Genome-wide comparative analyses highlights selection signatures underlying saline adaptation in Chilika buffalo.

Chilika, a native buffalo breed of the Eastern coast of India, is mainly distributed around the Chilika brackish water lake connected with the Bay of Bengal Sea. This breed possesses a unique ability to delve deep into the salty water of the lake and stay there to feed on local vegetation of saline nature. Adaptation to salinity is a genetic phenomenon, however, the genetic basis underlying the salinity tolerance is still limited in animals specifically in livestock. The present study explores the genetic evolution that unveils the Chilika buffalo's adaptation to the harsh saline habitat (water and food system). For this study, whole genome resequencing data on 18 Chilika buffalo and for comparison 10 Murrah buffalo of normal habitat were generated. For identification of selection sweeps, intrapopulation and interpopulation statistics were employed. A total of 709, 309, 468, and 354 genes were detected having selection sweeps in Chilika buffalo using the nucleotide diversity (θπ), Tajima's D, nucleotide diversity ratio (θπ-ratio), and FST methods, respectively. Further analysis revealed a total of 23 genes including EXOC6B, VPS8, LYPD1, VPS35, CAMKMT, NCKAP5, COMMD1, MYLK3, B3GNT2 were found to be common by all the methods. Furthermore, functional annotation study of identified genes provided pathways such as MAPK signaling, renin secretion, endocytosis, oxytocin signaling pathway, etc. Gene network analysis enlists hub genes, provide insights into their interactions with each other. In conclusion, this study has highlighted the genetic basis underlying the local adaptive function of Chilika buffalo under saline environment.

Whole genome resequencing revealed genomic variants and functional pathways related to adaptation in Indian yak populations.

The present study aims to identify genomic variants through a whole genome sequencing (WGS) approach and uncover biological pathways associated with adaptation and fitness in Indian yak populations. A total of 30 samples (10 from each population) were included from Arunachali, Himachali and Ladakhi yak populations. WGS analysis revealed a total of 32171644, 27260825, and 32632460 SNPs and 4865254, 4429941, and 4847513 Indels in the Arunachali, Himachali, and Ladakhi yaks, respectively. Genes such as RYR2, SYNE2, BOLA, HF1, and the novel transcript ENSBGRG00000011079 were found to have the maximum number of high impact variants in all three yak populations, and might play a major role in local adaptation. Functional enrichment analysis of genes harboring high impact SNPs revealed overrepresented pathways related to response to stress, immune system regulation, and high-altitude adaptation. This study provides comprehensive information about genomic variants and their annotation in Indian yak populations, thus would serve as a data resource for researchers working on the yaks. Furthermore, it could be well exploited for better yak conservation strategies by estimating population genetics parameters viz., effective population size, inbreeding, and observed and expected heterozygosity.

Comparative analysis of various methods for estimating expected genetic gain of production and reproduction traits in Murrah buffaloes.

The present study was conducted to assess the expected genetic gain for first lactation production and reproduction traits in Murrah buffaloes, in addition to optimization of progenies/sire. Data for period 1971-2020 were used from National Dairy Research Institute. Performance traits considered were 305 days milk yield (305DMY), average daily milk yield (ADMY), peak yield (PY), lactation length (LL), calving to first insemination interval (CFI), days open (DO), and calving interval (CI). Expected ΔG was estimated and compared by three different methods; method I involved heritability and selection differential; method II involved selection intensity, phenotypic standard deviation, and heritability; method III involved estimation of ΔG through four paths of inheritance. Initially, eleven progenies/sire were utilized for assessing expected ΔG by method III, and expected ΔG was found as 34.33, 0.12, 0.12 kg, 2.63, 1.51, 2.74, and 2.80 days/year for 305DMY, ADMY, PY, LL, CFI, DO, and CI, respectively. Additionally, there was a significant increase in expected ΔG on increasing progenies/sire from 6 to 11 while subsequent increase upto 16 had little effect on expected ΔG. These findings will be helpful in formulating breeding strategies worldwide in small buffalo herds to obtain sustainable ΔG in production and reproduction traits.

Comparative gene expression profile in circulating PBMCs of Bos indicus and crossbred cattle to understand disease tolerance mechanism.

