Fed-batch fermentation strategy for efficient welan gum production by Sphingomonas sp. FM01.

BACKGROUND: As a novel type of extracellular polysaccharide produced by Sphingomonas sp., welan gum has been widely applied in various fields because of its excellent properties. The study has improved the fermentation process. RESULTS: The initial sucrose concentration, temperature and stirring speed were set to 20 g L-1, 33 °C and 400 rpm, respectively, and 13.3 g L-1 sucrose was added at 24, 40 and 56 h. The temperature and stirring speed were then set at 28 °C and 600 rpm from 24 to 48 h and 28 °C and 600 rpm from 48 to 72 h, respectively. As a result, welan gum production, dry cell weight, sucrose conversion rate and viscosity were correspondingly increased to 38.60 g L-1, 5.47 g L-1, 0.64 g g-1 and 3779 mPa·s, respectively. In addition, the mechanism by which fermentation strategy promotes welan gum synthesis was investigated by transcriptome analysis. CONCLUSION: Improving respiration and ATP supply, reducing unnecessary protein synthesis, and alleviating competition between cell growth and welan gum synthesis contribute to promoting the fermentation performance of Sphingomonas sp., thus providing a practical strategy for efficient welan gum production. © 2024 Society of Chemical Industry.

Assessment of the Safety and Exopolysaccharide Synthesis Capabilities of Bacillus amyloliquefaciens D189 Based on Complete Genome and Phenotype Analysis.

Exopolysaccharides (EPS) are natural macromolecular carbohydrates with good functional activity and physiological activities, which can be utilized as an emulsifier, viscosity enhancer, stabilizer, gelling agent, and water retention agent in a wide range of food products. In this study, the whole genome of Bacillus amyloliquefaciens D189, an EPS-producing bacteria, was sequenced. The result showed that D189 contains a single, circular chromosome of 3,963,356 bp with an average GC content of 45.74% and 3996 coding genes. The gene annotation results showed that D189 is a potentially safe strain and confirmed to be safe associated with hemolytic assay, and antibiotic resistance test. Meanwhile, D189 genome possessed 240 genes related to carbohydrate metabolism. More importantly, D189 could transport 9 sugars and contained a complete biosynthetic pathway for 8 nucleotide sugars. Based on the validation experiments, strain D189 could metabolize 8 sugars (glucose, sucrose, trehalose, fructose, cellobiose, maltose, mannitol, and N-acetyl-D-glucosamine) to produce EPS, with the highest yield of 1.212 g/L when sucrose was the carbon source. Therefore, the whole genome sequencing preliminarily elucidated the physiological mechanism of EPS, providing several pathways for engineering D189 to further enhance the yield of EPS.

Screening of the Lipid-Lowering Probiotic Lactiplantibacillus Plantarum SDJ09 and its Anti-Obesity Mechanism.

In this study, 39 strains of lactic acid bacteria were screened from several fermented foods. Based on the evaluation of functional and prebiotic properties, Lactiplantibacillus plantarum SDJ09 was selected as a promising candidate. It gave a 48.16% cholesterol reduction and 33.73% pancreatic lipase inhibition in cells; exhibited high resistance to acid, bile salts, and gastrointestinal fluid; and had strong antibacterial activity and high adhesion capabilities. More importantly, the lipid-lowering effect of L. plantarum SDJ09 was also investigated using 3T3-L1 mature adipocytes and HepG2 nonalcoholic fatty liver disease models. L. plantarum SDJ09 effectively decreased triglyceride accumulation by more than 50% in both cell models, in which the expression of PPARγ, C/EBPα, aP2, and LPL in 3T3-L1 cells was significantly downregulated by L. plantarum SDJ09. L. plantarum SDJ09 also improved lipid metabolism by downregulating the expression of HMGCR, SREBP-1c, ACC, and FAS and upregulating the expression of CYP7A1 in HepG2 nonalcoholic steatohepatitis cells. Therefore, L. plantarum SDJ09 has the potential to effectively decrease obesity and non-alcoholic fatty liver disease (NAFLD) by inhibiting lipid accumulation, providing a prospective probiotic agent for anti-obesity.

