). Systematic Review Registration: https://www.crd.york.ac.uk/prospero/. The registration number of PROSPERO: CRD42023452685.

Recent advances in the bovine ß-casein gene mutants on functional characteristics and nutritional health of dairy products: Status, challenges, and prospects.

ß-casein is the second most abundant form of casein in milk. Changes in amino acid sequence at specific positions in the primary structure of ß-casein in milk will produce gene mutations that affect the physicochemical properties of dairy products and the hydrolysis site of digestive enzymes. The screening method of ß-casein allele frequency detection in dairy products also has attracted the extensive attention of scientists and farmers. The A1 and A2 ß-casein is the two usual mutation types, distinguished by histidine and proline at position 67 in the peptide chain. This paper summarizes the effects of A1 and A2 ß-casein on the physicochemical properties of dairy products and evaluates the effects on human health, and the genotyping methods were also concluded. Impressively, this review presents possible future opportunities and challenges for the promising field of A2 ß-casein, providing a valuable reference for the development of the functional dairy market.

Breast cancer metastases to the thyroid and stomach: A case report.

The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.

The anti-tumor efficiency of low-dose apatinib-based chemotherapy in pretreated HER2-negative breast cancer with brain metastases.

BACKGROUND: More than half of the metastatic breast cancer patients with brain metastases (BCBM) are HER-2 negative, and the prognosis of HER2-negative BCBM is dismal. But few clinical trials have investigated systemic therapies for this subgroup of patients. METHODS: This real-world study included 58 HER2-negative BCBMs who received low-dose apatinib (250 mg daily) in combination with chemotherapy between 18 March 2017 and 31 December 2021. The objective response rate (ORR) of the central nervous system, clinical benefit rate (CBR), progression-free survival of central nervous system (CNS-PFS) and overall survival (OS) were analyzed. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for CNS-PFS and OS. RESULTS: At the cut-off date, the median follow-up time was 28.2 months. Of the 58 patients, 36 patients were HR+/HER2-, and 22 patients were TNBC. The CNS-ORR was 17.2% (95%CI 9.6% to 28.9%) and the CBR was 53.4% (95%CI 40.8% to 65.7%). The median duration of CNS-PFS for the entire cohort was 6.4 months, and the median OS was 10.7 months. The median CNS-PFS and OS were not affected by hormone receptor status, disease-free survival, the number of prior lines of therapy and local treatment. The most common grade 2-3 adverse events associated with low-dose apatinib were hypertension (20.6%), elevated bilirubin (10.4%), hypothyroidism (10.3%), and hand-foot skin reaction (10.3%). CONCLUSION: Apatinib-based chemotherapy demonstrates potential feasibility with acceptable tolerance for HER2-negative BCBM. Its clinical application in BCBM still needs further verification.

HER2-negative breast cancer patients with brain metastases (BCBM) face an extremely poor prognosis, and a lack of effective treatment options. Apatinib, as a small molecule anti-angiogenic TKI, might have special central nervous system activity. Apatinib-based chemotherapy exhibits good tolerance and gains a favorable survival for HER2-negative BCBM.

A single-arm phase II clinical trial of anlotinib combined with chemotherapy for the treatment of metastatic triple-negative breast cancer.

Background: Anlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC). Methods: This phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety. Results: During May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1-25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs. Conclusion: In this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable.

The miR156b-GmSPL2b module mediates male fertility regulation of cytoplasmic male sterility-based restorer line under high-temperature stress in soybean.