The present investigation was performed to compare the global gene expression profile in peripheral blood mononuclear cells (PBMCs) of Bos indicus and crossbred (Bos taurus × B. indicus) cattle. Previously, several studies revealed the disease tolerance potential of B. indicus cattle but underlying genetic mechanism is still not fully explored. The PBMCs model was used for this investigation as it plays crucial role in the immune system regulation. Transcriptomic analysis revealed total 6767 significantly differentially expressed transcripts (fold change (absolute) >2.0, p < .05). In addition, 4149 transcripts were upregulated, 2618 transcripts were downregulated and fold change (absolute) of differentially expressed transcript varied from -223.32 to 213.63. Functional annotation analysis of differentially expressed genes confirmed their role in various molecular pathways viz. innate immune response, antigen processing and presentation, MHC protein complex, defense response to bacterium, regulation of immune response, positive regulation of JAK-STAT cascade, cytoskeletal protein binding, etc. Protein-protein interaction network analysis provided understanding of inter-relationship of immune genes with differentially expressed genes. In conclusion, this study could provide comprehensive information about the dysregulated genes and biological pathways in PBMCs which might be responsible for disease tolerance in B. indicus cattle.

Differentially expressed microRNAs in biochemically characterized FrieswalTM crossbred bull semen.

In addition to the transmission of paternal genome, spermatozoa also carry coding as well as noncoding microRNAs (miRNAs) into the female oocyte during the process of biological fertilization. Based on RNA deep sequencing, a total 28 number of differentially expressed miRNAs were cataloged in categorized FrieswalTM crossbred (Holstein Friesian X Sahiwal) bull semen on the basis of conception rate (CR) in field progeny testing program. Validation of selected miRNAs viz. bta-mir-182, bta-let-7b, bta-mir-34c and bta-mir-20a revealed that, superior bull semen having comparatively (p < .05) lower level of all the miRNAs in contrast to inferior bull semen. Additionally, it was illustrated that, bta-mir-20a and bta-mir-34c miRNAs are negatively (p < .01) correlated with seminal plasma catalase (CAT) activity and glutathione peroxidase (GPx) level. Interactome studies identified that bta-mir-140, bta-mir-342, bta-mir-1306 and bta-mir-217 can target few of the important solute carrier (SLC) proteins viz. SLC30A3, SLC39A9, SLC31A1 and SLC38A2, respectively. Interestingly, it was noticed that all the SLCs were significantly (p < .05) expressed at higher level in superior quality bull semen and they are negatively correlated (p < .01) with their corresponding miRNAs as mentioned. This study may reflect the role of miRNAs in regulating few of the candidate genes and thus may influence the bull semen quality traits.

Microbial, environmental and anthropogenic factors influencing the indoor microbiome of the built environment.

A built environment is a human-made environment providing surroundings for human occupancy, activities, and settlement. It is supposed to safeguard humans from all undesirable and harmful pollutants; however, indoor concentrations of some pollutants are much greater than that of the outdoors. Bioaerosols infiltrate from the outdoors in addition to many indoor sources of bioaerosols including the use of various chemicals as well as activities like cooking, smoking, cleaning, or even normal movement. They are also associated with a number of serious health concerns. Various ecological factors associated with the generation, the persistence as well as the dispersal of these microbial components of indoor bioaerosols, are discussed in this review, that have not been considered all together till now. The factors like microbial taxa, environmental factors, and anthropogenic activities (human occupancy, activities, and impact of urbanization) are addressed in the review. Effects of both indoor environmental factors like architectural design, lighting, ventilation, temperature, humidity, indoor/outdoor ratio, particulate matter, indoor chemistry as well as outdoor environmental factors like geography, seasons, and meteorology on the microbial concentrations have been discussed. Efforts are underway to design selective pressures for microbes to create a healthy symbiotic built microbiome as the "right" indoor microbiome is a "healthy" indoor microbiome.

Risk assessment of low arsenic exposure using biomarkers of oxidative and genotoxic stress in a piscine model.

