Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus.

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.

Integrating single-cell and multi-omic approaches reveals Euphorbiae Humifusae Herba-dependent mitochondrial dysfunction in non-small-cell lung cancer.

Euphorbiae Humifusae Herba (EHH) is a pivotal therapeutic agent with diverse pharmacological effects. However, a substantial gap exists in understanding its pharmacological properties and anti-tumour mechanisms. This study aimed to address this gap by exploring EHH's pharmacological properties, identifying NSCLC therapy-associated protein targets, and elucidating how EHH induces mitochondrial disruption in NSCLC cells, offering insights into novel NSCLC treatment strategies. String database was utilized to explore protein-protein interactions. Subsequently, single-cell analysis and multi-omics further unveiled the impact of EHH-targeted genes on the immune microenvironment of NSCLC, as well as their influence on immunotherapeutic responses. Finally, both in vivo and in vitro experiments elucidated the anti-tumour mechanisms of EHH, specifically through the assessment of mitochondrial ROS levels and alterations in mitochondrial membrane potential. EHH exerts its influence through engagement with a cluster of 10 genes, including the apoptotic gene CASP3. This regulatory impact on the immune milieu within NSCLC holds promise as an indicator for predicting responses to immunotherapy. Besides, EHH demonstrated the capability to induce mitochondrial ROS generation and perturbations in mitochondrial membrane potential in NSCLC cells, ultimately leading to mitochondrial dysfunction and consequent apoptosis of tumour cells. EHH induces mitochondrial disruption in NSCLC cells, leading to cell apoptosis to inhibit the progress of NSCLC.

Associations between plasma metal/metalloid mixtures and the risk of central obesity: A prospective cohort study of Chinese adults.

Central obesity has increased rapidly over the past decade and posed a substantial disease burden worldwide. Exposure to metals/metalloids has been acknowledged to be involved in the development of central obesity through regulation of cortisol, insulin resistance, and glucocorticoid receptor reduction. Despite the importance, it is lack of prospective study which comprehensively evaluate the relations between multiple metals exposure and central obesity. We explored the prospective associations of plasma metal concentrations with central obesity in a prospective study of the Dongfeng-Tongji cohort. The present study included 2127 participants with a 6.87-year mean follow-up duration. We measured 23 plasma metal/metalloid concentrations at baseline. The associations between metals and incident central obesity were examined utilizing the Cox proportional hazard regression in single and multiple metals models. Additionally, we applied elastic net (ENET), Bayesian kernel machine regression (BKMR), plasma metal score (PMS), and quantile-based g-computation (Qgcomp) models to explore the joint associations of metal mixtures with central obesity. After adjusting potential confounders, we found significant associations of plasma manganese (Mn) and thallium (Tl) concentrations with a higher risk of central obesity, whereas plasma rubidium (Rb) concentration was associated with a lower risk of central obesity both in single and multiple metals models (all FDR <0.05). The ENET and Qqcomp models verified similar metals (Mn, Rb, and Tl) as important predictors for central obesity. The results of both BKMR model and PMS suggested cumulative exposure to metal mixtures was associated with a higher risk of central obesity. Our findings suggested that co-exposure to metals was associated with a higher risk of central obesity. This study expands our knowledge that the management of metals/metalloids exposure may be beneficial for the prevention of new-onset central obesity, which may subsequently alleviate the disease burden of late-life health outcomes.

MiR-2110 induced by chemically synthesized cinobufagin functions as a tumor-metastatic suppressor via targeting FGFR1 to reduce PTEN ubiquitination degradation in nasopharyngeal carcinoma.

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.

Environmental justice of Texas recreational water quality - The disproportionate E. coli levels and trends.

The presence of pathogens is one of the leading causes of stream water quality impairment in the US. Escherichia coli (E. coli) is a fecal pathogen indicator and also signals the presence of more pathogenic microbes. Although it is reported that Black, Indigenous, and communities of color suffer more from E. coli contamination, there is a lack of investigation of the potential inequality of E. coli contamination in recreational waterbodies, particularly regarding whether this inequality persists over the long term. Using E. coli monitoring data from 1,424 stations from 2001 to 2021 in Texas, we tested the research hypotheses of racial and economic inequalities in E. coli levels and trends with quantile regression and logistic regression approaches. We found that economic disparities had a more significant relationship with E. coli contamination in Texas recreational waterbodies than racial disparities after controlling for building age, land covers, imperviousness, and precipitation. The economic disparities in E. coli contamination were more prevalent after 2010 and in extreme E. coli levels. In addition, implementing watershed protection plans could mitigate the economic disparities associated with the rising trend of E. coli levels between 2001 and 2021. Findings from this research underscore clean surface water deprivation from underserved communities and call for inclusive watershed management strategies to address the water quality injustice.

