Deubiquitinating enzyme USP28 inhibitor AZ1 alone and in combination with cisplatin for the treatment of non-small cell lung cancer.

Lung cancer is one of the most common malignant tumors. Despite decades of research, the treatment of lung cancer remains challenging. Non-small cell lung cancer (NSCLC) is the primary type of lung cancer and is a significant focus of research in lung cancer treatment. The deubiquitinase ubiquitin-specific protease 28 (USP28) plays a role in the progression of various tumors and serves as a potential therapeutic target. This study aims to determine the role of USP28 in the progression of NSCLC. We examined the impact of the USP28 inhibitor AZ1 on the cell cycle, apoptosis, DNA damage response, and cellular immunogenicity in non-small cell lung cancer. We observed that AZ1 and siUSP28 induce DNA damage, leading to the activation of Noxa-mediated mitochondrial apoptosis. The dsDNA and mtDNA released from DNA damage and mitochondrial apoptosis activate tumor cell immunogenicity through the cGAS-STING signaling pathway. Simultaneously, targeting USP28 promotes the degradation of c-MYC, resulting in cell cycle arrest and inhibition of DNA repair. This further promotes DNA damage-induced cell apoptosis mediated by the Noxa protein, thereby enhancing tumor cell immunogenicity mediated by dsDNA and mtDNA. Moreover, we found that the combination of AZ1 and cisplatin (DDP) can enhance therapeutic efficacy, thereby providing a new strategy to overcome cisplatin resistance in NSCLC. These findings suggest that targeting USP28 and combining it with cisplatin are feasible strategies for treating NSCLC.

Realizing High Thermoelectric Properties in Bi2S3 Bulk via Band Engineering and Nanorods Compositing.

Bismuth sulfide is a promising thermoelectric material because of its low cost and toxicity; however, its low electrical conductivity limits its thermoelectric properties. In this study, Bi2S3+x wt% HfCl4 (x = 0, 0.25, 0.5, 0.75, and 1.0) bulk samples are fabricated using a combination of melting and spark plasma sintering. The microstructures, electronic structures, and thermoelectric properties of the composites are characterized. The results of electronic structure calculations show that doping with HfCl4 produces an impurity energy level that narrows the bandgap and allows the Fermi energy level to enter the conduction band, leading to a favorable increase in carrier concentration. By regulating the HfCl4 doping concentration, the electrical conductivity of the 0.75 wt% doped sample reaches 253 Scm-1 at 423 K and its maximum ZT value is 0.47 at 673 K. Moreover, the sample is compounded with Bi2S3 nanorods prepared by the hydrothermal method, reducing thermal conductivity by 30% due to the introduction of additional interfaces and pores. This resulted in a final ZT value of 0.61 at 673 K, which is approximately eight times higher than that of pure Bi2S3. This step-by-step optimization approach provides a valuable methodology for enhancing the performance of other thermoelectric material systems.

Spatiotemporal analysis and seasonality of tuberculosis in Pudong New Area of Shanghai, China, 2014-2023.

BACKGROUND: Spatiotemporal analysis is a vital method that plays an indispensable role in monitoring epidemiological changes in diseases and identifying high-risk clusters. However, there is still a blank space in the spatial and temporal distribution of tuberculosis (TB) incidence rate in Pudong New Area, Shanghai. Consequently, it is crucial to comprehend the spatiotemporal distribution of TB in this district, this will guide the prevention and control of TB in the district. METHODS: Our research used Geographic Information System (GIS) visualization, spatial autocorrelation analysis, and space-time scan analysis to analyze the TB incidence reported in the Pudong New Area of Shanghai from 2014 to 2023, and described the spatiotemporal clustering and seasonal hot spot distribution of TB incidence. RESULTS: From 2014 to 2023, the incidence of TB in the Pudong New Area decreased, and the mortality was at a low level. The incidence of TB in different towns/streets has declined. The spatial autocorrelation analysis revealed that the incidence of TB was spatially clustered in 2014, 2016-2018, and 2022, with the highest clusters in 2014 and 2022. The high clustering area was mainly concentrated in the northeast. The space-time scan analysis indicated that the most likely cluster was located in 12 towns/streets, with a period of 2014-2018 and a radiation radius of 15.74 km. The heat map showed that there was a correlation between TB incidence and seasonal variations. CONCLUSIONS: From 2014 to 2023, the incidence of TB in the Pudong New Area of Shanghai declined, but there were spatiotemporal clusters and seasonal correlations in the incidence area. Local departments should formulate corresponding intervention measures, especially in high-clustering areas, to achieve accurate prevention and control of TB within the most effective time and scope.