The high level exposure to arsenic induces marked oxidative and genotoxic stress. However, information on the potential of low level arsenic exposure in this context is still scanty. In the present study, the extent of oxidative stress and genetic toxicity induced by low arsenic exposure was explored in freshwater fish Channa punctatus. Fish were exposed to low levels of arsenic (10 and 50 µg L-1) as well as to its high level (500 µg L-1) using sodium arsenite in aquaria water for 14 consecutive days. The TBARS assay for lipid peroxidation exhibited the increased occurrence of oxidative damage in the erythrocytes of fish at both the lower and higher levels of arsenic exposure. The level of reduced glutathione was also elevated in all the three arsenic exposed groups of fish compared to control. In contrast, significant decline was observed in the levels of three major antioxidant enzymes namely, superoxide dismutase, catalase and glutathione peroxidase, upon exposure to higher as well as lower levels of arsenic. Significant increases in micronucleus induction were found in the erythrocytes of fish even at the low levels of arsenic exposure. The study further revealed the occurrence of DNA fragmentation in the erythrocytes of fish at low arsenic exposures as well. The low level exposure to arsenic (using sodium arsenite), therefore, appeared to be capable of inducing noticeable oxidative stress as well as potential genotoxic effect in Channa punctatus. Moreover, the ability of arsenic to induce oxidative stress invariably appeared correlated with its genotoxic potential.

The mRNA expression of immune-related genes in crossbred and Tharparkar cattle in response to in vitro infection with Theileria annulata.

Tropical theileriosis is a major protozoan disease of cattle and is associated with high rates of morbidity and mortality. Indigenous cattle (Bos indicus) are less affected by this disease than exotic and crossbred cattle. Genetic basis of resistance to tropical theileriosis in indigenous cattle is not well studied. Recent reports suggest that number of immune response genes expressed differentially in exotic and indigenous breeds play an important role in breed specific resistance to tropical theileriosis. Such studies comparing expression of these genes in crossbred cattle and indigenous cattle are lacking. The present study compares the mRNA expression of immune-related genes in response to Theileria annulata infection in indigenous and crossbred cattle. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of indigenous (Tharparkar) and crossbred (HF/BS/Jersey × Hariana) cattle and challenged with prepared ground-up tick supernatant carrying Theileria annulata sporozoites in vitro. qPCR was employed to measure relative mRNA expression of toll-like receptor 10 (TLR10), signal-regulatory protein alpha (SIRPA), MHC class II DQα (BoLA-DQA), musculoaponeurotic fibrosarcoma (MAF) and prion protein (PRNP) genes in infected and control PBMCs from crossbred and indigenous cattle. On the basis of comparative fold change analysis, significant up-regulation in SIRPA, PRNP and MHC DQα genes and significant down-regulation in TLR10, cMAF and MAFB genes in crossbreds as compared to indigenous cattle was observed. Results of the present study suggest that breed specific differential expression of the genes under study may contribute to the breed specific resistance to Theileria annulata infection in indigenous cattle compared to crossbred cattle.

The influence of tumour blood perfusion variability on thermal damage during nanoparticle-assisted thermal therapy.

PURPOSE: This study investigates the influence of blood perfusion variability within a tumour and the surrounding healthy tissue during nanoparticle-assisted thermal therapy. It seeks to define ideal therapeutic parameters for a wide range of perfusion rates to attain the desired thermal damage. MATERIAL AND METHODS: Pennes' bioheat model and the Arrhenius model are used to evaluate the thermal damage for a two-dimensional tumour surrounded by healthy tissue. A wide range of tumour perfusion rates were modelled, ranging from moderate to high perfusion in both a homogenously and a heterogeneously perfused tumour. RESULTS: For low perfusion rates, a temporal variation in blood perfusion does not critically influence the thermal damage. For moderately and highly perfused tumours, temporal variation in blood perfusion extends the thermal damage zone by 25-52% compared to a constant perfusion rate. For the tumour size and perfusion conditions under consideration, the ideal therapeutic parameters were found to be irradiation intensity of 1 W/cm(2), and irradiation duration of 105-150 s, for a nanoparticle volume fraction of 0.001%. CONCLUSIONS: It is concluded for low perfusion rates that due to shorter therapeutic duration, nanoparticle-assisted thermal therapy is relatively insensitive to changes in the perfusion rate during the therapy. For moderately and highly perfused tumours, a constant perfusion under-predicts the real thermal damage zone. This study concludes that for moderately and highly perfused tumours the spatial as well as temporal blood perfusion dynamics should be carefully accounted for to get a realistic estimate of thermal damage zone.

Assessment of arsenic-induced DNA damage in goldfish by a polymerase chain reaction-based technique using random amplified polymorphic DNA markers.

