Spectral insights: Navigating the frontiers of biomedical and microbiological exploration with Raman spectroscopy.

Raman spectroscopy (RS), a powerful analytical technique, has gained increasing recognition and utility in the fields of biomedical and biological research. Raman spectroscopic analyses find extensive application in the field of medicine and are employed for intricate research endeavors and diagnostic purposes. Consequently, it enjoys broad utilization within the realm of biological research, facilitating the identification of cellular classifications, metabolite profiling within the cellular milieu, and the assessment of pigment constituents within microalgae. This article also explores the multifaceted role of RS in these domains, highlighting its distinct advantages, acknowledging its limitations, and proposing strategies for enhancement.

Female reproductive and hormonal factors and lung cancer mortality among never-smokers: A prospective cohort study of 287 408 Chinese women.

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development.

Effect of Dipyridamole on Membrane Energization and Energy Transfer in Chromatophores of Rba. sphaeroides.

Effect of dipyridamole (DIP) at concentrations up to 1 mM on fluorescent characteristics of light-harvesting complexes LH2 and LH1, as well as on conditions of photosynthetic electron transport chain in the bacterial chromatophores of Rba. sphaeroides was investigated. DIP was found to affect efficiency of energy transfer from the light-harvesting complex LH2 to the LH1-reaction center core complex and to produce the long-wavelength ("red") shift of the absorption band of light-harvesting bacteriochlorophyll molecules in the IR spectral region at 840-900 nm. This shift is associated with the membrane transition to the energized state. It was shown that DIP is able to reduce the photooxidized bacteriochlorophyll of the reaction center, which accelerated electron flow along the electron transport chain, thereby stimulating generation of the transmembrane potential on the chromatophore membrane. The results are important for clarifying possible mechanisms of DIP influence on the activity of membrane-bound functional proteins. In particular, they might be significant for interpreting numerous therapeutic effects of DIP.

Evaluating risk factors for lung cancer among never-smoking individuals using two Australian studies.

PURPOSE: Lung cancer (LC) in never-smoking individuals would rank as Australia's eighth most deadly cancer, yet risk factors remain uncertain. We investigated demographic, lifestyle and health-related exposures for LC among never-smoking Australians. METHODS: Using the prospective 45 and Up Study with 267,153 New South Wales (NSW) residents aged ≥ 45 years at recruitment (2006-2009), we quantified the relationship of 20 potential exposures with LC among cancer-free participants at baseline who self-reported never smoking. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident LC were estimated using Cox regression. The NSW Cancer, Lifestyle and Evaluation of Risk (CLEAR) Study, a case-control study including 10,781 NSW residents aged ≥ 18 years (2006-2014), was used to examine 16 potential LC exposures among cancer-free never-smoking participants. Adjusted odds ratios (OR) and 95% CI of LC were estimated using logistic regression. RESULTS: There were 226 LC cases among 132,354 cancer-free 45 and Up Study participants who reported never smoking, with a median follow-up of 5.41 years. The CLEAR Study had 58 LC cases and 1316 cancer-free controls who had never smoked. Analyses of both datasets showed that Asian-born participants had a higher risk of LC than those born elsewhere: cohort, adjusted HR = 2.83 (95% CI 1.64-4.89) and case-control, adjusted OR = 3.78 (1.19-12.05). No significant association with LC was found for other exposures. CONCLUSION: Our findings support the growing evidence that never-smoking, Asian-born individuals are at higher risk of developing LC than those born elsewhere. Ethnicity could be considered when assessing potential LC risk among never-smoking individuals.

Solid Fuel, Secondhand Smoke, and Lung Cancer Mortality: A Prospective Cohort of 323,794 Chinese Never-Smokers.