High-temperature (HT) stress at flowering stage causes significant damage to soybean, including pollen abortion and fertilization failure, but few genes involved in male fertility regulation under HT stress in soybean have been characterized. Here, we demonstrated that miR156b-GmSPL2b module involved in male fertility regulation of soybean cytoplasmic male sterility (CMS)-based restorer line under HT stress. Overexpression of miR156b decreased male fertility in soybean CMS-based restorer line and its hybrid F1 with CMS line under HT stress. RNA-seq analysis found that miR156b mediated male fertility regulation in soybean under HT stress by regulating the expression of pollen development and HT response related genes. Metabolomic analysis of miR156bOE revealed reduction in flavonoid content under HT stress. Integrated transcriptomic and metabolomic analysis showed that the overexpression of miR156b caused flavonoid metabolism disorder in soybean flower bud under HT stress. Knockout of GmSPL2b also decreased the thermotolerance of soybean CMS-based restorer line during flowering. Moreover, GmSPL2b turned out to be directly bounded to the promoter of GmHSFA6b. Further verification indicated that GmHSFA6b overexpression enhanced HT tolerance in Arabidopsis during flowering. Substance content and gene expression analysis revealed that miR156b-GmSPL2b may mediate reactive oxygen species clearance by regulating flavonoid metabolism, thus participating in the regulation of male fertility in soybean under HT stress. This study not only provided important progress for understanding the molecular mechanism of miR156b-GmSPL2b regulating the male fertility of soybean CMS-based restorer line under HT stress, but also provided genetic resources and theoretical basis for creating HT-tolerant strong restorer lines.

[Effect of acupuncture on functional delayed gastric emptying after gastric cancer surgery based on enhance recovery after surgery].

OBJECTIVE: To observe the clinical effect of acupuncture for functional delayed gastric emptying after gastric cancer surgery on the basis of routine treatment. METHODS: A total of 80 patients with functional delayed gastric emptying after gastric cancer surgery were randomly divided into an observation group (40 cases, 3 cases dropped off) and a control group (40 cases, 1 case dropped off). The control group was treated with routine treatment, e.g. continuous gastrointestinal decompression. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Gongsun (SP 4), Sanyinjiao (SP 6), 30 min each time, once a day, 5 days as a course, 1-3 courses were required. The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay were compared in the two groups, and the clinical effect was evaluated. RESULTS: The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay in the observation group were shorter than the control group (P<0.001). CONCLUSION: On the basis of routine treatment, acupuncture could accelerate the recovery of patients with functional delayed gastric emptying after gastric cancer surgery.

Retrieval of Leaf Chlorophyll Contents (LCCs) in Litchi Based on Fractional Order Derivatives and VCPA-GA-ML Algorithms.

The accurate estimation of leaf chlorophyll content (LCC) is a significant foundation in assessing litchi photosynthetic activity and possible nutrient status. Hyperspectral remote sensing data have been widely used in agricultural quantitative monitoring research for the non-destructive assessment of LCC. Variable selection approaches are crucial for analyzing high-dimensional datasets due to the high danger of overfitting, time-intensiveness, or substantial computational requirements. In this study, the performance of five machine learning regression algorithms (MLRAs) was investigated based on the hyperspectral fractional order derivative (FOD) reflection of 298 leaves together with the variable combination population analysis (VCPA)-genetic algorithm (GA) hybrid strategy in estimating the LCC of Litchi. The results showed that the correlation coefficient (r) between the 0.8-order derivative spectrum and LCC had the highest correlation coefficients (r = 0.9179, p < 0.01). The VCPA-GA hybrid strategy fully utilizes VCPA and GA while compensating for their limitations based on a large number of variables. Moreover, the model was developed using the selected 14 sensitive bands from 0.8-order hyperspectral reflectance data with the lowest root mean square error in prediction (RMSEP = 5.04 µg·cm-2). Compared with the five MLRAs, validation results confirmed that the ridge regression (RR) algorithm derived from the 0.2 order was the most effective for estimating the LCC with the coefficient of determination (R2 = 0.88), mean absolute error (MAE = 3.40 µg·cm-2), root mean square error (RMSE = 4.23 µg·cm-2), and ratio of performance to inter-quartile distance (RPIQ = 3.59). This study indicates that a hybrid variable selection strategy (VCPA-GA) and MLRAs are very effective in retrieving the LCC through hyperspectral reflectance at the leaf scale. The proposed methods could further provide some scientific basis for the hyperspectral remote sensing band setting of different platforms, such as an unmanned aerial vehicle (UAV) and satellite.

Apatinib combined with trastuzumab and albumin-bound paclitaxel for treatment of HER2+ breast cancer with brain metastases resistant to anti-HER2 TKIs: A case report.

