Exploring the underlying correlation between microbiota, immune system, hormones, and inflammation with breast cancer and the role of probiotics, prebiotics and postbiotics.

According to recent research, bacterial imbalance in the gut microbiota and breast tissue may be linked to breast cancer. It has been discovered that alterations in the makeup and function of different types of bacteria found in the breast and gut may contribute to growth and advancement of breast cancer in several ways. The main role of gut microbiota is to control the metabolism of steroid hormones, such as estrogen, which are important in raising the risk of breast cancer, especially in women going through menopause. On the other hand, because the microbiota can influence mucosal and systemic immune responses, they are linked to the mutual interactions between cancer cells and their local environment in the breast and the gut. In this regard, the current review thoroughly explains the mode of action of probiotics and microbiota to eradicate the malignancy. Furthermore, immunomodulation by microbiota and probiotics is described with pathways of their activity.

UV-spectrophotometric Optimization of Temperature, pH, Concentration and Time for Eucalyptus Globulus Capped Silver Nanoparticles Synthesis, their Characterization and Evaluation of Biological Applications.

Morphology (size, shape) and structural variations (bonding pattern, crystallography, and atomic arrangements) have significant impacts on the efficacy of the metallic nanoparticles. Fabrication of these metal nanoparticles through green synthesis using plant extracts has increased attention due to their low cost, less hazardous byproducts, and multiple applications. In present study, Eucalyptus globulus extract was used to synthesize silver nanoparticles (AgNPs). Change of color from light brown to reddish brown and UV-visible spectral peak at 423 nm confirmed the formation of AgNPs. The shifting of FTIR spectra peaks indicated the potential role of the functional groups in extract as capping agents. The DLS evaluated the average size and stability of the nanoparticles while the surface morphology, size and the elemental composition of the AgNPs was established by the FESEM and EDX analysis. The SEM images revealed spherical nanoparticles of size ranging from 40-60 nm. Biogenic AgNPs showed better DPPH radical scavenging activity with IC50 (13.44 ± 0.3) as compared to leaves extract with IC50 (10.57 ± 0.2). The synthesized AgNPs showed higher zones of inhibition (ZOI) by well diffusion method against Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Results of present study highlights the potential benefits of Eucalyptus globulus leaves extract-based AgNPs for various biomedical uses.

Pharmacological and immunomodulatory modes of action of medically important phytochemicals against arthritis: A molecular insight.

Arthritis is a common illness that affects joints and it may result in inflammation and pain. Even though arthritis usually affects older people, it can also affect children, adults, and both genders. Numerous arthritic mouse models have been developed but the CIA model of rheumatoid arthritis (RA) has received the most attention. With the use of steroids, DMARDs, and NSAIDs, therapy objectives such as reduced disease incidence and better pain management are achieved. Long-term usage of these therapeutic approaches may have negative side effects. Herbal medications are the source of several medicinal substances. Studies have explored the potential benefits of medicinal plants in treating RA. These benefits include up-regulating antioxidant potential, inhibiting cartilage degradation, down-regulating inflammatory cytokines such as NF-kB, IL-6, and TNF-α, and suppressing oxidative stress. In this review, we systematically discuss the role of traditional medicinal plants in rheumatoid arthritis (RA) disease treatment. The role of different medicinal plants such as Curcuma longa, Syzygium aromaticum, Zingiber officinale and Withania somnifera, against arthritis is discussed in this review.

Chemoprotective and immunomodulatory potential of Lactobacillus reuteri against cadmium chloride-induced breast cancer in mice.