Sensitivity influencing factors during pesticide residue detection research via a terahertz metasensor.

Two metamaterial sensors were designed to test three pesticide residues. The influences of the metamaterial structure, the analyte composition and volume on the sensitivity have been studied. The metamaterial field-enhancement ability has an important influence on the sensitivity within the high-concentration range, while the coincidence between the metamaterial resonant frequency and the analyte fingerprint peak plays a dominant role within the low-concentration range. These findings allow us to better understand the process and find a way to improve the sensitivity.

Self-Healing Silicone Elastomer with Stable and High Adhesion in Harsh Environments.

Adhesive and self-healing elastomers are urgently needed for their convenience and intelligence in biological medicine, flexible electronics, intelligent residential systems, etc. However, their inevitable use in harsh environments results in further enhancement requirements of the structure and performance of adhesive and self-healing elastomers. Herein, a novel self-healing and high-adhesion silicone elastomer was designed by the synergistic effect of multiple dynamic bonds. It revealed excellent stretchability (368%) and self-healing properties at room temperature (98.1%, 5 h) and in a water environment (96.4% for 5 h). Meanwhile, the resultant silicone elastomer exhibited high adhesion to metal and nonmetal and showed stable adhesion in harsh environments, such as under acidic (pH 1) and alkaline (pH 12) environments, salt water, petroleum ether, water, etc. Furthermore, it was applied as a shatter-proof protective layer and a rust-proof coating, proving its significant potential in intelligent residential system applications.

TruNeo: an integrated pipeline improves personalized true tumor neoantigen identification.

BACKGROUND: Neoantigen-based personal vaccines and adoptive T cell immunotherapy have shown high efficacy as a cancer treatment in clinical trials. Algorithms for the accurate prediction of neoantigens have played a pivotal role in such studies. Some existing bioinformatics methods, such as MHCflurry and NetMHCpan, identify neoantigens mainly through the prediction of peptide-MHC binding affinity. However, the predictive accuracy of immunogenicity of these methods has been shown to be low. Thus, a ranking algorithm to select highly immunogenic neoantigens of patients is needed urgently in research and clinical practice. RESULTS: We develop TruNeo, an integrated computational pipeline to identify and select highly immunogenic neoantigens based on multiple biological processes. The performance of TruNeo and other algorithms were compared based on data from published literature as well as raw data from a lung cancer patient. Recall rate of immunogenic ones among the top 10-ranked neoantigens were compared based on the published combined data set. Recall rate of TruNeo was 52.63%, which was 2.5 times higher than that predicted by MHCflurry (21.05%), and 2 times higher than NetMHCpan 4 (26.32%). Furthermore, the positive rate of top 10-ranked neoantigens for the lung cancer patient were compared, showing a 50% positive rate identified by TruNeo, which was 2.5 times higher than that predicted by MHCflurry (20%). CONCLUSIONS: TruNeo, which considers multiple biological processes rather than peptide-MHC binding affinity prediction only, provides prioritization of candidate neoantigens with high immunogenicity for neoantigen-targeting personalized immunotherapies.

Correlations of Inflammatory Factors with Intestinal Flora and Gastrointestinal Incommensurate Symptoms in Children with Asthma.