Although human epidermal growth factor receptor 2 (HER2)-targeted therapy significantly improves the prognosis of patients with HER2-positive breast cancer, most patients with advanced breast cancer eventually progress due to drug resistance. At present, there is no standard treatment after patients become resistant to HER2-targeted therapy. Previous studies have indicated that anti-angiogenesis drugs have potential efficacy in the treatment of advanced breast cancer. The present study reported on a case of a pretreated patient with HER2-positive advanced breast cancer with brain metastases who developed resistance to multiple lines of HER2-targeted treatment. The patient was treated with apatinib combined with trastuzumab and albumin-bound paclitaxel. The patient achieved partial response to the third-line treatment with a progression-free survival of 9 months. After combination treatment, the symptoms of headache and vomiting were relieved and all the brain metastases were significantly reduced. The present case indicated that apatinib may have anti-tumor activity in patients with HER2-positive breast cancer with HER2-targeted drug resistance. The present case provides valuable information and may offer a new possibility for the treatment of patients with breast cancer with brain metastases who progressed after clinical treatment with small-molecule anti-HER2 tyrosine kinase inhibitor drugs.

CXCR4 inhibitor, AMD3100, down-regulates PARP1 expression and Synergizes with olaparib causing severe DNA damage in BRCA-proficient triple-negative breast cancer.

Poly ADP-ribose polymerase inhibitor (PARPi) treatment is effective in triple-negative breast cancer (TNBC) with BRCA mutation. However, its efficacy in BRCA-proficient TNBC remains unexplored. It is, therefore, an exciting proposition to broaden the indication of PARPi for BRCA-proficient TNBC patients. Chemokine receptor (CXCR4) is a transmembrane G protein-coupled receptor, which is involved in cell migration, proliferation, apoptosis, and damage repair, and it initiates many signalling pathways. Although administration of CXCR4 inhibitor alone is not ideal as a target drug, it can play a strong synergistic role in combination with other drugs. We explored the effect of CXCR4 and PARP1 on tumour cell proliferation, migration, metastasis, and apoptosis in vitro and in vivo and found that a CXCR4 inhibitor, AMD3100, enhanced the anti-tumour effect of PARP1 inhibitor, olaparib, on BRCA-proficient TNBC. When CXCR4 was inhibited and silenced, DNA damage repair and DNA replication fork activity were suppressed by up-regulating caspase-3-mediated increase in PARP1 cleavage; in combination with the inhibition of PARP1, AMD3100 resulted in the accumulation of fatal DNA damage and induction of apoptosis. This combination regimen can be effective against BRCA-proficient TNBC.

The bHLH transcription factor regulated gene OsWIH2 is a positive regulator of drought tolerance in rice.

Drought is a major abiotic stress limiting crop growth and yield. In this study, we characterized a novel drought tolerance induced WIH gene in rice, OsWIH2. Overexpression of OsWIH2 in rice resulted in significantly higher drought tolerance, probably due to the decreased water loss rate and reactive oxygen species (ROS) accumulation under drought stress. We identified a long-chain fatty acid HOTHEAD (HTH) that interacted with OsWIH2 using yeast two-hybrid screening. OsWIH2 is an enzyme which is involved in fatty acid synthesis. We further demonstrated that the drought-inducible bHLH transcription factor OsbHLH130 could activate the expression of OsWIH2. Overall, our results suggest that drought stress may induce OsbHLH130 accumulation, which in turn activates OsWIH2 expression, and the latter improves rice drought tolerance by participating in cuticular wax biosynthesis and reducing the water loss rate as well as ROS accumulation. This research provides new genes for crop improvement.

A small RNA of miR2119b from soybean CMS line acts as a negative regulator of male fertility in transgenic Arabidopsis.