Effect of Potentilla anserina L. powder on gel properties and volatile flavor characteristics of silver carp surimi.

BACKGROUND: Potentilla anserina L. is rich in various nutrients, active ingredients and unique flavor, comprising a natural nutrition and health food. However, its application in aquatic food has been rarely reported. Therefore, the effects of Potentilla anserina L. powder (PAP) on gel properties and volatile flavor profile of silver carp surimi were investigated. RESULTS: The gel strength and water-holding capacity of the surimi gels were significantly improved (P < 0.05), and the whiteness and cooking loss of all the samples decreased slightly with the increase in PAP content. The addition of PAP shortened the relaxation time (T2) of the surimi gels and converted some of the free water into immobile or bound water, which resulted in a better immobilization of water in the surimi. Scanning electron microscopy images demonstrated that the network of surimi gels with PAP added was denser and had a smoother surface compared to the control. Volatile components (VCs) analysis showed that 33 VCs were identified in the surimi gel samples with different additions of PAP, among which aldehydes, alcohols and esters were the major VCs, accounting for more than 50% of the VCs in the surimi gels. PAP addition reduced the fishy and rancid flavor compounds in surimi gels, such as 1-propanol, 1-octen-3-ol, etc., and promoted the production of aldehydes, alcohols, esters and other flavor substances. CONCLUSION: These results of the present study provide theoretical support for the investigation and development of new nutrient-health-flavored surimi products. © 2024 Society of Chemical Industry.

The OsMAPK5-OsWRKY72 module negatively regulates grain length and grain weight in rice.

Grain size and grain weight are important determinants for grain yield. In this study, we identify a novel OsMAPK5-OsWRKY72 module that negatively regulates grain length and grain weight in rice. We found that loss-of-function of OsMAPK5 leads to larger cell size of the rice spikelet hulls and a significant increase in both grain length and grain weight in an indica variety Minghui 86 (MH86). OsMAPK5 interacts with OsMAPKK3/4/5 and OsWRKY72 and phosphorylates OsWRKY72 at T86 and S88. Similar to the osmapk5 MH86 mutants, the oswrky72 knockout MH86 mutants exhibited larger size of spikelet hull cells and increased grain length and grain weight, whereas the OsWRKY72-overexpression MH86 plants showed opposite phenotypes. OsWRKY72 targets the W-box motifs in the promoter of OsARF6, an auxin response factor involved in auxin signaling. Dual-luciferase reporter assays demonstrated that OsWRKY72 activates OsARF6 expression. The activation effect of the phosphorylation-mimicking OsWRKY72T86D/S88D on OsARF6 expression was significantly enhanced, whereas the effects of the OsWRKY72 phosphorylation-null mutants were significantly reduced. In addition, auxin levels in young panicles of the osmapk5 and oswrky72 mutants were significantly higher than that in the wild-type MH86. Collectively, our study uncovered novel connections of the OsMAPKK3/4/5-OsMAPK5-mediated MAPK signaling, OsWRKY72-mediated transcription regulation, and OsARF6-mediated auxin signaling pathways in regulating grain length and grain weight in an indica-type rice, providing promising targets for molecular breeding of rice varieties with high yield and quality.

Integrating Systems and Synthetic Biology to Understand and Engineer Microbiomes.

Microbiomes are complex and ubiquitous networks of microorganisms whose seemingly limitless chemical transformations could be harnessed to benefit agriculture, medicine, and biotechnology. The spatial and temporal changes in microbiome composition and function are influenced by a multitude of molecular and ecological factors. This complexity yields both versatility and challenges in designing synthetic microbiomes and perturbing natural microbiomes in controlled, predictable ways. In this review, we describe factors that give rise to emergent spatial and temporal microbiome properties and the meta-omics and computational modeling tools that can be used to understand microbiomes at the cellular and system levels. We also describe strategies for designing and engineering microbiomes to enhance or build novel functions. Throughout the review, we discuss key knowledge and technology gaps for elucidating the networks and deciphering key control points for microbiome engineering, and highlight examples where multiple omics and modeling approaches can be integrated to address these gaps.

Hemin functionalized hybrid aerogel-enabled electrochemical chip for real-time analysis of H2O2.

Herein, a novel hemin functionalized hybrid aerogel (He@GMA) is synthesized and applied to an electrochemical chip for real-time analysis of hydrogen peroxide (H2O2). The He@GMA shows a typical three-dimensional morphology and excellent peroxidase-like catalytic performance. The He@GMA-enabled electrochemical chip presents satisfactory performance for H2O2 sensing with a low limit of detection (0.96 µM). Besides, the chip platform shows some advantages of less sample consumption and easier detection operation.