INTRODUCTION: The current study aimed to investigate the role of probiotic Lactobacillus reuteri for the treatment and prevention of breast cancer. MATERIALS AND METHODS: Breast cancer was induced by using Cadmium Chloride (Cd) (2 mg/kg) in group II. Tamoxifen was administered to group III. Group IV was treated with Lactobacillus reuteri. Group V was treated with Cd for one month and divided into three subgroups including VA, VB, and VC which were treated with tamoxifen, Lactobacillus reuteri, and tamoxifen + Lactobacillus reuteri, respectively. RESULTS: Significantly higher levels of TNF-α (40.9 ± 4.2 pg/mL), IL-6 (28.0 ± 1.5 pg/mL), IL-10 (60.2 ± 2.0 pg/mL), IFN-γ (60.2 ± 2.0 pg/mL), ALAT (167.2 ± 6.2 U/l), ASAT (451.6 ± 13.9 U/l), and MDA (553.8 ± 19.6 U/l) was observed in Cd group. In comparison, significantly lower levels of TNF-α (18.0 ± 1.1 pg/mL), IL-6 (9.4 ± 0.4 pg/mL), IL-10 (20.8 ± 1.1 pg/mL), IFN-γ (20.8 ± 1.1 pg/mL), ALAT (85.2 ± 3.6 U/l), ASAT (185 ± 6.9 U/l), and MDA (246.0 ± 7.5 U/l) were observed in group Cd + Tam + LR. Liver histopathology of the Cd group showed hemorrhage and ductal aberrations. However, mild inflammation and healthier branched ducts were observed in treatment groups. Furthermore, the renal control group showed normal glomerular tufts, chronic inflammation from the Cd group, and relatively healthier glomerulus with mild inflammation in treatment groups. CONCLUSION: Hence, the preventive and anticancerous role of probiotic Lactobacillus reuteri is endorsed by the findings of the current study.

Comparative transcriptome analysis reveals disruption of Plutella xylostella immune system by fungal peptide cyclosporin C.

The diamondback moth (Plutella xylostella), a major threat to crucifers across the globe, has developed resistance against the majority of insecticides enhancing the need for alternate control measures against this pest. Recently cyclosporin C, a secondary metabolite produced by the insect pathogenic fungus Purpeocillium lilacinum, has been reported to induce lethal and sub-lethal effects against P. xylostella. To date, little is known about the molecular mechanisms of interaction between cyclosporin C and P. xylostella immune systems. This study reports the transcriptome-based immune response of P. xylostella to cyclosprin C treatment. Our results showed differential expression of 322, 97, and 504 differentially expressed genes (DEGS) in P. xylostella treated with cyclosporin C compared to control 24, 48, and 72 h post-treatment, respectively. Thirteen DEGs were commonly expressed at different time intervals in P. xylostella larvae treated with cyclosporin C compared to control. Cyclosporin C treatment induced the down-regulated expression of majority of immune-related genes related to pattern recognition responses, signal modulation, Toll and IMD pathways, antimicrobial peptides and antioxidant responses confirming the ability to suppress immune response of P. xylostella. These results will further improve our knowledge of the infection mechanism and complex biochemical processes involved in interaction between cyclosporin C and insect immune systems.

Influence of agro-wastes derived biochar and their composite on reducing the mobility of toxic heavy metals and their bioavailability in industrial contaminated soils.

The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.

The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.

Evaluation of irrigation, drinking, and risk indices for water quality parameters of alpine lakes.

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.

Changes in life history parameters and transcriptome profile of Serangium japonicum associated with feeding on natural prey (Bemisia tabaci) and alternate host (Corcyra cephalonica eggs).

BACKGROUND: The mass production of natural predators with prolonged shelf life is a prerequisite for their field application as pest control agents. The traditional methods used for the mass production of Serangium japonicum rely heavily on the consistent supply of natural prey. This study explains the effects of B. tabaci (natural prey) and C. cephalonica eggs (alternative food) on life history and transcriptome profile of S. japanicum. METHODS: This study compares the effects of B. tabaci (natural prey) and C. cephalonica eggs (alternative food) on biology, reproduction, and predatory efficacy, and transcriptome profile of S. japanicum. RESULTS: This study revealed that S. japonicum was able to successfully complete its life cycle while feeding on B. tabaci (natural prey) and C. cephalonica eggs (alternative food). The C. cephalonica eggs fed S. japonicum individuals had longer developmental period and lower fecundity as compared to those feeding on whitefly but the survival rates (3rd instar nymphs, 4th instar nymphs and pupae) and predatory efficacy of C. cephalonica eggs fed S. japonicum individuals were significantly similar to to those feeding on whitefly.Transcriptome analysis showed that when faced with dietary changes, S. japanicum could successfully feed on C. cephalonica eggs by regulating genes related to nutrient transport, metabolism, and detoxification. Moreover, S. japanicum degraded excess cellular components through ribosomal autophagy and apoptosis, which provided sufficient materials and energy for survival and basic metabolism. CONCLUSION: Corcyra cephalonica eggs can be used as an alternate host for the predator, Serangium japonicum, as the survival rates and predatory efficacy of the predator are similar to those feeding on the natural host (B.tabaci). When faced with dietary changes, S. japanicum could successfully feed on C. cephalonica eggs as revealed by upregulation of genes related to nutrient transport, metabolism, and detoxification. These findings are of great significance for studying the functional evolution of S. japonicum in response to dietary changes.