The miR2119 is involved in the growth, development and abiotic stress response of some legumes, including Medicago truncatula, Phaseolus vulgaris and soybean (Glycine max (L.) Merr.). Our previous small RNA sequencing analysis showed that miR2119b was up-regulated in the flower buds of soybean cytoplasmic male sterile (CMS) line compared with its maintainer line, but the role and mechanism of miR2119b in the regulation of soybean male fertility are still unclear. In this study, the gma-miR2119b and its target gene alcohol dehydrogenase 1.3b (ADH1.3b) were characterized and found to be highly expressed in the flowers of soybean CMS line and its maintainer. Transgenic Arabidopsis plants overexpressing gma-miR2119b exhibit male fertility abnormalities, including pollen fertility and germination rate decreased. Enzyme activity detection found the ADH and catalase (CAT) enzyme activities in inflorescence of gma-miR2119b overexpressed plants were lower than those of wild-type. Bioinformatics and gene expression analysis showed that gma-miR2119b/GmADH1.3b module was responsive to high temperature (HT) stress during flowering. After HT stress, the gma-miR2119b overexpressed plants showed male sterility, including shorter filament, sterile pollen, indehiscent anther and non seed. Moreover, some key genes involved in HT response and reactive oxygen species (ROS) signal regulation pathway, including heat shock protein70, galactinol synthase 1 and CAT, showed down-regulated expression in transgenic plants under HT stress, suggesting that gma-miR2119b regulates male fertility via HT-ROS signaling pathway under HT stress. It was speculated that the gma-miR2119b acted as a negative regulator of male fertility in plants by regulating ADH1, HT-induced and ROS scavenging genes expression.

Heat-Responsive miRNAs Participate in the Regulation of Male Fertility Stability in Soybean CMS-Based F1 under High Temperature Stress.

MicroRNAs (miRNAs), a class of noncoding small RNAs (sRNAs), are widely involved in the response to high temperature (HT) stress at both the seedling and flowering stages. To dissect the roles of miRNAs in regulating male fertility in soybean cytoplasmic male sterility (CMS)-based F1 under HT, sRNA sequencing was performed using flower buds from HT-tolerant and HT-sensitive CMS-based F1 combinations (NF1 and YF1, respectively). A total of 554 known miRNAs, 59 new members of known miRNAs, 712 novel miRNAs, and 1145 target genes of 580 differentially expressed miRNAs (DEMs) were identified under normal temperature and HT conditions. Further integrated analysis of sRNA and transcriptome sequencing found that 21 DEMs and 15 differentially expressed target genes, such as gma-miR397a/Laccase 2, gma-miR399a/Inorganic phosphate transporter 1-4, and gma-miR4413a/PPR proteins, mitochondrial-like, were negatively regulated under HT stress. Furthermore, all members of the gma-miR156 family were suppressed by HT stress in both NF1 and YF1, but were highly expressed in YF1 under HT condition. The negative correlation between gma-miR156b and its target gene squamosa promoter-binding protein-like 2b was confirmed by expression analysis, and overexpression of gma-miR156b in Arabidopsis led to male sterility under HT stress. With these results, we proposed that miRNAs play an important role in the regulation of male fertility stability in soybean CMS-based F1 under HT stress.

Human Herpesvirus 6B U26 Inhibits the Activation of the RLR/MAVS Signaling Pathway.

U26 is one of the roseolovirus unique genes with unknown function. Human herpesvirus 6B (HHV-6B) pU26 is predicted to be an 8-transmembrane protein containing a mitochondrion location signal. Here, we analyzed U26 function during HHV-6B infection and find that (i) HHV-6B U26 is expressed at a very early stage during HHV-6B infection, and knockdown of it results in a significant decrease of HHV-6B progeny virus production; (ii) U26 inhibits the activation of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)/mitochondrial antiviral signaling protein (MAVS) signaling pathway, an important anti-HHV-6B infection innate immune response, by targeting MAVS protein for degradation; and (iii) a portion of U26 locates to the mitochondria, which could affect the mitochondrial membrane potential and finally leads to MAVS degradation. These findings indicate that HHV-6B U26 is a novel antagonistic viral factor against host innate antiviral immunity.IMPORTANCE HHV-6B (human herpesvirus 6B) is well known to evade host antiviral responses and establish a lifelong latent infection. How HHV-6B evades RNA recognition is still poorly understood. Our results indicate that HHV-6 U26 plays a vital role in RLR/MAVS signaling pathway activity. Knockout of endogenous MAVS could facilitate HHV-6B replication. The findings in this study could provide new insights into host-virus interactions and help develop a new therapy against HHV-6B infection.

Transcriptome analysis of Lactobacillus paracasei SMN-LBK under ethanol stress.