Presence of Epstein-Barr virus in cerebrospinal fluid is associated with increased mortality in HIV-negative cryptococcal meningitis.

Cryptococcus neoformans is the most common cause of fungal meningitis and is associated with a high mortality. The clinical significance of concurrent Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative patients with cryptococcal meningitis (CM) remains unclear. A retrospective cohort study was performed by analyzing CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA in these patients by metagenomic next-generation sequencing (mNGS) and compared 10-week survival rates among those with and without EBV DNA in CSF. Of the 79 CSF samples tested, 44.3% (35/79) had detectable viral DNA in CSF, while 55.7% (44/79) were virus-negative. The most frequent viral pathogen was EBV, which was detected in 22.8% (18/79) patients. The median number of CSF-EBV DNA reads was 4 reads with a range from 1 to 149 reads. The 10-week mortality rates were 22.2% (4/18) in those with positive CSF-EBV and 2.3% (1/44) in those with negative CSF-virus (hazard ratio 8.20, 95% confidence interval [CI] 1.52-81.80; P = 0.014), which remained significant after a multivariate adjustment for the known risk factors of mortality (adjusted hazard ratio 8.15, 95% CI 1.14-92.87; P = 0.037). mNGS can identify viruses that coexist in CSF of HIV-negative patients with CM. EBV DNA is most commonly found together with C. neoformans in CSF and its presence is associated with increased mortality in HIV-negative CM patients.

We retrospectively analyzed CSF samples from 79 HIV-negative Chinese Han patients with confirmed CM. We identified CSF viral DNA by mNGS and compared 10-week survival rates among those with and without EBV DNA. Positive CSF-EBV DNA is associated with the increased mortality in HIV-negative CM patients.

Xylitol fermentation characteristics with a newly isolated yeast Wickerhamomyces anomalus WA.

Xylitol is an increasingly popular functional food additive, and the newly isolated yeast Wickerhamomyces anomalus WA has shown extensive substrate utilization capability, with the ability to grow on hexose (d-galactose, d-glucose, d-mannose, l-fructose, and d-sorbose) and pentose (d-xylose and l-arabinose) substrates, as well as high tolerance to xylose at concentrations of up to 300 g/L. Optimal xylitol fermentation conditions were achieved at 32 °C, 140 rpm, pH 5.0, and initial cell concentration OD600 of 2.0, with YP (yeast extract 10 g/L, peptone 20 g/L) as the optimal nitrogen source. Xylitol yield increased from 0.61 g/g to 0.91 g/g with an increase in initial substrate concentration from 20 g/L to 180 g/L. Additionally, 20 g/L glycerol was found to be the optimal co-substrate for xylitol fermentation, resulting in an increase in xylitol yield from 0.82 g/g to 0.94 g/g at 140 rpm, enabling complete conversion of xylose to xylitol.

Developmental relationship between junctional epithelium and epithelial rests of Malassez.

Keratin 17 (K17) is thought to be a candidate target gene for regulation by Lymphoid Enhancer Factor-1 (Lef-1). K17 is a marker that distinguishes junctional epithelium (JE) from epithelial rests of Malassez (ERM). However, the relationship of Lef-1 to K17 is not clear in this context. Moreover, the expression of other keratins such as K5, K6, K7 and K16 is not reported. Therefore, the aim of our study was to assay the expression of K5, K6, K7, K14, K16, K17 and Lef-1 in postnatal developing teeth, and clarify the corresponding immunophenotypes of the JE and ERM. Upper jaws of Wistar rats aged from postnatal (PN) day 3.5 to PN21 were used and processed for immunohistochemistry. K5 and K14 were intensely expressed in inner enamel epithelium (IEE), reduced enamel epithelium (REE), ERM and JE. There was no staining for K16 in the tissue, except for strong staining in the oral epithelium. Specifically, at PN3.5 and PN7, K17 was initially strongly expressed and then negative in the IEE. At PN16 and PN21, both REE and ERM were strongly stained for K17, whereas K17 was negative in the JE. In addition, K6, K7 and Lef-1 were not detected in any tissue investigated. REE and ERM have an identical keratin expression pattern before eruption, while JE differs from ERM in the expression of K17 after eruption. The expression of K17 does not coincide with that of Lef-1. These data indicate that JE has a unique phenotype different from ERM, which is of odontogenic origin.