Therapeutic and immunomodulatory role of probiotics in breast cancer: A mechanistic review.

Breast cancer has become the most prevalent and noxious type of malignancy around the globe (Giaquinto et al., 2022). Multiple clinical strategies including chemotherapy, radiotherapy, and immunotherapy have been in practice to manage breast cancer. Besides the protective roles of conventional remedial approaches, and non-reversible and deteriorative impacts like healthy cell damage, organ failure, etc., the world scientific community is in a continuous struggle to find some alternative biocompatible and comparatively safe solutions. Among novel breast cancer management/treatment options, the role of probiotics has become immensely important. The current review encompasses the prevalence statistics of breast cancer across the globe concerning developed and undeveloped counties, intestinal microbiota linkage with breast cancer, and association of breast microbiome with breast carcinoma. Furthermore, this review also narrates the role of probiotics against breast cancer and their mode of action. In Vivo and In Vitro studies under breast cancer research regarding probiotics are mechanistically explained. The current review systematically explains the immunomodulatory role of probiotics to prevent breast cancer. Last, but not the least, current review concludes the use of probiotics in the treatment of breast cancer through various mechanisms and future recommendations for molecular basis studies.

Spectrophotometrically, Spectroscopically, Microscopically and Thermogravimetrically Optimized TiO2 and ZnO Nanoparticles and their Bactericidal, Antioxidant and Cytotoxic Potential: A Novel Comparative Approach.

Current study was aimed to determine the antibacterial, antioxidant and cytotoxic potential of Titanium dioxide nanoparticles (TiO2NPs) and Zinc oxide nanoparticles (ZnONPs). Nanoparticles were characterized by UV-Vis spectrophotometry, particle size analyzer (PSA), fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The Minimum inhibitory concentration (MIC) was determined by standard agar dilution method. Antibacterial potential of nanoparticles was analyzed by standard disc diffusion method against bacterial strains including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia. Different concentrations of NPs (0.2, 0.4, 0.6, 0.8, 1.0, 1.2 and 1.4 mg/mL) were incorporated to evaluate the antimicrobial activity. Antioxidant activity and cytotoxicity of these NPs was analyzed by DPPH method and brine shrimp cytotoxicity assay, respectively. The MIC of TiO2NPs against E. coli, P. aeruginosa and K. pneumoniae was 0.04, 0.08 and 0.07 mg/mL respectively while the MIC of ZnONPs against the above strains was 0.01, 0.015 and 0.01 mg/mL. The maximum zone of inhibition was observed for K. pneumoniae i.e., 20mm and 25mm against TiO2 and ZnO NPs respectively, at 1.4 mg/mL concentration of NPs. The susceptibility of NPs against bacterial strains was evaluated in the following order: K. pneumoniae > P. aeruginosa > E. coli. The antioxidant activity of nanoparticles increased by increasing the concentration of NPs while cytotoxic analysis exhibited non-toxic effect of ZnO NPs while TiO2 had toxic effects on 1.2 and 1.4 mg/mL concentrations. Results revealed that ZnO NPs have more antibacterial and negligible cytotoxic potential in contrast to TiO2 NPs.