BACKGROUND Bronchial asthma is a common pediatric disease, the pathogenesis of which is complicated. The correlations of the levels of inflammatory factors in peripheral serum with intestinal flora and gastrointestinal incommensurate symptoms in children with asthma remain to be further elucidated. MATERIAL AND METHODS A total of 70 children diagnosed with asthma in the Pediatric Department of our hospital from February 2016 to March 2017 were enrolled as an observation group, and another 25 healthy children in the same age range were selected as a control group. The levels of inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], the total load of intestinal flora, and the main strains were detected among all included patients. Moreover, incommensurate symptoms of patients in the observation group were recorded and gastrointestinal symptom rating scale (GSRS) scores were calculated. The differences in indexes between the observation group and the control group were compared. RESULTS The levels of CRP, TNF-α, and IL-6 in peripheral serum in the observation group were significantly higher than those in the control group (p<0.05). The analysis of the correlations of inflammatory factors in peripheral serum with intestinal flora and GSRS scores showed that C-reactive protein (CRP) was positively correlated with GSRS scores (r=0.696, p<0.001) and the total load of intestinal bacteria (r=0.813, p<0.001). CONCLUSIONS The inflammatory factors in peripheral serum of children with asthma are closely correlated with intestinal flora and gastrointestinal function. With the increasingly high levels of inflammatory factors in peripheral serum, the probability of intestinal flora disturbance and gastrointestinal incommensurate symptoms will be increased.

Biosynthesis of D-lactic acid from lignocellulosic biomass.

D-lactic acid is a versatile and important industrial chemical that can be applied in the synthesis of thermal-resistant poly-lactic acid. Biosynthesis of D-lactic acid can be achieved by a variety of microorganisms, including lactic acid bacteria, yeast, and fungi; however, the final product yield, optical purity, and the utilization of both glucose and xylose are restricted. Consequently, engineered microbial systems are essential to attain high titer, productivity, and complete utilization of sugars. Herein, we critically evaluate the promising wild-type microorganisms, as well as genetically modified microorganisms to produce enantiomerically pure D-lactic acid, particularly from renewable lignocellulosic biomass. In addition, innovative bioreactor operation, metabolic flux analysis, and recent genetic engineering methods for targeted microbial D-lactic acid synthesis will be discussed.

Enhanced D-lactic acid production from renewable resources using engineered Lactobacillus plantarum.

D-lactic acid is used as a monomer in the production of poly-D-lactic acid (PDLA), which is used to form heat-resistant stereocomplex poly-lactic acid. To produce cost-effective D-lactic acid by using all sugars derived from biomass efficiently, xylose-assimilating genes encoding xylose isomerase and xylulokinase were cloned into an L-lactate-deficient strain, Lactobacillus plantarum. The resulting recombinant strain, namely L. plantarum NCIMB 8826 ∆ldhL1-pLEM-xylAB, was able to produce D-lactic acid (at optical purity >99 %) from xylose at a yield of 0.53 g g(-1). Simultaneous utilization of glucose and xylose to produce D-lactic acid was also achieved by this strain, and 47.2 g L(-1) of D-lactic acid was produced from 37.5 g L(-1) glucose and 19.7 g L(-1) xylose. Corn stover and soybean meal extract (SBME) were evaluated as cost-effective medium components for D-lactic acid production. Optimization of medium composition using response surface methodology resulted in 30 % reduction in enzyme loading and 70 % reduction in peptone concentration. In addition, we successfully demonstrated D-lactic acid fermentation from corn stover and SBME in a fed-batch fermentation, which yielded 61.4 g L(-1) D-lactic acid with an overall yield of 0.77 g g(-1). All these approaches are geared to attaining high D-lactic acid production from biomass sugars to produce low-cost, highly thermostable biodegradable plastics.

Tuberculosis-associated mortality in Shanghai, China: a longitudinal study.

OBJECTIVE: To determine excess mortality in a cohort of people with tuberculosis in Shanghai. METHODS: Participants were local residents in 4 (of 19) districts in Shanghai, registered in one of four tuberculosis clinics between January 1, 2004 and December 31, 2008. Baseline data were collected at the most recent diagnosis of tuberculosis and mortality was assessed between March and May of 2014. We calculated standardized mortality ratios (SMR) and case-fatality rates for all participants and for subgroups. Univariate and multivariate Cox regression models were used to quantify associations between co-morbidities and mortality from all causes and from tuberculosis. FINDINGS: We registered 4569 subjects in the cohort. Overall, the cohort had an SMR for deaths from all causes of 5.2 (95% confidence interval, CI: 4.8-5.6). Males had a higher SMR than females (6.1 versus 3.0). After adjustment for age and sex, hazard ratios (HR) for deaths from all causes were significantly greater in previously treated people (HR: 1.26; 95% CI: 1.08-1.49) and sputum smear-test positive people (HR: 1.55; 95% CI: 1.35-1.78). The risk of death from tuberculosis was also significantly greater for previously treated people (HR: 1.88; 95% CI: 1.24-2.86) and smear positive people (HR: 3.16; 95% CI: 2.06-4.87). CONCLUSION: People with tuberculosis in Shanghai have an increased risk of mortality. Earlier diagnosis and more vigilant follow-up may help to reduce mortality in this group.