Multiplexed evaluation of immunity against SARS-CoV-2 variants using surface enhanced fluorescence from a nanostructured plasmonic chip.

Generated by the immune system post-infection or through vaccination, the effectiveness of antibodies against emerging SARS-CoV-2 variants is crucial for protecting individuals from the COVID-19 pandemic. Herein, a platform for the multiplexed evaluation of SARS-CoV-2 neutralizing antibodies against various variants was designed on the basis of near-infrared (NIR) surface enhanced fluorescence by nano-plasmonic gold chip (pGOLD). Antibody level across variants (Wild-type, Alpha, Beta, Delta, Omicron) was confirmed by the sera from recovered-individuals who were unvaccinated and had infected with Wild-type, Delta, Omicron variants. However, the neutralizing activity against Omicron variant was markedly decreased for individuals infected by Wild-type (~ 5.6-fold) and Delta variant (~ 19.1-fold). To the opposite, neutralizing antibody from individuals recovered from Omicron variant infection showed weak binding strength against non-Omicron variants. Antibody evolution over time was studied with individuals 196-530 days post Wild-type infection. Decreasing IgG antibody titer accompanied by increasing IgG binding avidity with elongated post-infection period were observed for the sera from Wild-type recovered-individuals with different post-infection times, suggesting that after the primary infection, a great number of antibodies were generated and then gradually decreased, while the antibody matured over time. By comparing the IgG level of individuals vaccinated for 27-51 days with individual post-infection, we found that ca. 1 month after two doses of vaccination, the antibody level was comparable to that of 500 days post-infection, and vaccination could enhance IgG avidity more efficiently. This work demonstrated a platform for the multiplexed, high-throughput and rapid screening of acquired immunity against SARS-CoV-2 variants, providing a new approach for the analysis of vaccine effectiveness, immunity against emerging variants, and related serological study.

Identification of Bi-2-naphthol and Its Phosphate Derivatives Complexed with Cyclodextrin and Metal Ions Using Trapped Ion Mobility Spectrometry.

The separation of chiral enantiomers has gained increasing importance in many research fields, becoming a major research hotspot. 1,1'-Bi (2-naphthol) (BINOL) and 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP) are referred to as atropisomer chiral molecules, which are essential chiral catalysts and intermediates in several reactions. In this work, BINOL and BNP atropisomers are separated and identified using trapped ion mobility spectrometry (TIMS) to monitor the different mobilities of their derivative complexes. The latter are obtained by the simple mixing of BINOL/BNP, cyclodextrin (CD), and the metal ions through noncovalent interactions. The results indicate that the enantiomer complexes of BINOL/BNP can be separated with a certain specificity, showing that R-, S-BINOL can be separated by the ternary complexes of [BINOL+γ-CD + Rb]+, [BINOL+γ-CD + Cu-H]+, and [BINOL+ß-CD + Cu-H]+ based on the difference in their mobility; similarly, the R-, S-BNP enantiomer can be isolated by the formed ternary complexes of [BNP+α-CD + Ba-H]+, [BNP+ß-CD + Co-H]+, [BNP+ß-CD + Ca-H]+, [BNP+ß-CD + Cu-H]+, [BNP+ß-CD + Fe-H]+, [BNP+ß-CD + Li]+, and [BNP+ß-CD + Sr-H]+. Furthermore, the peak separation rate (Rp-p) of the complexes was calculated, with the Rp-p of the three enantiomers of BINOL being 1.130 and the Rp-p of the seven complexes of BNP reaching 2.089. At last, the different survival yields for the collision energies were found for the enantiomer complexes, revealing the rigid structural differences in the stereospecificity of the enantiomer complexes that result in the separation by the TIMS. Additionally, due to the advantages of simple operation, fast speed, and high sensitivity and because chemical derivatization and chromatographic separation are not required, the developed method can provide a promising and powerful strategy for the separation and identification of binaphthyl derivatives or even other enantiomers of the reaction intermediates.

VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer.

The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) -induced CRC mice models and nicotine-treated CRC cells via the PI3K/AKT/c-Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and the downstream cell cycle or EMT-related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c-Jun-mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c-Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B-modulating signal in VPS33B-overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and thus suppress the malignant phenotype of CRC.

Vertically Aligned Gold Nanowires as Stretchable and Wearable Epidermal Ion-Selective Electrode for Noninvasive Multiplexed Sweat Analysis.