Evaluating the Effect of pH, Temperature and Concentration on Antioxidant and Antibacterial Potential of Spectroscopically, Spectrophotometrically and Microscopically Characterized Mentha Spicata Capped Silver Nanoparticles.

The use of traditional plants has been tremendously increased due to their higher biological impact, minimal side effects, and comparatively low cost. Moreover, the emergence of antibacterial resistance is also shifting the scientific community to reconsider herbal remedies which provide relatively safer, cheap and biologically tolerable solutions. The present research was designed to fabricate the Mentha spicata conjugated silver nanoparticles (Me-AgNPs). Furthermore, the assessment of the bactericidal potential of Me-AgNPs against various bacterial strains was another motive behind this study. Fabricated NPs were characterized with the help of the UV-Visible spectrophotometric analysis, Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). Me-AgNPs showed a significant zone of inhibition (23 ± 0.2 mm) at 8 mg/mL against Staphylococcus aureus and a 4.0 ± 0.2 mm zone of growth inhibition at 2 mg/mL against Aeromonas veronii. The stability of Me-AgNPs was assessed at various pH (4, 7 and 11) and temperatures (25 °C, 4 °C, 37 °C, 75 °C). The significant zones of inhibition (11.3 ± 0.3 mm, 8.3 ± 0.3mm, 14.3 ± 0.3 mm, and 7.6 ± 0.2 mm) were observed at pH 11 against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Klebsiella pneumoniae, respectively. Growth inhibition zones (14.0 ± 0.5 mm and 13.0 ± 0.5 mm) were also determined against B. subtilis and S. aureus at 25 °C. DPPH bioassay was conducted to find the antioxidant properties of Me-AgNPs. The highest (38.66 ± 0.2%) free radical scavenging activity was shown by Me-AgNPs at 4 mg/mL. Present study results concluded that biogenic Me-AgNPs have bactericidal as well as anti-oxidative potential. Moreover, these green synthesized Me-AgNPs could maintain their potency and stability at a wide range of pH and temperature.

Chemopreventive role of probiotics against cancer: a comprehensive mechanistic review.

Probiotics use different mechanisms such as intestinal barrier improvement, bacterial translocation and maintaining gut microbiota homeostasis to treat cancer. Probiotics' ability to induce apoptosis against tumor cells makes them more effective to treat cancer. Moreover, probiotics stimulate immune function through an immunomodulation mechanism that induces an anti-tumor effect. There are different strains of probiotics, but the most important ones are lactic acid bacteria (LAB) having antagonistic and anti-mutagenic activities. Live and dead probiotics have anti-inflammatory, anti-proliferative, anti-oxidant and anti-metastatic properties which are useful to fight against different diseases, especially cancer. The main focus of this article is to review the anti-cancerous properties of probiotics and their role in the reduction of different types of cancer. However, further investigations are in progress to improve the efficiency of probiotics in cancer treatment.

Synergistic neuroprotection by phytocompounds of Bacopa monnieri in scopolamine-induced Alzheimer's disease mice model.

BACKGROUND: Millions of people around the globe are affected by Alzheimer's disease (AD). This crippling condition has no treatment despite intensive studies. Some phytocompounds have been shown to protect against Alzheimer's in recent studies. METHODS: Thus, this work aimed to examine Bacopa monnieri phytocompounds' synergistic effects on neurodegeneration, antioxidant activity, and cognition in the scopolamine-induced AD mice model. The toxicity study of two phytocompounds: quercetin and bacopaside X revealed an LD50 of more than 2000 mg/kg since no deaths occurred. RESULTS: The neuroprotection experiment consists of 6 groups i.e., control (saline), scopolamine (1 mg/kg), donepezil (5 mg/kg), Q (25 mg/kg), BX (20 mg/kg), and Q + BX (25 mg/kg + 20 mg/kg). Visual behavioral assessment using the Morris water maze showed that animals in the diseased model group (scopolamine) moved more slowly toward the platform and exhibited greater thigmotaxis behavior than the treatment and control groups. Likewise, the concentration of biochemical NO, GSH, and MDA improved in treatment groups concerning the diseased group. mRNA levels of different marker genes including ChAT, IL-1α, IL-1 ß, TNF α, tau, and ß secretase (BACE1) improved in treatment groups with respect to the disease group. CONCLUSION: Both bacopaside X and quercetin synergistically have shown promising results in neuroprotection. Therefore, it is suggested that Q and BX may work synergistically due to their antioxidant and neuroprotective property.