Lactobacillus paracasei SMN-LBK (serial number: CCTCC M 2017429) is an ethanol-resistant lactic acid bacteria (LAB) in kumiss. However, the anti-ethanol stress mechanism of L. paracasei SMN-LBK remains unclear. Hence, we performed a transcriptome analysis between L. paracasei SX10 (L. paracasei SMN-LBK under 10% ethanol stress strain, abbreviated as SX10) and L. paracasei SMN-LBK (abbreviated as S10) by RNA sequencing. We performed real-time quantitative PCR (RT-qPCR) to verify the accuracy of the transcription data. The transcriptome data revealed that 315 genes exhibited upregulated expression, and 332 genes were downregulated in the SX10 compared with the S10 group. The PFK, LDH, GPDH, and GK genes were upregulated, with a log2-fold change of 1.10, 0.30, 0.56, and 1.512, respectively. A gene ontology enrichment analysis revealed significant enrichment of ribosomes, ribonucleoprotein complex, non-membrane-bounded organelles, and intracellular non-membrane-bound organelles. Analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed differential genes associated with ribosome function, pyruvate metabolism, biosynthesis of amino acids, fatty acid biosynthesis, fatty acid metabolism, ATP-binding cassette (ABC) transporter, glycolysis, and glycerophospholipid metabolism. The RT-qPCR results were consistent with the transcriptome results. Lactococcus lactis NZ9000 is a typical host bacterium. We performed PFK and GK overexpression to verify the function of the L. paracaseiSX10 resistance gene in Lactococcus lactis NZ9000. Using sodium dodecyl sulfate (SDS)-PAGE electrophoresis, these resistance genes were successfully expressed in Lactococcus lactis NZ9000. The survival rate and key enzyme activity of the recombinant strains were determined under ethanol stress. The survival rate of Lactococcus lactis NZ9000-pNZ8148-PFK and Lactococcus lactis NZ9000-pNZ8148-GK under 10% ethanol stress were 3.43- and 3.80-fold higher compared with the Lactococcus lactis NZ9000-pNZ8148 control, respectively. These results indicate that PFK and GK are important for the ethanol tolerance of LAB and can increase the ethanol tolerance of Lactococcus lactis NZ9000. Hence, PFK and GK were identified as key genes of L. paracasei SX10 with a high ethanol tolerance. Our results provide novel insight for further studies to perform a systematic analysis of the differentially expressed genes and to determine their potential functions in the ethanol tolerance mechanism of LAB.

gp96 Is Critical for both Human Herpesvirus 6A (HHV-6A) and HHV-6B Infections.

Human herpesviruses 6A and 6B (HHV-6A and HHV-6B, respectively) are two virus species in the betaherpesvirus subfamily that exhibit T cell tropism. CD46 and CD134 are the cellular receptors for HHV-6A and HHV-6B, respectively. Interestingly, the efficiency of HHV-6A/6B entry is different among different types of target cells despite similar receptor expression levels on these cells. Here, we found that the cellular factor gp96 (also known as glucose-regulated protein 94 [GRP94]) is expressed on the cell surface and interacts with viral glycoprotein Q1 (gQ1) during virus entry. gp96 cell surface expression levels are associated with the efficiency of HHV-6A and HHV-6B entry into target cells. Both loss-of-function and gain-of-function experiments indicated that gp96 plays an important role in HHV-6 infection. Our findings provide new insight into the HHV-6 entry process and might suggest novel therapeutic targets for HHV-6 infection.IMPORTANCE Although new clinical importance has been revealed for human herpesviruses 6A (HHV-6A) and 6B, much is still unknown about the life cycles of these viruses in target cells. We identified a novel cellular factor, gp96, that is critical for both HHV-6A and -6B entry into host cells. As gp96 can function as an adjuvant in vaccine development for both infectious agents and cancers, it can be a potential therapeutic target for infection by these two viruses.

Long Noncoding RNA LINC00467 Promotes Glioma Progression through Inhibiting P53 Expression via Binding to DNMT1.