Rationale: Household air pollution and secondhand tobacco smoke are known carcinogens for lung cancer, but large-scale estimates of the relationship with lung cancer mortality are lacking. Objectives: Using the large-scale cohort China Kadoorie Biobank, we prospectively investigated associations between these two risk factors and lung cancer death among never-smokers. Methods: The Biobank recruited 512,715 adults aged 30-79 years from 10 regions in China during 2004-2008. Self-reported never-smoking participants were followed up to December 31, 2016, with linkage to mortality data. Total duration of exposure to household air pollution was calculated from self-reported domestic solid fuel use. Exposure to secondhand tobacco smoke was ascertained using exposure at home and/or other places. Hazard ratios and 95% confidence intervals for associations between these two exposures and lung cancer death were estimated using Cox regression, adjusting for key confounders. Measurements and Main Results: There were 979 lung cancer deaths among 323,794 never-smoking participants without a previous cancer diagnosis during 10.2 years of follow-up. There was a log-linear positive association between exposure to household air pollution and lung cancer death, with a 4% increased risk per 5-year increment of exposure (hazard ratio = 1.04; 95% confidence interval = 1.01-1.06; P trend = 0.0034), and participants with 40.1-50.0 years of exposure had the highest risk compared with the never-exposed (hazard ratio = 1.53; 95% confidence interval = 1.13-2.07). The association was largely consistent across various subgroups. No significant association was found between secondhand smoke and lung cancer death. Conclusions: This cohort study provides new prospective evidence suggesting that domestic solid fuel use is associated with lung cancer death among never-smokers.

Evaluating Prognostic Factors for Sex Differences in Lung Cancer Survival: Findings From a Large Australian Cohort.

INTRODUCTION: Women tend to survive a lung cancer diagnosis longer than men; however potential drivers of this sex-related disparity remain largely elusive. We quantified factors related to sex differences in lung cancer survival in a large prospective cohort in Australia. METHODS: Participants in the 45 and Up Study (recruited 2006-2009) diagnosed with incident lung cancer were followed up to December 2015. Prognostic factors were identified from questionnaire data linked with cancer registrations, hospital inpatient records, emergency department records, and reimbursement records for government-subsidized medical services and prescription medicines. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer death for men versus women were estimated using Cox proportional hazard regression in relation to key prognostic factors alone and jointly. RESULTS: A total of 488 women and 642 men were diagnosed with having lung cancer. Women survived significantly longer (median 1.28 versus 0.77 y; HR for men = 1.43, 95% CI: 1.25-1.64, p < 0.0001). The survival disparity remained when each subgroup of major prognostic factors was evaluated separately, including histologic subtype, stage at diagnosis, treatment received, and smoking status. Multivariable analyses revealed that treatment-related factors explained half of the survival difference, followed by lifestyle and tumor characteristics (explaining 28%, 26%, respectively). After adjusting for all major known prognostic factors, the excess risk for men was reduced by more than 80% (HR = 1.06, 95% CI: 0.96-1.18, p = 0.26). CONCLUSIONS: The sex-related lung cancer survival disparity in this Australian cohort was largely accounted for by known prognostic factors, indicating an opportunity to explore sex differences in treatment preferences, options, and access.

Raman Spectroscopy and Its Modifications Applied to Biological and Medical Research.

Nowadays, there is an interest in biomedical and nanobiotechnological studies, such as studies on carotenoids as antioxidants and studies on molecular markers for cardiovascular, endocrine, and oncological diseases. Moreover, interest in industrial production of microalgal biomass for biofuels and bioproducts has stimulated studies on microalgal physiology and mechanisms of synthesis and accumulation of valuable biomolecules in algal cells. Biomolecules such as neutral lipids and carotenoids are being actively explored by the biotechnology community. Raman spectroscopy (RS) has become an important tool for researchers to understand biological processes at the cellular level in medicine and biotechnology. This review provides a brief analysis of existing studies on the application of RS for investigation of biological, medical, analytical, photosynthetic, and algal research, particularly to understand how the technique can be used for lipids, carotenoids, and cellular research. First, the review article shows the main applications of the modified Raman spectroscopy in medicine and biotechnology. Research works in the field of medicine and biotechnology are analysed in terms of showing the common connections of some studies as caretenoids and lipids. Second, this article summarises some of the recent advances in Raman microspectroscopy applications in areas related to microalgal detection. Strategies based on Raman spectroscopy provide potential for biochemical-composition analysis and imaging of living microalgal cells, in situ and in vivo. Finally, current approaches used in the papers presented show the advantages, perspectives, and other essential specifics of the method applied to plants and other species/objects.