Prevalence and Importance of the Necrotrophic Effector Gene ToxA in Bipolaris sorokiniana Populations Collected from Spring Wheat and Barley.

Bipolaris sorokiniana is a necrotrophic fungal pathogen that causes foliar and root diseases on wheat and barley. These diseases are common in all wheat- and barley-growing regions, with more severe outbreaks occurring under warm and humid conditions. B. sorokiniana can also infect a wide range of grass species in the family Poaceae and secrete ToxA, an important necrotrophic effector also identified other wheat leaf spotting pathogens. In this study, the prevalence and virulence role of ToxA were investigated in a collection of 278 B. sorokiniana isolates collected from spring wheat and barley in the Upper Midwest of the United States or other places, including 169 from wheat leaves, 75 from wheat roots, 30 from barley leaves, and 4 from wild quack grass leaves. ToxA was present in the isolates from wheat leaves, wheat roots, and wild grass leaves but was absent from isolates collected from barley leaves. Prevalence of ToxA in wheat leaf isolates (34.3%) was much higher than that in wheat root isolates (16%). Sequencing analysis revealed the presence of two haplotypes, with the majority being BsH2. All ToxA+ isolates produced the functional effector in liquid cultures. Pathogenicity assays revealed that ToxA+ isolates caused significantly more disease on spring wheat lines harboring Tsn1 than their tsn1 mutants, suggesting that the ToxA-Tsn1 interaction plays an important role in spot blotch development. This work confirms the importance of ToxA in B. sorokiniana populations infecting wheat and, thus, the need to eliminate Tsn1 from spring wheat cultivars to reduce susceptibility to spot blotch.

Bactericidal potential of different size sericin-capped silver nanoparticles synthesized by heat, light, and sonication.

Present study was aimed to assess the bactericidal potential of sericin-capped silver nanoparticles (Se-AgNPs) synthesized by heat, light, and sonication. Se-AgNPs were characterized by size analyzer, UV spectrophotometry, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. Average size of Se-AgNPs synthesized by heat, light and sonication was 53.60, 78.12, and 7.49 nm, respectively. All (10) bacterial strains were exposed to Se-AgNPs prepared from different methods to compare their antibacterial potentials. Largest zone of inhibition (13 ± 1.15 mm) was observed for sonication-based nanoparticles (NPs) against Klebseilla pneumoniae while the smallest zone of light assisted NPs against Serratia rubidaea (5 ± 1 mm). Bacterial strains were also exposed to different concentrations (0.2%, 0.3%, and 0.6%) of Se-AgNPs which showed largest zone (12 ± 1 mm) of inhibition for 0.4% of Se-AgNPs against Protius mirabilis and smallest zone (5 ± 1.154 mm) for 0.3% of Se-AgNPs against Escherichia coli. Furthermore, effect of different temperatures (5°C, 37°C, and 60°C) and pH (3, 7, and 12) on the efficacy and stability of Se-AgNPs was also evaluated against different bacterial strains. Sonication mediated NPs showed highest bactericidal results against K. pneumoniae (F3,8 = 6.154; p = 0.018) with smallest size NPs (7.49 nm) while lowest bactericidal results against S. rubidaea (5 ± 1 mm) were shown with largest size (78.12 nm) NPs prepared by natural light. These variations of bactericidal activities of NPs with difference size endorse that the Se-AgNPs with smallest size have highest antibacterial activity than larger size NPs. Moreover, Se-AgNPs maintain their bactericidal potency at wide range of temperature and pH, hence seemed stable.

Roman Urdu Hate Speech Detection Using Transformer-Based Model for Cyber Security Applications.