Purpose: This study aimed to investigate whether long noncoding RNA (lncRNA) LINC00467 could regulate proliferative and invasive abilities of glioma cells via p53 and DNA methyltransferase 1 (DNMT1), so as to participate in the occurrence and progression of glioma. Methods: LINC00467 expression in glioma was analyzed by GEPIA database and LINC00467 expression in glioma cell lines was detected by qRT-PCR. The regulatory effects of LINC00467 and p53 on proliferative, invasive capacities and cell cycle were conducted by CCK-8 and EdU assays, transwell assay and flow cytometry, respectively. The binding conditions between LINC00467, DNMT1 and p53 were determined by RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays. Western blot was conducted to determine whether LINC00467 could regulate p53 in glioma cells. Finally, rescue experiments were carried out to evaluate whether LINC00467 regulates proliferative and invasive abilities of glioma cells through p53. Results: The expression of LINC00467 was significantly up-regulated in tumor samples than that in normal samples, which was not correlated with patient survival time. Besides, expression of LINC00467 was higher in glioma cells than that of negative control cells. Upregulation of LINC00467 promoted proliferative and invasive abilities, and accelerated cell cycle in G0/G1 phase of U87 and LN229 cells. The results of RIP and ChIP assays demonstrated that LINC00467 could bind to DNMT1 and inhibit p53 expression. Overexpression of p53 partially reversed the enhancement of LINC00467 on proliferative and invasive abilities of glioma cells. Conclusion: These results indicated that high expression of LINC00467 could promote proliferative and invasive abilities of glioma cells through targeting inhibition of p53 expression by binding to DNMT1.

Simultaneous production of propionic acid and vitamin B12 from corn stalk hydrolysates by Propionibacterium freudenreichii in an expanded bed adsorption bioreactor.

Vitamin B12 and propionic acid that were simultaneous produced by Propionibacterium freudenreichii are both favorable chemicals widely used in food preservatives, medicine, and nutrition. While the carbon source and propionic acid accumulation reflected fermentation efficiency. In this study, using corn stalk as a carbon source and fed-batch fermentation process in an expanded bed adsorption bioreactor was studied for efficient and economic biosynthesis of acid vitamin B12 and propionic. With liquid hot water pretreated corn stalk hydrolysates as carbon source, 28.65 mg L-1 of vitamin B12 and 17.05 g L-1 of propionic acid were attained at 168 h in batch fermentation. In order to optimize the fermentation outcomes, fed-batch fermentation was performed with hydrolyzed corn stalk in expanded bed adsorption bioreactor (EBAB), giving 47.6 mg L-1 vitamin B12 and 91.4 g L-1 of propionic acid at 258 h, which correspond to product yields of 0.37 mg g-1 and 0.75 g g-1, respectively. The present study provided a promising strategy for economically sustainable production of vitamin B12 and propionic acid by P. freudenreichii fermentation using biomass cornstalk as carbon source and expanded bed adsorption bioreactor.

Isolation and Characterization of Ochrobactrum tritici for Penicillin V Potassium Degradation.

Substantial concentrations of penicillin V potassium (PVK) have been found in livestock manure, soil, and wastewater effluents, which may pose potential threats to human health and contribute to the emergence of penicillin-resistant bacterial strains. In this study, bacterial strains capable of degrading PVK were isolated from sludge and characterized. Strain X-2 was selected for biodegradation of PVK. Based on morphological observations and 16S rRNA gene sequencing, strain X-2 was identified as an Ochrobactrum tritici strain. To enhance the PVK degradation ability of PVK, a whole-cell biodegradation process of Ochrobactrum tritici X-2 was established and optimized. In the whole-cell biodegradation process, the optimal temperature and pH were 30°C and 7.0, respectively. Under the optimized conditions, the degradation rate using 0.5 mg/ml PVK reached 100% within 3 h. During biodegradation, two major metabolites were detected: penicilloic acid and phenolic acid. The present study provides a novel method for the biodegradation of PVK using Ochrobactrum tritici strains, which represent promising candidates for the industrial biodegradation of PVK.IMPORTANCE Substantial concentrations of penicillin V potassium (PVK) have been found in the environment, which may pose potential threats to human health and contribute to the emergence of penicillin-resistant bacterial strains. In this study, antibiotic-degrading bacterial strains for PVK were isolated from sludge and characterized. Ochrobactrum tritici was selected for the biodegradation of PVK with high efficiency. To enhance its PVK degradation ability, a whole-cell biodegradation process was established and optimized using Ochrobactrum tritici The degradation rate with 0.5 mg/ml PVK reached 100% within 3 h. The potential biodegradation pathway was also investigated. To the best of our knowledge, the present study provides new insights into the biodegradation of PVK using an Ochrobactrum tritici strain, a promising candidate strain for the industrial biodegradation of ß-lactam antibiotics.