Bifidobacterium breve Protects the Intestinal Epithelium and Mitigates Inflammation in Colitis via Regulating the Gut Microbiota-Cholic Acid Pathway.

In this study, we aimed to explore the protective effects of Bifidobacterium in colitis mice and the potential mechanisms. Results showed that Bifidobacterium breve (B. breve) effectively colonized the intestinal tract and alleviated colitis symptoms by reducing the disease activity index. Moreover, B. breve mitigated intestinal epithelial cell damage, inhibited the pro-inflammatory factors, and upregulated tight junction (TJ)-proteins. Gut microbiota and metabolome analysis found that B. breve boosted bile acid-regulating genera (such as Bifidobacterium and Clostridium sensu stricto 1), which promoted bile acid deconjugation in the intestine. Notably, cholic acid (CA) was closely associated with the expression levels of inflammatory factors and TJ-proteins (p < 0.05). Our in vitro cell experiments further confirmed that CA (20.24 ± 4.53 pg/mL) contributed to the inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression (49.32 ± 5.27 pg/mL) and enhanced the expression of TJ-proteins (Occludin and Claudin-1) and MUC2. This study suggested that B. breve could be a probiotic candidate for use in infant foods.

High-Level Extracellular Expression of Hyaluronate Lyase HylP in Bacillus subtilis for Hyaluronan Degradation.

Hyaluronate lyase (HA lyase) has potential in the industrial processing of hyaluronan. In this study, HylP, an HA lyase from Streptococcus pyogenes phage (SPB) was successfully expressed in Bacillus subtilis. To improve the extracellular enzyme activity of HylP in B. subtilis, signal peptide engineering systematic optimization was carried out, and cultured it from shake flasks and fermenters, followed by purification, characterization, and analysis of degradation products. The results showed that the replacement of the signal peptide increased the extracellular enzyme activity of HylP from 1.0 × 104 U/mL to 1.86 × 104 U/mL in the shake flask assay, and using a 20 L fermenter in a batch fermentation process, the extracellular enzyme activity achieved the level of 1.07 × 105 U/mL. HylP exhibited significant thermal and pH stability in the temperature range of 40 °C and pH range of 4-8, respectively. The enzyme showed optimum activity at 40 °C and pH 6, with significant activity in the presence of Na+, Mg2+, and Co2+ ions. Degradation analysis showed that HylP efficiently degraded hyaluronan as an endonuclease, releasing unsaturated disaccharides. These comprehensive findings underscore the substantial industrial potential of HylP for hyaluronan processing applications, offering valuable insights into enzyme characterization and optimization of expression for potential industrial utilization.

Structural insights of a SusD-like protein in marine Bacteroidetes bacteria reveal the molecular basis for chitin recognition and acquisition.

Efficient recognition and transportation of chitin oligosaccharides are crucial steps for the utilization of chitin by heterotrophic bacteria. In this study, we employed structural biological and biochemical approaches to investigate the substrate recognition and acquisition mechanism of a novel chitin-binding SusD-like protein, AqSusD, which is derived from the chitin utilization gene cluster of a marine Bacteroides strain (Aquimarina sp. SCSIO 21287). We resolved the crystal structures of the AqSusD apo-protein and its complex with chitin oligosaccharides. Our results revealed that some crucial residues (Gln67, Phe87, and Asp276) underwent significant conformational changes to form tighter substrate binding sites for ligand binding. Moreover, we identified the functions of key amino acid residues and discovered that π-π stacking and hydrogen bonding between AqSusD and the ligand played significant roles in recognition of the protein for chitin oligosaccharide binding. Based on our findings and previous investigations, we put forward a model for the mechanism of chitin oligosaccharide recognition, capture, and transport by AqSusD, in collaboration with the membrane protein AqSusC. Our study deepens the understanding of the molecular-level "selfish" use of polysaccharides such as chitin by Bacteroides.

Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors with the highest incidence and mortality in the world, causing a serious burden on society. Pyruvate kinase M2 (PKM2) is one of the principal metabolic enzymes involved in glycolysis. Studies have shown that PKM2 is highly expressed in HCC and can be translocated to the nucleus, where it interacts with various transcription factors and proteins such as hypoxia-inducible factor-1α, sterol regulatory element-binding protein 1a, signal transducer and activator of transcription 3, nuclear factor erythroid 2-like 2 and histone H3, exerting non-metabolic enzyme functions to regulate the cell cycle, proliferation, apoptosis, immune escape, migration, and invasion, as well as HCC angiogenesis and tumor microenvironment. This review is focused on the recent progress of PKM2 interacting with various transcription factors and proteins affecting the onset and development of HCC, as well as natural drugs and noncoding RNA impacting diverse biological functions of liver cancer cells by regulating PKM2 non-metabolic enzyme functions, thereby providing valuable directions for the prognosis improvement and molecular targeted therapy of HCC in the future.

Isolation, identification, and preparation of tyrosinase inhibitory peptides from Pinctada martensii meat.

Recently, natural tyrosinase inhibitors have gained attention in clinical cosmetology research. In this study, the enzymatic hydrolysis of Pinctada martensii meat by protease from Bacillus licheniformis, 401 peptides with tyrosinase inhibitory were identified after isolated by ultrafiltration and Sephadex G-15 from the fraction F4. The peptide effects on the tyrosinase activity and structure were evaluated using molecular docking. Three synthetic peptides classified as W1 (WDRPKDDGGSPIK), W2 (DRGYPPVMF), and W3 (SGGGGGGGLGSGGSIRSSY), which had the lowest binding energies were selected for in vitro synthesis and biological activity investigation. The W3 peptide (5 mg/mL) had the highest tyrosinase activity, SPF, DPPH, and ABTS clearance values, and total antioxidant capacity. W3 did not affect the survival rate of mouse melanoma B16-F10 cells (1.0-5.0 mg/mL) but decreased the melanin content. Hence, W3 could be suitable for multifunctional tyrosinase inhibition and provides a novel method to use marine organisms as natural tyrosinase inhibitor sources.

In-Situ Study on the Tensile Deformation and Fracture Mechanism of a Bimodal-Structured Mg-Gd-Y Alloy.

The as-extruded (EX) Mg-Gd-Y alloy studied here exhibited a bimodal structure, composed of fine dynamic recrystallized (DRXed) grains with random orientations and longitudinal coarse hot-worked grains. The slip analysis showed the DRXed grains exhibited mainly basal slips, while the hot-worked grains exhibited mainly prismatic slips during the tensile deformation. The distribution of geometrically necessary dislocations (GNDs) showed that there was strain partitioning between the fine and coarse grain regions. The hetero-deformation induced (HDI) hardening occurred between the two domains. It improves the strength and strain hardening capability of the alloy, leading to good strength-ductility synergy. Microcracks tended to nucleate at the DRXed grain boundaries, as well as at the interface between the two domains. The calculation of geometric compatibility parameter (m') indicated that strain incompatibility between the adjacent grains induced the crack nucleation. The toughening effect of the fine DRXed grains hindered the crack propagation. However, the major crack formed at the interface between the two domains propagated unstably, due to the high stress concentration and the large crack size, causing the final failure.

PSME3 induces radioresistance and enhances aerobic glycolysis in cervical cancer by regulating PARP1.