Social media applications, such as Twitter and Facebook, allow users to communicate and share their thoughts, status updates, opinions, photographs, and videos around the globe. Unfortunately, some people utilize these platforms to disseminate hate speech and abusive language. The growth of hate speech may result in hate crimes, cyber violence, and substantial harm to cyberspace, physical security, and social safety. As a result, hate speech detection is a critical issue for both cyberspace and physical society, necessitating the development of a robust application capable of detecting and combating it in real-time. Hate speech detection is a context-dependent problem that requires context-aware mechanisms for resolution. In this study, we employed a transformer-based model for Roman Urdu hate speech classification due to its ability to capture the text context. In addition, we developed the first Roman Urdu pre-trained BERT model, which we named BERT-RU. For this purpose, we exploited the capabilities of BERT by training it from scratch on the largest Roman Urdu dataset consisting of 173,714 text messages. Traditional and deep learning models were used as baseline models, including LSTM, BiLSTM, BiLSTM + Attention Layer, and CNN. We also investigated the concept of transfer learning by using pre-trained BERT embeddings in conjunction with deep learning models. The performance of each model was evaluated in terms of accuracy, precision, recall, and F-measure. The generalization of each model was evaluated on a cross-domain dataset. The experimental results revealed that the transformer-based model, when directly applied to the classification task of the Roman Urdu hate speech, outperformed traditional machine learning, deep learning models, and pre-trained transformer-based models in terms of accuracy, precision, recall, and F-measure, with scores of 96.70%, 97.25%, 96.74%, and 97.89%, respectively. In addition, the transformer-based model exhibited superior generalization on a cross-domain dataset.

Smart Detecting and Versatile Wearable Electrical Sensing Mediums for Healthcare.

A rapidly expanding global population and a sizeable portion of it that is aging are the main causes of the significant increase in healthcare costs. Healthcare in terms of monitoring systems is undergoing radical changes, making it possible to gauge or monitor the health conditions of people constantly, while also removing some minor possibilities of going to the hospital. The development of automated devices that are either attached to organs or the skin, continually monitoring human activity, has been made feasible by advancements in sensor technologies, embedded systems, wireless communication technologies, nanotechnologies, and miniaturization being ultra-thin, lightweight, highly flexible, and stretchable. Wearable sensors track physiological signs together with other symptoms such as respiration, pulse, and gait pattern, etc., to spot unusual or unexpected events. Help may therefore be provided when it is required. In this study, wearable sensor-based activity-monitoring systems for people are reviewed, along with the problems that need to be overcome. In this review, we have shown smart detecting and versatile wearable electrical sensing mediums in healthcare. We have compiled piezoelectric-, electrostatic-, and thermoelectric-based wearable sensors and their working mechanisms, along with their principles, while keeping in view the different medical and healthcare conditions and a discussion on the application of these biosensors in human health. A comparison is also made between the three types of wearable energy-harvesting sensors: piezoelectric-, electrostatic-, and thermoelectric-based on their output performance. Finally, we provide a future outlook on the current challenges and opportunities.

Modelling the impact of climate change on dengue outbreaks and future spatiotemporal shift in Pakistan.