Estimation of high risk pregnancy contributing to perinatal morbidity and mortality from a birth population-based regional survey in 2010 in China.

BACKGROUND: Neonatal mortality reduction in China over past two decades was reported from nationwide sampling surveys, however, how high risk pregnancy affected neonatal outcome is unknown. The objective of this study was to explore relations of pregnancy complications and neonatal outcomes from a regional birth population. METHODS: In a prospective, cross-sectional survey of complete birth population-based data file from 151 level I-III hospitals in Huai'an region in 2010, pregnancy complications were analyzed for perinatal morbidity and mortality in association with maternal and perinatal characteristics, hospital levels, mode of delivery, newborn birth weight and gestational age, using international definition for birth registry and morbidities. RESULTS: Pregnancy complications were found in 10% of all births, in which more than 70% were delivered at level II and III hospitals associated with higher proportions of fetal and neonatal death, preterm birth, death at delivery and congenital anomalies. High Cesarean section delivery was associated with higher pregnancy complications, and more neonatal critical illnesses. The pregnancy complications related perinatal morbidity and mortality in level III were 2-4 times as high as in level I and II hospitals. By uni- and multi-variate regression analysis, impact of pregnancy complications was along with congenital anomalies and preterm birth, and maternal child-bearing age and school education years contributing to the prevalence. CONCLUSIONS: This survey revealed variable links of pregnancy complications to perinatal outcome in association with very high Cesarean section deliveries, which warrants investigation for causal relations between high risk pregnancy and neonatal outcome in this emerging region.

An epidemiologic survey of pediatric sepsis in regional hospitals in China.

OBJECTIVE: To determine the prevalence, treatment, and outcomes of sepsis at regional hospitals in Huai'an, Jiangsu, China. DESIGN: Prospective data registry using a descriptive clinical epidemiologic approach through a collaborative network. SETTING: Pediatric departments in 11 regional city and county referral hospitals serving 843,000 children (exclusive of neonates). SUBJECTS: All admissions (n = 27,836) of patients from 28 days to 15 years old from September 1, 2010, to August 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,530 patients met the 2005 international consensus definition of sepsis, corresponding to an estimated incidence of 181/100,000 children, with 80% under 5 years old, and in 10% (153), severe sepsis or septic shock developed. The overall case fatality rate for sepsis was 3.5% (53/1,530) or 34.6% (53/153) in those in whom severe sepsis or septic shock developed. Treatment varied widely and in many instances did not conform to international guidelines as reflected by inadequate use of antibiotics, corticosteroids, vasoactive agents, and inotropes. CONCLUSIONS: We first report the prevalence and outcome of pediatric sepsis based on a regional hospital network in China. The diverse treatment approaches and practice at low-level clinics suggest the need for clinical implementation of internationally recognized strategy to improve the care standard in resource-limited regional hospitals.

A noninvasive measurement technique for the initial stiffness of the radial artery.

Arterial stiffness carries significant implications for cardiovascular disease. Monitoring changes in arterial stiffness is integral to proactive health management, however, current noninvasive methods of quantifying stiffness in vivo rely primarily on linear tangent stiffness, making the measurements vulnerable to the variability of blood pressure and thereby affecting the accuracy in portraying the health status of the arteries. This study proposed a novel methodology for evaluating arterial stiffness that is unaffected by changes in blood pressure. Ultrasound detection techniques are applied to accurately chronicle changes in radial artery diameters across varied blood pressures. Incorporating blood pressure measurements, the initial diameter at cuff blockade, and vessel diameters at systolic and diastolic pressures enables inverse determination of the unstressed initial radial artery stiffness. This method accurately mirrors the results of in vitro experiments employing porcine blood vessels at physiological pressures. The results underscore the technique's ability to quantify arterial mechanical properties precisely. This study offers a groundbreaking strategy for fostering the early detection of atherosclerosis, and aiding artery health regulation.