Arsenic is a groundwater contaminant of global concern. It is a potent human carcinogen, and its marked genotoxic effects have been reported in several human and animal studies. The present work investigates the applicability of the random amplified polymorphic DNA (RAPD) assay to study the DNA-damaging effects of arsenic at low-level exposure in goldfish Carassius auratus. Four experimental groups of fish, A, B, C and D, were exposed to 0, 10, 50, and 1,000 µg L(-1) of arsenic, respectively, in aquaria water for 15 consecutive days. Genomic DNA extraction was followed by RAPD-polymerase chain reaction amplification for each fish separately. One arbitrary decamer primer (PUZ-19) of 33 primers used appeared as the most informative and was capable of exhibiting marked alterations in RAPD profiles between arsenic-exposed and unexposed (control) samples. Different sets of 11 loci were amplified in various experimental groups with four clear polymorphic bands by the primer PUZ-19. The X and XIII amplification loci, which were prominent in the unexposed group, failed to appear in the arsenic-exposed groups. In contrast, the I and XI RAPD bands appeared as new amplification loci in all of the exposed groups. Such alterations in genomic DNA, however, did not exhibit a clear dose-dependent tendency. The RAPD assay, because of its efficacy to unmask alterations in genomic DNA induced by arsenic at low exposure level of 10 µg L(-1), appears to be a sensitive and potential tool for detecting arsenic genotoxicity.

Investigation on nanoparticle distribution for thermal ablation of a tumour subjected to nanoparticle assisted thermal therapy.

This study investigates the effect of the distribution of nanoparticles delivered to a skin tumour for the thermal ablation conditions attained during thermal therapy. Ultimate aim is to define a distribution of nanoparticles as well as a combination of other therapeutic parameters to attain thermal ablation temperatures (50-60 °C) within whole of the tumour region. Three different cases of nanoparticle distributions are analysed under controlled conditions for all other parameters viz. irradiation intensity and duration, and volume fraction of nanoparticles. Results show that distribution of nanoparticles into only the periphery of tumour resulted in desired thermal ablation temperature in whole of tumour. For the tumour size considered in this study, an irradiation intensity of 1.25 W/cm(2) for duration of 300 s and a nanoparticle volume fraction of 0.001% was optimal to attain a temperature of ≥53 °C within the whole tumour region. It is concluded that distribution of nanoparticles in peripheral region of tumour, along with a controlled combination of other parameters, seems favourable and provides a promising pathway for thermal ablation of a tumour subjected to nanoparticle assisted thermal therapy.

Induction of sperm impairments in mice as a sensitive biomarker of arsenic toxicity.

The ubiquitous presence of arsenic (a toxic metalloid) in our environment, particularly in our drinking water, is a serious health hazard of global concern. The present work deals with the assessment of arsenic toxicity through the analysis of induced sperm impairments in sperm head morphology and sperm count in mice at low exposures compared to the magnitude of response at high exposure levels. The animals were exposed to four doses of arsenic, ranging from lowest dose of 0.3 µg kg(-1) day(-1) (the human reference dose) to higher dose of 30 µg kg(-1) day(-1) for 15 consecutive days. The epididymal sperms were harvested after one spermatogenic cycle on the 36th day and were scored for the presence of any abnormality in their head morphology as well as changes in their count. Exposure to arsenic significantly induced, in a dose-dependent manner, increases in the frequency of sperms with abnormal head morphology from 5.12 % in control to 9.23 % in lowest dose group and 23.02 % in highest dose group. In contrast, the mean sperm counts in the epididymal wash were decreased from 6.05 million per milliliter in the control to 4.95 million per milliliter in the lowest dose group and 3.07 million in the highest dose group. The analysis of sperm impairments in mice was, therefore, found to be a highly sensitive assay to assess arsenic toxicity, exhibiting a marked male reprotoxic effect of arsenic even at its low exposure levels including the human reference dose.

Deciphering genetic diversity in conserved cattle bulls to achieve sustainable development goals.