Climate change has a significant impact on the intensity and spread of dengue outbreaks. The objective of this study is to assess the number of dengue transmission suitable days (DTSD) in Pakistan for the baseline (1976-2005) and future (2006-2035, 2041-2070, and 2071-2099) periods under Representative Concentration Pathway (RCP4.5 and RCP8.5) scenarios. Moreover, potential spatiotemporal shift and future hotspots of DTSD due to climate change were also identified. The analysis is based on fourteen CMIP5 models that have been downscaled and bias-corrected with quantile delta mapping technique, which addresses data stationarity constraints while preserving future climate signal. The results show a higher DTSD during the monsoon season in the baseline in the study area except for Sindh (SN) and South Punjab (SP). In future periods, there is a temporal shift (extension) towards pre- and post-monsoon. During the baseline period, the top ten hotspot cities with a higher frequency of DTSD are Karachi, Hyderabad, Sialkot, Jhelum, Lahore, Islamabad, Balakot, Peshawar, Kohat, and Faisalabad. However, as a result of climate change, there is an elevation-dependent shift in DTSD to high-altitude cities, e.g. in the 2020s, Kotli, Muzaffarabad, and Drosh; in the 2050s, Garhi Dopatta, Quetta, and Zhob; and in the 2080s, Chitral and Bunji. Karachi, Islamabad, and Balakot will remain highly vulnerable to dengue outbreaks for all the future periods of the twenty-first century. Our findings also indicate that DTSD would spread across Pakistan, particularly in areas where we have never seen dengue infections previously. The good news is that the DTSD in current hotspot cities is projected to decrease in the future due to climate change. There is also a temporal shift in the region during the post- and pre-monsoon season, which provides suitable breeding conditions for dengue mosquitos due to freshwater; therefore, local authorities need to take adaption and mitigation actions.

Microsponge-derived mini tablets loaded with immunosuppressive agents: Pharmacokinetic investigation in human volunteers, cell viability and IVIVC correlation.

Sirolimus, a potent immunosuppressant, has been demonstrated to have remarkable activity in inhibiting allograft rejection in transplantation. The objective of the study was to fabricate microsponge mini tablets with enhanced solubility and bioavailability. ß-Cyclodextrin and NEOCEL C91 were selected to prepare the microsponges (SLM-M) to improve the stability and solubility of sirolimus. The current study involved the quasi emulsion-solvent diffusion technique to design sirolimus-loaded microsponges that were further compressed into mini tablets 4 mm in diameter. Solid-state characterization, dissolution at different pH values, stability, and pharmacokinetic profiles with IVIVC data were analyzed in humans. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to characterize the formulations, and high-performance liquid chromatography (HPLC) was used to assess the drug stability of the compressed microsponge minitablets. The API changed from the crystalline state to an amorphous state, as shown by XRD and DSC. The compressed mini tablets showed a 4-fold enhancement in the drug dissolution profile. A toxicology investigation suggested that mini tablets were safe. In humans, the bioavailability of sirolimus compressed mini tablets from SLM-M was significantly improved. The results suggest that mini tablets prepared with ß-cyclodextrin and NEOCEL C91 by a quasi emulsion-solvent diffusion process might be an alternative way to improve the bioavailability of sirolimus. In addition, the manufacturing process is easily scalable for the commercialization of drugs to market.

A Conserved Hypothetical Gene Is Required but Not Sufficient for Ptr ToxC Production in Pyrenophora tritici-repentis.

The fungus Pyrenophora tritici-repentis causes tan spot, an important foliar disease of wheat worldwide. The fungal pathogen produces three necrotrophic effectors, namely Ptr ToxA, Ptr ToxB, and Ptr ToxC to induce necrosis or chlorosis in wheat. Both Ptr ToxA and Ptr ToxB are proteins, and their encoding genes have been cloned. Ptr ToxC was characterized as a low-molecular weight molecule 20 years ago but the one or more genes controlling its production in P. tritici-repentis are unknown. Here, we report the genetic mapping, molecular cloning, and functional analysis of a fungal gene that is required for Ptr ToxC production. The genetic locus controlling the production of Ptr ToxC, termed ToxC, was mapped to a subtelomeric region using segregating biparental populations, genome sequencing, and association analysis. Additional marker analysis further delimited ToxC to a 173-kb region. The predicted genes in the region were examined for presence/absence polymorphism in different races and isolates leading to the identification of a single candidate gene. Functional validation showed that this gene was required but not sufficient for Ptr ToxC production, thus it is designated as ToxC1. ToxC1 encoded a conserved hypothetical protein likely located on the vacuole membrane. The gene was highly expressed during infection, and only one haplotype was identified among 120 isolates sequenced. Our work suggests that Ptr ToxC is not a protein and is likely produced through a cascade of biosynthetic pathway. The identification of ToxC1 is a major step toward revealing the Ptr ToxC biosynthetic pathway and studying its molecular interactions with host factors.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.