Lung cancer risk in never-smokers: An overview of environmental and genetic factors.

Lung cancer is the leading cause of cancer-related mortality globally, accounting for 1.8 million deaths in 2020. While the vast majority are caused by tobacco smoking, 15%-25% of all lung cancer cases occur in lifelong never-smokers. The International Agency for Research on Cancer (IARC) has classified multiple agents with sufficient evidence for lung carcinogenesis in humans, which include tobacco smoking, as well as several environmental exposures such as radon, second-hand tobacco smoke, outdoor air pollution, household combustion of coal and several occupational hazards. However, the IARC evaluation had not been stratified based on smoking status, and notably lung cancer in never-smokers (LCINS) has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. Among several risk factors proposed for the development of LCINS, environmental factors have the most available evidence for their association with LCINS and their roles cannot be overemphasized. Additionally, while initial genetic studies largely focused on lung cancer as a whole, recent studies have also identified genetic risk factors for LCINS. This article presents an overview of several environmental factors associated with LCINS, and some of the emerging evidence for genetic factors associated with LCINS. An increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker's personal risk for lung cancer, but also has important public health implications for the prevention and early detection of the disease. Conclusive evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety, urban design, energy use and particle emissions, and the importance of considering the impacts of second-hand smoke in tobacco control policy.

Effect of thiamethoxam on photosynthetic pigments and primary photosynthetic reactions in two maize genotypes (Zea mays).

Neonicotinoid insecticides are used against the wide range of pests to protect plants. The influence of neonicotinoids on target and non-target insects is well understood. Hence, there are controversial opinions about the effect of neonicotinoids on the plants. We investigated pigments and photosynthetic primary reactions in two maize genotypes (the inbred line zppl 225 and hybrid zp 341) under thiamethoxam (TMX) treatment by root irrigation. It was found that the effect of TMX depended on pesticide application techniques and selection of maize genotype. TMX was added to the soil by root irrigation on the 4th and 8th days after planting, and photosynthetic characteristics monitored on the 10th and 12th days after planting. The primary photochemical reactions in PSII (Fv/Fm) of both maize genotypes were not affected under two variants of TMX treatment during all growing period. The hybrid zp341 was shown to be more susceptible to both TMX treatments, demonstrating a decrease in photosynthetic characteristics (JIP-test parameters) as well as changes in the content of pigments and in the conformation of the carotenoid molecule. Our findings suggest that the combination of fluorescence method and Raman spectroscopy is a perspective tool for monitoring plant state under pesticide application.

Effect of Dinitrosyl Iron Complex on Albumin Conformation.

Binding of dinitrosyl iron complex (DNIC) to albumin was studied using time-resolved fluorescence (TRF) and electron spin resonance (ESR) spectroscopy. It was found that the fluorescence lifetime of bovine serum albumin (BSA) and human serum albumin (HSA) decreases with binding and depends on DNIC concentration. The observed biexponential pattern of the BSA tryptophan (Trp) fluorescence decay is explained by the presence of two tryptophan residues in the protein molecule. We believe that DNIC forms stable complexes with the cysteine (Cys34) residue in the domain I of albumin. It was shown that the lifetime of albumin tryptophan fluorescence decreased during co-incubation of BSA with DNICs and glutathione. Effects of DNIC on the binding of specific spin-labeled fatty acids with albumin in human blood plasma were studied in vitro. The presence of DNIC in blood plasma does not change conformation of albumin domains II and III. We suggest that the most possible interaction between DNICs and albumin is the formation of a complex; and nitrosylation of the cysteine residue in the albumin domain I occurs without the changes in albumin conformation.

Systematic review and meta-analysis of residential radon and lung cancer in never-smokers.