The primary objective of Sustainable Development Goal target 2.5 established by the United Nations is to ensure the preservation of genetic diversity in domesticated animals. The ICAR-National Bureau of Animal Genetic Resources in India has been actively engaged in the conservation of cattle and buffalo bull semen for long-term storage. This present study aimed to assess the genetic diversity present in the conserved cattle bull semen, which would aid in determining the most suitable strategy for future conservation management. A total of 192 bull semen belonging to 19 cattle breeds were selected to evaluate genetic diversity using 17 pairs of FAO recommended microsatellite primers. Total 267 alleles were detected across all the samples which indicates substantial amount of allelic variation is being maintained in conserved bulls. Further, all cattle bulls semen conserved showed higher observed heterozygosity than expected heterozygosity which indicates excess genetic diversity in all the populations. The FST, F IT and FIS value across the loci and population is 0.146 ± 0.009, 0.054 ± 0.038, and - 0.105 ± 0.035, respectively, which suggests lack of inbreeding in conserved cattle bull semen. This study has established genetic diversity in conserved cattle semen samples to achieve sustainable development goals. In addition, it provides compelling evidence that the current approach for conserving cattle bull semen is heading in the correct direction.

Fish micronucleus assay to assess genotoxic potential of arsenic at its guideline exposure in aquatic environment.

The exposure to arsenic, a potential genotoxic carcinogen in humans, via drinking water is a serious worldwide health hazard. The arsenic content of 10 µg L(-1) in drinking water, however, has been established as its guideline standard (maximum contaminant limit) that has been estimated to pose minimum risk to cancer. Since micronucleus induction in the erythrocytes of fish is a sensitive indicator of genotoxic agents in water, the piscine micronucleus assay was used in the present experiment to assess the genotoxic potential of arsenic at its various exposure levels including the guideline value for drinking water. The experiments were conducted in two different species of fishes, the pond murrel (Channa punctatus) and the goldfish (Carassius auratus). Significant increases in the frequency of micronucleated erythrocytes were documented in a dose-dependent manner in both Channa and Carassius. The fishes, however, exhibited variations in inter-specific sensitivity to micronucleus induction following arsenic exposure. The exposure level of arsenic at its guideline value for drinking water, therefore, exhibited marked genotoxicity in fishes.

Role of optical coefficients and healthy tissue-sparing characteristics in gold nanorod-assisted thermal therapy.

PURPOSE: This study seeks to define parameters for gold nanorod assisted thermal therapy, to achieve the thermal ablation temperature (50-60°C) in the tumour region and spare healthy tissue surrounding the tumour. Also, a criterion for size selection of gold nanorods is described based on the role of optical coefficients. THEORY AND METHODS: In this study a tissue domain (comprising a 3 mm tumour and 7 mm of surrounding healthy tissue) embedded with gold nanorods is irradiated with electromagnetic radiation within the therapeutic wavelength band. Optical interaction is captured using light scattering theory (Mie-electrostatic approach). The resulting temperature field is evaluated using Penne's bioheat model. The effect of key parameters, namely irradiation intensity, irradiation duration and volume fraction, on tissue temperature is also modelled numerically. RESULTS: With increasing nanorod diameter - from 5 nm to 15 nm - the scattering coefficient increases ∼76 times as compared to a 1.7-fold increase in absorption coefficient. Scattering is considerably minimised by having smaller gold nanorods of 5 nm diameter. For this study, gold nanorods of 5 nm diameter and volume fraction 0.001%, irradiated with 50 W/m(2)-nm for 250 s ablated the tumour as well as spare healthy tissue 2 mm beyond the tumour region. CONCLUSION: Overall it may be concluded that tumour ablation as well as surrounding healthy tissue-sparing (within millimetres immediately adjacent to the tumour) can be achieved through a combination of specified parameters, namely diameter and volume fraction of gold nanorods, irradiation intensity and duration.

Attitudes and practices of auxiliary nurse midwives and accredited social health activists in Uttar Pradesh and Bihar regarding polio immunization in India.

Although India was removed from the list of polio endemic countries in January 2012, maintaining the focus on polio vaccination is critically important to prevent reintroduction of the virus. In 2009-2010, we conducted a study to assess the attitudes and practices of frontline health workers in India regarding polio immunization in Uttar Pradesh and Bihar. More than 95% of auxiliary nurse midwives (ANMs) and accredited social health activists (ASHAs) agreed that polio supplementary immunization campaigns helped in increasing acceptance of all vaccines. The majority of ANMs (60-70%) and ASHAs (56-71%) believed that polio immunization activities benefitted or greatly benefitted other activities they were carrying out. Less than 5% of ANMs and ASHAs felt they were very likely to face resistance when promoting or administering polio vaccine. This study provides information that may be useful for programs in other countries for polio eradication and in India for measles elimination.