LEVA: Using Large Language Models to Enhance Visual Analytics.

Visual analytics supports data analysis tasks within complex domain problems. However, due to the richness of data types, visual designs, and interaction designs, users need to recall and process a significant amount of information when they visually analyze data. These challenges emphasize the need for more intelligent visual analytics methods. Large language models have demonstrated the ability to interpret various forms of textual data, offering the potential to facilitate intelligent support for visual analytics. We propose LEVA, a framework that uses large language models to enhance users' VA workflows at multiple stages: onboarding, exploration, and summarization. To support onboarding, we use large language models to interpret visualization designs and view relationships based on system specifications. For exploration, we use large language models to recommend insights based on the analysis of system status and data to facilitate mixed-initiative exploration. For summarization, we present a selective reporting strategy to retrace analysis history through a stream visualization and generate insight reports with the help of large language models. We demonstrate how LEVA can be integrated into existing visual analytics systems. Two usage scenarios and a user study suggest that LEVA effectively aids users in conducting visual analytics.

Effects of intensive chlorine disinfection on nitrogen and phosphorus removal in WWTPs.

The increased use of disinfection since the pandemic has led to increased effective chlorine concentration in municipal wastewater. Whereas, the specific impacts of active chlorine on nitrogen and phosphorus removal, the mediating communities, and the related metabolic activities in wastewater treatment plants (WWTPs) lack systematic investigation. We systematically analyzed the influences of chlorine disinfection on nitrogen and phosphorus removal activities using activated sludge from five full-scale WWTPs. Results showed that at an active chlorine concentration of 1.0 mg/g-SS, the nitrogen and phosphorus removal systems were not significantly affected. Major effects were observed at 5.0 mg/g-SS, where the nitrogen and phosphorus removal efficiency decreased by 38.9 % and 44.1 %, respectively. At an active chlorine concentration of 10.0 mg/g-SS, the nitrification, denitrification, phosphorus release and uptake activities decreased by 15.1 %, 69.5-95.9 %, 49.6 % and 100 %, respectively. The proportion of dead cells increased by 6.1 folds. Reverse transcriptional quantitative polymerase chain reaction (RT-qPCR) analysis showed remarkable inhibitions on transcriptions of the nitrite oxidoreductase gene (nxrB), the nitrite reductase genes (nirS and nirK), and the nitrite reductase genes (narG). The nitrogen and phosphorus removal activities completely disappeared with an active chlorine concentration of 25.0 mg/g-SS. Results also showed distinct sensitivities of different functional bacteria in the activated sludge. Even different species within the same functional group differ in their susceptibility. This study provides a reference for the understanding of the threshold active chlorine concentration values which may potentially affect biological nitrogen and phosphorus removal in full-scale WWTPs, which are expected to be beneficial for decision-making in WWTPs to counteract the potential impacts of increased active chlorine concentrations in the influent wastewater.

A rat model of adenoid hypertrophy constructed by using ovalbumin and lipopolysaccharides to induce allergy, chronic inflammation, and chronic intermittent hypoxia.

BACKGROUND: Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH. METHODS: An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-ß were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated. RESULTS: Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-ß levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement. CONCLUSION: The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.

Influence of suspended particulate matters on P dynamics and eutrophication in the highly turbid estuary: A case study in Hangzhou Bay, China.

Phosphorus (P) is an essential biogenic element in ecosystems; but excessive or insufficient P in coastal waters caused by human activities has led to serious ecological issues. However, the understanding of the dynamic processes of different P forms in high turbidity estuaries/bays, as well as their impact on eutrophication and coastal algal blooms, is still relatively limited. To address this issue, we analyzed P dynamics and their impact on eutrophication in Hangzhou Bay (HZB), which is typical of eutrophic and turbid bay worldwide. The concentration of particulate P (PTP) was 3-5 times higher than that of dissolved inorganic phosphorus (DIP). Seasonal sediment resuspension led to the accumulation of suspended particulate matter (SPM) and PTP with regional variation, both maintaining DIP concentrations above 1 µmol/L within the bay. Furthermore, 3000 tons of bioavailable P were retained in the fine-grained SPM, with the potential for outward transport, fueling subsequent harmful algal blooms. A comparative analysis of global coastal waters highlighted that different turbidity levels significantly affect P cycling. Therefore, understanding the relationship between SPM and P in highly turbid waters is crucial for effective management of eutrophication.