BACKGROUND: Globally, radon is the leading risk factor for lung cancer in never-smokers (LCINS). In this study, we systematically reviewed and meta-analysed the evidence of the risk of LCINS associated with residential radon exposure. METHODS: Medline and Embase databases were searched using predefined inclusion and exclusion criteria to identify relevant studies published from 1 January 1990 to 5 March 2020 focused on never-smokers. We identified four pooled collaborative studies (incorporating data from 24 case-control studies), one case-control study and one cohort study for systematic review. Meta-analysis was performed on the results of the four pooled studies due to different measures of effect and outcome reported in the cohort study and insufficient information reported for the case-control study. In a post hoc analysis, the corresponding risk for ever-smokers was also examined. RESULTS: Risk estimates of lung cancer from residential radon exposure were pooled in the meta-analysis for 2341 never-smoker cases, 8967 never-smoker controls, 9937 ever-smoker cases and 12 463 ever-smoker controls. Adjusted excess relative risks (aERRs) per 100 Bq·m-3 of radon level were 0.15 (95% CI 0.06-0.25) for never-smokers and 0.09 (95% CI 0.03-0.16) for ever-smokers, and the difference between them was statistically insignificant (p=0.32). The aERR per 100 Bq·m-3was higher for men (0.46; 95% CI 0.15-0.76) than for women (0.09; 95% CI -0.02-0.20) among never-smokers (p=0.027). CONCLUSION: This study provided quantified risk estimates for lung cancer from residential radon exposure among both never-smokers and ever-smokers. Among never-smokers in radon-prone areas, men were at higher risk of lung cancer than women.

Effect of the NBD-group position on interaction of fluorescently-labeled cholesterol analogues with human steroidogenic acute regulatory protein STARD1.

Steroidogenic acute regulatory protein (StAR, STARD1) is a key factor of intracellular cholesterol transfer to mitochondria, necessary for adrenal and gonadal steroidogenesis, and is an archetypal member of the START protein family. Despite the common overall structural fold, START members differ in their binding selectivity toward various lipid ligands, but the lack of direct structural information hinders complete understanding of the binding process and cholesterol orientation in the STARD1 complex in particular. Cholesterol binding has been widely studied by commercially available fluorescent steroids, but the effect of the fluorescent group position on binding remained underexplored. Here, we dissect STARD1 interaction with cholesterol-like steroids bearing 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group in different positions, namely, with 22-NBD-cholesterol (22NC), 25-NBD-cholesterol (25NC), 20-((NBDamino)-pregn-5-en-3-ol (20NP) and 3-(NBDamino)-cholestane (3NC). While being able to stoichiometrically bind 22NC and 20NP with high fluorescence yield and quantitative exhaustion of fluorescence of some protein tryptophans, STARD1 binds 25NC and 3NC with much lower affinity and poor fluorescence response. In contrast to 3NC, binding of 20NP leads to STARD1 stabilization and substantially increases the NBD fluorescence lifetime. Remarkably, in terms of fluorescence response, 20NP slightly outperforms commonly used 22NC and can thus be used for screening of various potential ligands by a competition mechanism in the future.

Study of myelin structure changes during the nerve fibers demyelination.

Raman, NMR and EPR spectroscopy and electrophysiology methods were used to investigate the excitability and the packaging of myelin lipid layers and its viscosity during nerve exposure to pronase E. It was established that during exposure of nerve to pronase E the action potential (AP) conduction velocity and the Schwann cell (SC) (or myelin) water ordering increases, but the nerve myelin refractive index and internode incisions numbers decrease. This effect included two periods-short- and long-time period, probably, because the first one depends on SC protein changes and the second one-on the nerve fiber internode demyelination. It was concluded that high electrical resistance of myelin, which is important for a series of AP conduction velocity, not only depends on nerve fiber diameter and the myelin lipid composition, but also on the regularity of myelin lipid fatty acids and myelin lipid layer packing during the axoglial interaction.

Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors.

In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh) regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC) acetylcholine receptors (AChRs) and the axon excitation (different intervals between action potentials (APs)). Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the "axon-SC" interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+-influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization.

Bariatric surgery: An HIV-positive patient's successful journey.

Bariatric surgery is becoming increasingly common in the UK. Little has been done to evaluate its place in HIV-positive patients. Here, we discuss a successful case and the complexities surrounding highly active antiretroviral therapy.