Cervical cancer (CC) ranks the fourth in gynecologic cancers. The incidence and mortality of CC has been decreased due to the cancer screening and early treatments in recent years, but the prognosis of CC patients at advanced stage is still sorrowful. Whether PSME3 exerted a role in the radioresistance of CC cells remains to be investigated. In this study, the expression of PSME3 in mRNA and protein levels was measured by RT-qPCR and western blot analysis, and increased expression of PSME3 in CC tissues and cells was observed. CCK-8 and colony formation assay revealed that the cell viability and proliferation of Hela and CaSki cells treated with different doses of X-ray was reduced due to the depletion of PSME3, indicating that silencing of PSME3 enhanced the radiosensitivity of CC cells. In addition, repair on DNA damage in CC cells was enhanced by PSME3 and the damage was attenuated by PSME3. Besides, the expression of glycolysis-related proteins (GLUT1, PGC-1α, LDHA and HK2) were enhanced by PSME3 but reduced by silencing PSME3 in CC cells. PSME3 restraint attenuated the levels of glucose consumption and lactate production, suggesting PSME3 depletion suppressed abnormal glycolysis of CC cells. Mechanically, PSME3 increased the PARP1 expression via elevating c-myc. Finally, we observed PSME3 attenuation inhibited CC growth in vivo. In conclusion, PSME3 enhanced radioresistance and aerobic glycolysis in CC by regulating PARP1, which might shed a light into the function of PSME3 in CC treatment.

Maslinic acid alleviates LPS-induced mice mastitis by inhibiting inflammatory response, maintaining the integrity of the blood-milk barrier and regulating intestinal flora.

Mastitis occurs frequently in breastfeeding women and not only affects the women's health but also hinders breastfeeding. Maslinic acid is a type of pentacyclic triterpenoid widely found in olives that has good anti-inflammatory activity. This study aims to discuss the protective function of maslinic acid against mastitis and its underlying mechanism. For this, mice models of mastitis were established using lipopolysaccharide (LPS). The results revealed that maslinic acid reduced the pathological lesions in the mammary gland. In addition, it reduced the generation of pro-inflammatory factors and enzymes (IL-6, IL-1ß, TNF-α, iNOS, and COX2) in both mice mammary tissue and mammary epithelial cells. The high-throughput 16S rDNA sequencing of intestinal flora showed that in mice with mastitis, maslinic acid treatment altered ß-diversity and regulated microbial structure by increasing the abundance of probiotics such as Enterobacteriaceae and downregulating harmful bacteria such as Streptococcaceae. In addition, maslinic acid protected the blood-milk barrier by maintaining tight-junction protein expression. Furthermore, maslinic acid downregulated mammary inflammation by inhibiting the activation of NLRP3 inflammasome, AKT/NF-κB, and MAPK signaling pathways. Thus, in a mice model of LPS-induced mastitis, maslinic acid can inhibit the inflammatory response, protect the blood-milk barrier, and regulate the constitution of intestinal flora.

Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133+ cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133+ cells compared to CD133- cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.

Hot Cracking Behaviors of Mg-Zn-Er Alloys with Different Er Contents.

The hot cracking behaviors of Mg-5Zn-xEr (x = 0.83, 1.25, 2.5, 5 wt.%) alloys are investigated by optimized hot cracking experimental apparatus, optical microscope, and scanning electron microscope, such as contraction behaviors, feeding behaviors, and permeability characteristics. It is found that the solid phase fraction at hot crack initiation and within the freezing range both increased with increasing Er contents up to 2.5 wt.% and then decreased at 5 wt.% Er content. The Mg-5Zn-5Er alloy exhibits the lowest solid phase fraction (87.4%) and a reduced freezing range (74.2 °C), which leads to more effective liquid feeding in the latter stages of solidification. Combined with the grain size, the permeability of the mushy zone, and fracture morphology, the overall permeability is optimal in the Mg-5Zn-5Er alloy, which is beneficial for feeding the cavities and micro-pores. Meanwhile, a large amount of W phase precipitated by the eutectic reaction (L→α-Mg + W phase), which facilitates healing of the incurred cracking. Conversely, the Mg-5Zn-2.5Er alloy shows inferior feeding ability due to the lowest solid phase fraction (98.3%), wide freezing range (199.5 °C), and lowest permeability. Therefore, the Mg-5Zn-2.5Er alloy exhibits maximal hot cracking susceptibility, and the Mg-5Zn-5Er alloy exhibits minimal hot cracking susceptibility. This work provides guidance for improving the hot cracking resistance of cast Mg-Zn-Er alloy and enables an understanding of the hot cracking behaviors of Mg-Zn-RE alloys.

Temperal and spatial expression of CCN1, CCN3, CCN4, CCN5 and CCN6 proteins in the developing postnatal teeth.