The noninvasive continuous analysis of human sweat is of great significance for improved healthcare diagnostics and treatment in the future, for which a wearable potentiometry-based ion-selective electrode (ISE) has attracted increasing attention, particularly involving ion detection. Note that traditional solid-state ISE electrodes are rigid ion-to-electron transducers that are not conformal to soft human skin and cannot function under stretched states. Here, we demonstrated that vertically aligned mushroom-like gold nanowires (v-AuNW) could serve as stretchable and wearable ion-to-electron transducers for multiplexed, in situ potentiometric analysis of pH, Na+, and K+ in sweat. By modifying v-AuNW electrodes with polyaniline, Na ionophore X, and a valinomycin-based selective membrane, we could specifically detect pH, Na+, and K+, respectively, with high selectivity, reproducibility, and stability. Importantly, the electrochemical performance could be maintained even under 30% strain and during stretch-release cycles without the need of extrinsic structural design. Furthermore, our stretchable v-AuNW ISEs could be seamlessly integrated with a flexible printed circuit board, enabling wireless on-body detection of pH, Na+, and K+ with fast response and negligible cross-talk, indicating considerable promise for noninvasive wearable sweat analysis.

Associations of plasma metal concentrations with the decline in kidney function: A longitudinal study of Chinese adults.

Metals are widespread pollutants in the environment which have been reported to be associated with kidney dysfunction in many existing epidemiological studies. However, most of the studies are cross-sectional design and mainly focus on several toxic metals including arsenic, lead and cadmium. Therefore, we conducted this prospective study within the Dongfeng-Tongji cohort to evaluate the associations of plasma multiple metals with the decline in kidney function among Chinese middle-aged and elderly. In total, 1434 participants free of chronic diseases at baseline were included in analysis. We measured baseline plasma concentrations of 23 metals and calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on serum creatinine, age, sex and ethnicity. Bonferroni correction was used for multiple testing to reduce the probability of a type I error. Principal component analysis was conducted to evaluate the combined effect of multiple metal co-exposure. Most of the plasma metal concentrations were within the literature reported reference values, whereas the concentration of lead and nickel exceeded the guideline value. We found that plasma concentrations of aluminum, arsenic, barium, lead, molybdenum, rubidium, strontium, vanadium and zinc were significantly associated with the decline in kidney function measured by annual eGFR decline, rapid renal function decline (defined as an annual decline in eGFR ≥ 5 mL/min/1.73 m2) or incident eGFR < 60 mL/min/1.73 m2, with the adjusted beta coefficients (95% CI) for annual eGFR decline 0.50 (0.30, 0.69), 0.98 (0.74, 1.23), 0.56 (0.32, 0.79), 0.21 (0.03, 0.39), 0.35 (0.16, 0.54), 0.94 (0.71, 1.17), 0.37 (0.15, 0.60), 0.78 (0.54, 1.02), and 0.74 (0.57, 0.91), respectively. The metals exposures were linked with increased risks of impaired kidney function. Associations of principal components representing these metals with the decline in kidney function were significant and suggest a possible additional health risk by co-exposure. Participants engaged in manufacturing had higher plasma levels of several metals compared with those who had been involved in management- or administration-related work. Our findings suggest that exposure to multiple metals contribute to the decline in kidney function among the middle-aged and elderly. Co-exposure to multiple metals may have synergetic effect on the kidney function. Further studies are warranted to confirm our findings and clarify the potential mechanisms.

Circulating Multiple Metals and Incident Stroke in Chinese Adults.

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.

The effects of HSP27 against UVB-induced photoaging in rat skin.

Skin photoaging refers to the phenomenon of skin aging or accelerated aging as a result of long-term UV exposure. Ultraviolet radiation can lead to DNA damage, cell apoptosis, cell growth inhibition and carcinogenic effects. Evidence suggests that hsp27 can protect cells from apoptosis induced by various stimuli in vivo and in vitro. However, modulation in hsp27 expression toward skin protection against UVB treatment has not been investigated clearly. In this study, we aimed to investigate the effects of hsp27 against UVB-induced photoaging in rat skin and to explore the underlying mechanisms. In the present study, we identified that the level of hsp27 increased after UVB irradiation induced chronic photoaging rat model. In order to investigate the function of hsp27 in UVB-induced skin photoaging, we used adeno-associated virus (AAV) to specificity reduce the expression of hsp27 in rat skin. In contrast to UVB group, we found that collagen fibers were disorganized and elastic fibers were thickened and twisted in UVB-AAV group. In the UVB-AAV group, reduced hsp27 enhanced the oxidative stress. Aging markers (SA-ß-Gal staining and the protein levels of p16, p53, p21) were significantly changed in the hsp27 decreased group. However, in hsp27 deletion group, the expression of antiapoptotic factor bcl-2 was decreased, while the apoptosis factor bax was increased after UVB irradiation. These findings suggested that hsp27 was involved in oxidative stress, aging and apoptosis of skin after UV exposure. Management the expression of hsp27 can be used as a potential intervention method to alleviate UVB-induced skin damage.