Immunisation against plague by transcutaneous and intradermal application of subunit antigens.

We have investigated immunological responses in BALB/c mice following transcutaneous (TC) delivery of fraction 1 (F1) and V subunits from Yersinia pestis in conjunction with an enterotoxin-derived adjuvant (cholera toxin, CT). It was found that two or more TC applications of F1 and V subunits (admixed with cholera toxin) served to elicit significant levels of anti-F1 and V antibodies in the serum of immunised mice. IL-6 secretion from cultured splenocytes derived from immunised mice indicated that a single TC application of F1 and V subunits (admixed with cholera toxin) conferred a cell-mediated response. As compared with intranasal or direct intradermal injection of F1 and V, the numbers of F1/V-specific antibody-forming cells in the spleens of animals immunised by TC application of F1 and V (admixed with CT) was relatively low. It was noted that TC application of F1 and V admixed with CT was very effective for priming responses that were boosted by intranasal or intradermal routes. Similarly, it was found that TC application of F1 and V admixed with CT could be used to efficiently boost pre-existing responses engendered by intradermal injection or intranasal instillation of F1 and V. In order to assess if TC application of F1 and V admixed with CT could protect experimental animals from plague, immunised mice were injected with a virulent strain of Y. pestis. It was found that two TC applications of F1 and V admixed with CT conferred only limited protection against 10(2) MLDs. However, three TC applications of F1 and V admixed with CT conferred solid protection against 10(2) MLDs. Hence we have shown, for the first time, that TC application of F1 and V admixed with CT can protect animals against challenge with a virulent strain of plague causing bacteria. These data suggest that transcutaneous immunisation may be a simple and non-invasive method for immunising individuals against plague.

An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitis virus vaccine.

The live attenuated vaccine strain of Venezuelan equine encephalitis virus (VEEV), TC-83, protects mice against challenge (subcutaneous and aerosol) with virulent VEEV but is not suitable for widescale human use. Elucidation of the immune response profile of protected mice should assist in the development of an improved vaccine. We determined the optimum dose of TC-83 required to consistently protect Balb/c mice from airborne challenge with the virulent Trinidad Donkey strain of VEEV and studied the development of humoral and cellular immune responses in protected mice between 6 h and 21 days post-vaccination. The most dramatic immune responses occurred in draining lymph nodes 24 h following vaccination with increased levels of activated B cells and T cells of both CD4(+) and CD8(+) subtypes. Activated monocyte/macrophages and natural killer cells were also seen between 6 h and 7 days post-vaccination. Serum contained detectable VEEV-specific IgG on day 5 post-vaccination with titres continuing to rise on days 7, 14 and 21. Isotypes of IgG measured on days 7 and 21 were predominantly of the IgG2a subclass, indicating that the immune response was Th1-mediated. Cytokine mRNA was quantified by RT-PCR and revealed production of the Th1 cytokine IFN-gamma and the inflammatory cytokine TNF-alpha, whereas the Th2 cytokine IL4 was not detected above control levels at any of the time points studied. This data describes key cellular immune responses at early times post-vaccination and is consistent with previous data demonstrating protection against aerosol challenge with VEEV in the absence of detectable levels of specific IgG or IgA antibody.

The optimisation of a murine TNF-alpha ELISA and the application of the method to other murine cytokines.

Cytokines occur in biological systems at low levels of concentration, therefore assays developed to measure them must be very sensitive. Enzyme linked immunosorbent assays (ELISA's) developed using manufacturers recommended end points can detect cytokines to picogram levels but the lower parts of their standard curves can be unreliable. In this study the relative merits of different substrate systems - 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2 forms of tetramethyl benzidine (TMB), were investigated with regard to assay sensitivity. Further, a signal amplification method involving biotinylated tyramine has been used to increase the absorbance signal and thus the assay sensitivity and to achieve a sigmoidal standard curve. The amplified assay approach has been applied successfully to achieve more sensitive detection of TNF-alpha and improve the sensitivity of assays for a wide range of other cytokines. The optimised amplification method is the same for all the cytokine ELISA's performed in this work and this enables them to be performed