JCVI: A versatile toolkit for comparative genomics analysis.

The life cycle of genome builds spans interlocking pillars of assembly, annotation, and comparative genomics to drive biological insights. While tools exist to address each pillar separately, there is a growing need for tools to integrate different pillars of a genome project holistically. For example, comparative approaches can provide quality control of assembly or annotation; genome assembly, in turn, can help to identify artifacts that may complicate the interpretation of genome comparisons. The JCVI library is a versatile Python-based library that offers a suite of tools that excel across these pillars. Featuring a modular design, the JCVI library provides high-level utilities for tasks such as format parsing, graphics generation, and manipulation of genome assemblies and annotations. Supporting genomics algorithms like MCscan and ALLMAPS are widely employed in building genome releases, producing publication-ready figures for quality assessment and evolutionary inference. Developed and maintained collaboratively, the JCVI library emphasizes quality and reusability.

Overexpressed nuclear BAG-1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin.

Bcl-2-associated athanogene-1 (BAG-1) is a multifunctional anti-apoptotic protein which regulates an array of cellular processes, including apoptosis, signaling, proliferation, transcription, and cell motility and has been reported to be over-expressed in a number of human malignancies. To investigate the possible involvement of BAG-1 in tumorigenesis of hepatocellular carcinoma (HCC), we performed Western blot analysis in eight paired samples of HCC and adjacent peritumoral tissues and immunohistochemistry in 65 paraffin sections of HCC, which both showed an enhanced expression of nuclear BAG-1 isoform in HCC tissues. Statistical analysis confirmed that overexpression of nuclear BAG-1 in HCC tissues was significantly associated with histological grading (P < 0.001), poor prognosis (P = 0.004), and was found to be an independent prognostic indicator for HCC (P = 0.023). We also noted that BAG-1 was overexpressed in four HCC cell lines compared with a normal hepatocyte cell line, and BAG-1 overexpression increased resistance of HCC cells to doxorubicin, a common chemotherapeutic agent for HCC. Furthermore, we observed that knock down of BAG-1 with siRNA in HepG2 cells increased the chemosensitivity of cells, a process mediated through inhibition of doxorubicin-triggered NF-κB activation; and knock down of BAG-1 suppressed proliferation and cell cycle transition of HepG2 cells. In consequence, our results for the first time indicated that BAG-1 was dysregulated in HCC and suppression of BAG-1 expression which resulted in inhibiting of NF-κB signaling might be developed into a new strategy in HCC therapy.

D-Lactic acid biosynthesis from biomass-derived sugars via Lactobacillus delbrueckii fermentation.

Poly-lactic acid (PLA) derived from renewable resources is considered to be a good substitute for petroleum-based plastics. The number of poly L-lactic acid applications is increased by the introduction of a stereocomplex PLA, which consists of both poly-L and D-lactic acid and has a higher melting temperature. To date, several studies have explored the production of L-lactic acid, but information on biosynthesis of D-lactic acid is limited. Pulp and corn stover are abundant, renewable lignocellulosic materials that can be hydrolyzed to sugars and used in biosynthesis of D-lactic acid. In our study, saccharification of pulp and corn stover was done by cellulase CTec2 and sugars generated from hydrolysis were converted to D-lactic acid by a homofermentative strain, L. delbrueckii, through a sequential hydrolysis and fermentation process (SHF) and a simultaneous saccharification and fermentation process (SSF). 36.3 g L(-1) of D-lactic acid with 99.8 % optical purity was obtained in the batch fermentation of pulp and attained highest yield and productivity of 0.83 g g(-1) and 1.01 g L(-1) h(-1), respectively. Luedeking-Piret model described the mixed growth-associated production of D-lactic acid with a maximum specific growth rate 0.2 h(-1) and product formation rate 0.026 h(-1), obtained for this strain. The efficient synthesis of D-lactic acid having high optical purity and melting point will lead to unique stereocomplex PLA with innovative applications in polymer industry.