Machine learning based temperature prediction of poly(N-isopropylacrylamide)-capped plasmonic nanoparticle solutions.

The temperature-dependent optical properties of gold nanoparticles that are capped with the thermo-sensitive polymer: 'poly(N-isopropylacrylamide)' (PNIPAM), have been studied extensively for several years. Also, their suitability to function as nanoscopic thermometers for bio-sensing applications has been suggested numerous times. In an attempt to establish this, many have studied the temperature-dependent optical resonance characteristics of these particles; however, developing a simple mathematical relationship between the optical measurements and the solution temperature remains an open challenge. In this paper, we attempt to systematically address this problem using machine learning techniques to quickly and accurately predict the solution-temperature, based on spectroscopic data. Our emphasis is on establishing a simple and practically useful solution to this problem. Our dataset comprises spectroscopic absorption data from both nanorods and nanobipyramids capped with PNIPAM, measured at discretely varied and pre-set temperature states. Specific regions of the spectroscopic data are selected as features for prediction using random forest (RF), gradient boosting (GB) and adaptive boosting (AB) regression techniques. Our prediction results indicate that RF and GB techniques can be used successfully to predict solution temperatures instantly to within 1 °C of accuracy.

miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance.

This study aimed to identify mechanisms by which microRNA 296-3p (miR-296-3p) functions as a tumor suppressor to restrain nasopharyngeal carcinoma (NPC) cell growth, metastasis, and chemoresistance. Mechanistic studies revealed that miR-296-3p negatively regulated by nicotine directly targets the oncogenic protein mitogen-activated protein kinase-activated protein kinase-2 (Mapkapk2) (MK2). Suppression of MK2 downregulated Ras/Braf/Erk/Mek/c-Myc and phosphoinositide-3-kinase (PI3K)/Akt/c-Myc signaling and promoted cytoplasmic translocation of c-Myc, which activated miR-296-3p expression by a feedback loop. This ultimately inhibited cell cycle progression, epithelial-to-mesenchymal transition (EMT), and chemoresistance of NPC. In addition, nicotine as a key component of tobacco was observed to suppress miR-296-3p and thus elevate MK2 expression by inducing PI3K/Akt/c-Myc signaling. In clinical samples, reduced miR-296-3p as an unfavorable factor was inversely correlated with MK2 and c-Myc expression. These results reveal a novel mechanism by which miR-296-3p negatively regulated by nicotine directly targets MK2-induced Ras/Braf/Erk/Mek/c-Myc or PI3K/AKT/c-Myc signaling to stimulate its own expression and suppress NPC cell proliferation and metastasis. miR-296-3p may thus serve as a therapeutic target to reverse chemotherapy resistance of NPC.

Interference of Hsp27 Results in Apoptosis Induced by Photodamage via Regulation of Subcellular Localization of p21 in Immortalized Human Keratinocytes.

BACKGROUND Owing to the increased incidence of photodermatosis caused by ultraviolet light in recent years, it is necessary to clarify the mechanisms potential photodamage to the skin and reveal possible therapeutic targets. Heat shock protein 27 (Hsp27) is well known for suppressing apoptosis. The aim of present study was to elucidate possible photoprotective mechanism between Hsp27 and p21 on ultraviolet B (UVB)-induced photodamage. MATERIAL AND METHODS The Hsp27 gene was interfered to assess the expression of its downstream effectors, cell apoptosis, and cell proliferation ability. The cell apoptosis was tested using flow cytometry method. The cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8) assay. The expression of protein was tested using western-blotting method. The expression of mRNA was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The subcellular localization was elucidated using immunofluorescence. RESULTS Hsp27 knockdown decreased cell viability and increased the incidence of UVB-induced apoptosis. Compared with control group, activation of phosphorylated-Akt (p-Akt)-dependent pathway resulted in the nuclear accumulation of p21 and suppression of cell proliferation, while promoting apoptosis in Hsp27 knockdown group. In addition, Hsp27 knockdown increased p53 expression and the Bax: Bcl-2 ratio, which further accelerated the apoptotic process. CONCLUSIONS These findings complemented the mechanism of skin photodamage and demonstrated the photoprotective mechanisms of Hsp27 in HaCaT cells, which might implicate a potential therapeutic target of photodamage and photodermatosis.