Genotoxic potential of arsenic at its reference dose.

Arsenic, a highly hazardous contaminant in our drinking water, accounts for various toxic effects (including cancer) in human. However, intake of arsenic @0.3 µg kg(-1)day(-1) through drinking water, containing arsenic at its guideline value or maximum contaminant limit (10 µg L(-1)), has been estimated to pose very little or no measurable risk to cancer in humans. The value also appears to be equal to the human reference dose (or index dose) of arsenic based on human skin toxicity data. The present work was a quantitative assessment of the genotoxic potential of arsenic in mice at doses equivalent to its human reference dose as well as its multiples. Significant increases in the frequencies of chromosome abnormalities in the bone marrow cells were registered over the control level upon exposure to all the doses of arsenic including its reference dose (or index dose). The assessment of arsenic genotoxicity in humans at low doses will therefore be highly instrumental in establishing a permissible limit of arsenic in drinking water.

Cytogenetic toxicity of Aloe vera (a medicinal plant).

The cytogenetic toxicity of the crude leaf extract of Aloe vera, a medicinal plant, was evaluated in two test systems, onion and Swiss albino mice, using their root tip meristematic and bone marrow cells, respectively. No significant increase in structural abnormalities in chromosomes was observed, but a marked increase in cells with chromosome-number anomalies was found. The extract, however, significantly increased the mitotic index of both cell types.

Bacteriophage therapeutics to confront multidrug-resistant Acinetobacter baumannii - a global health menace.

We have already entered the post-antibiotic era as the outbreaks of numerous multidrug-resistant strains in the community as well as hospital-acquired infections are ringing alarm bells in the health sector. Acinetobacter baumannii is one such pathogen that has been considered a worldwide threat as it acquires multidrug resistance. It is one of the most challenging hospital-acquired pathogens as World Health Organization has listed carbapenem-resistant A. baumannii as a critical priority pathogen with limited therapeutic options. There is an urgent need to develop novel strategies against such pathogens to tackle the global crisis. Bacteriophages (phages), especially the lytic ones have re-emerged as a potential therapeutic approach. This review encompasses vast majority of phages against A. baumannii strains with special references related to single phage or monophage therapy, use of phage cocktails, combination therapy with antibiotics, use of phage-derived enzymes like endolysins and depolymerases to combat the pathogen and explore their therapeutic aspects. The concurrent ecological as well as evolutionary interplay between the phages and host bacteria demands in depth-research and knowledge, so as to utilize the maximum potential of the bacteriophage therapy.

Eco-evolutionary impact of ultraviolet radiation (UVR) exposure on microorganisms, with a special focus on our skin microbiome.

Sunlight is pivotal for our survival, and daily UV exposure has impacted the evolutionary course of all forms of life, from microorganisms to humans. Deciphering the role of UVR in regulating the microbial dynamics of environmental and host-associated microbes is crucial. UVR may be responsible for affecting skin pathology by influencing the skin microbiome, both qualitatively and quantitatively, as evident in low-dose narrow-band UVB phototherapy. Some findings have suggested that the skin microbiome has immunomodulatory roles when exposed to UVR; however, its involvement in UV screening or protection has yet to be fully explored. Furthermore, numerous skin disorders are associated not only with an altered skin microbiome but also with an altered gut microbiome. Hence, the skin-gut axis needs to be in physiological homeostasis and immunological harmony. The purpose of this review is to examine the impact of natural UVR on human immunomodulatory mechanisms and the associated cutaneous microbiome, with an emphasis on interactions among UVR, skin homeostasis, vitamin D, and the related skin-gut axis. With the 'nature as an inspiration' approach, ongoing research is trying to decipher photoprotective secrets in several microbial-based natural compounds to be used as sunscreens or other topical formulations. In addition, various probiotics have also been shown to have significant antioxidant, antiwrinkle, and antiaging effects that ameliorate UV-induced cellular and molecular damage, as highlighted in the review. These cosmetics, nutricosmetics, and probiotaceuticals will undoubtedly be next-generation solutions against photoaging and maintaining skin health.