CCN proteins are matricellular proteins and are important modulators of development and function of adult organs. However, there is no literature reporting the localization of CCN proteins during postnatal tooth development and the formation of periodontium. Therefore, the aim of our study was to investigate the expression of CCN1, CCN3, CCN4, CCN5 and CCN6 in the developing postnatal teeth. Wistar rats were used at postnatal (PN) 3.5, 7, 16 and 21 days and maxillas were processed for immunohistochemistry. At PN3.5 and PN7, preameloblasts (PA), secretory ameloblasts (SA), odontoblasts (OD) and dental pulp (DP) showed moderate to strong staining for CCN1, CCN4 and CCN6 respectively. CCN5 was intensely expressed in predentin, whereas CCN5 was undetectable in PA, SA, OD and DP. At PN16 and PN21, moderate to strong reaction with CCN1, CCN4 and CCN6 was evident in OD, DP, reduced enamel epithelium (REE), osteoblasts (OB) and periodontal ligament (PDL) respectively, while CCN5 was negative to weakly expressed in REE, OD, DP, OB, PDL and osteocytes (OC). Interestingly, the expression of CCN1, CCN4 and CCN6 was initially negative at PN16 but strong at PN21 in OC. Furthermore, there was no staining for CCN3 in the tissues studied. These results demonstrated that the expression pattern of CCN1, CCN4 and CCN6 is similar and inversely correlated with that of CCN3. CCN5 exhibits a unique distribution pattern. These data indicate that CCN proteins might play regulatory roles in amelogenesis, dentinogenesis, osteogenesis and PDL homeostasis.

Microstructure and Mechanical Properties of Magnesium Matrix Composites Reinforced by In Situ Reduced Graphene Oxide.

Due to their excellent mechanical properties and large specific surface area, graphene and its derivatives are widely used in metal matrix composites as reinforcements. In this study, the thermal reduction behavior of large-size graphene oxide are investigated systematically, and reduced graphene oxide (RGO) with few residual oxygen groups and good structural integrity is obtained. ZK61 matrix composites with varying content of in situ RGO are fabricated using the semi-powder metallurgy method. The results reveal that the addition of RGO can cause the refinement of the grains and the second phase, which is attributed to the uniform distribution of the RGO throughout the matrix. The formation of nano-MgO particles is beneficial in increasing the interfacial bonding strength between the RGO and the matrix, resulting in simultaneous increments in yield strength and elongation in the RGO/ZK61 composites. The composite containing 0.6 wt.% RGO shows a superior mechanical property, including microhardness of 79.9 HV, yield strength of 203 MPa and excellent elongation of 17.5%, with increases of 20.9%, 8.6% and 7.4%, respectively, when compared with the ZK61 alloy. Quantitative analysis indicates that the main strengthening mechanisms of RGO-reinforced magnesium matrix composites are load transfer strengthening and grain refinement strengthening.

Enzymatic biotransformation of Rb3 from the leaves of Panax notoginseng to ginsenoside rd by a recombinant ß-xylosidase from Thermoascus aurantiacus.

Given the important pharmacological activity of ginsenoside Rd but its low content in plants, the production of Rd by enzymatic transformation is of interest. In this study, a ß-xylosidase gene Ta-XylQS from Thermoascus aurantiacus was cloned and overexpressed in Komagataella phaffii. Purified recombinant Ta-XylQS specifically hydrolyzes substrates with xylosyl residues at the optimal pH of 3.5 and temperature of 60 °C. This study established a process for producing Rd by transforming ginsenoside Rb3 in the saponins of Panax notoginseng leaves via recombinant Ta-XylQS. After 60 h, 3 g L- 1 of Rb3 was transformed into 1.46 g L- 1 of Rd, and the maximum yield of Rd reached 4.31 g kg- 1 of Panax notoginseng leaves. This study is the first report of the biotransformation of ginsenoside Rb3 to Rd via a ß-xylosidase, and the established process could potentially be adopted for the commercial production of Rd from Rb3.

Remodeling tumor microenvironment with natural products to overcome drug resistance.

With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance.