Human Deaths Research Articles

The Flavonoid Agathisflavone Attenuates Glia Activation After Mechanical Injury of Cortical Tissue and Negatively Regulates Both NRLP3 and IL-1β Expression

Traumatic brain injury (TBI) has a complex and multifactorial pathology and is a major cause of death and disability for humans. Immediately after TBI, astrocytes and microglia react with complex morphological and functional changes known as reactive gliosis to form a glial scar in the area immediately adjacent to the lesion, which is the major barrier to neuronal regeneration. The flavonoid agathisflavone (bis-apigenin), present in Poincianella pyramidalis leaves, has been shown to have neuroprotective, neurogenic, and anti-inflammatory effects, demonstrated in vitro models of glutamate-induced toxicity, neuroinflammation, and demyelination. In this study, we evaluated the effect and mechanisms of agathisflavone in neuronal integrity and in the modulation of gliosis in an ex vivo model of TBI. For this, microdissections from the encephalon of Wistar rats (P6-8) were prepared and subjected to mechanical injury (MI) and treated or not with daily agathisflavone (5 μM) for 3 days. Astrocyte reactivity was investigated by measuring mRNA and expression of GFAP protein in the lesioned area by immunofluorescence and Western blot. The proportion of microglia was determined by immunofluorescence for Iba-1; mRNA expression for inflammasome NRPL3 and interleukin-1 beta (IL-1β) was determined by RT-qPCR. It was observed that lesions in the cortical tissue induced astrocytes overexpressing GFAP in the typical glial scar formed and that agathisflavone modulated GFAP expression at the transcriptional and post-transcriptional levels, which was associated with a reduction of the glial scar. MI induced an increase in the proportion of microglia (Iba-1+), which was not observed in agathisflavone-treated cultures. Moreover, the flavonoid modulated negatively both the NRLP3 and IL-1β mRNA expression that was increased in the lesioned area of the tissue. These findings support the regulatory properties of agathisflavone in the control of the inflammatory response in glial cells, which can impact neuroprotection and should be considered for future studies for TB and other pathological conditions of the central nervous system.

TIR signaling activates caspase-like immunity in bacteria.

Caspase family proteases and Toll/interleukin-1 receptor (TIR)-domain proteins have central roles in innate immunity and regulated cell death in humans. We describe a bacterial immune system comprising both a caspase-like protease and a TIR-domain protein. We found that the TIR protein, once it recognizes phage invasion, produces the previously unknown immune signaling molecule adenosine 5'-diphosphate-cyclo[N7:1'']-ribose (N7-cADPR). This molecule specifically activates the bacterial caspase-like protease, which then indiscriminately degrades cellular proteins to halt phage replication. The TIR-caspase defense system, which we denote as type IV Thoeris, is abundant in bacteria and efficiently protects against phage propagation. Our study highlights the diversity of TIR-produced immune signaling molecules and demonstrates that cell death regulated by proteases of the caspase family is an ancient mechanism of innate immunity.

Replication-incompetent VSV-based vaccine elicits protective responses against SARS-CoV-2 and influenza virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses lead to severe respiratory illnesses and death in humans, exacerbated in individuals with underlying health conditions, remaining substantial global public health concerns. Here, we developed a bivalent replication-incompetent single-cycle pseudotyped vesicular stomatitis virus vaccine that incorporates both a prefusion-stabilized SARS-CoV-2 spike protein lacking a furin cleavage site and a full-length influenza A virus neuraminidase protein. Vaccination of K18-hACE2 or C57BL/6J mouse models generated durable levels of neutralizing antibodies, T cell responses, and protection from morbidity and mortality upon challenge with either virus. Furthermore, the vaccine provided heterologous protection upon challenge with a different influenza virus strain, supporting the advantage of using NA to increase the breadth of vaccine protection. Now, no bivalent vaccine is approved for use against both SARS-CoV-2 and influenza virus. Our study supports using this platform to develop safe and efficient vaccines against multiple viruses.

Diagnostic and prognostic values of tsRNAs in lung cancer: a meta-analysis

BackgroundLung cancer (LC) is the leading cause of cancer-related death in humans. tRNA-derived small RNA (tsRNA) is a novel biomarker that plays a crucial role in the genesis and development of LC. In this study, we aimed to investigate the value of differentially expressed tsRNAs in LC through meta-analysis.MethodsPubMed and Web of Science were searched for articles published up to January 10, 2024. Diagnostic odds ratios (DORs) and areas under the receiver operating characteristic curve (AUCs) were used to evaluate the potential of tsRNAs as diagnostic markers for LC. Furthermore, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to analyze association of tsRNAs with LC prognosis.ResultsIn total, 12 studies were included in the analysis. Our results indicated that the combined DOR of total tsRNAs for LC diagnosis was 7.32; the AUC was 0.81. Subgroup analysis revealed that high levels of tsRNAs in serum had good diagnostic efficacy (DOR = 16.56, AUC = 0.88). Moreover, a high tsRNAs level was associated with a worse prognosis in LC patients (HR = 1.59, 95% CI: 1.33–1.90).ConclusionOur findings suggest that a high tsRNAs level has potential value for diagnosis and prognosis of LC patients. However, further high-quality studies are needed to validate our results.

Development of the house fly, Musca domestica L. (Diptera: Muscidae), on pork tissue at two temperatures.

The house fly, Musca domestica, L. (Diptera: Muscidae), is a filth fly that is often associated with criminal and civil investigations surrounding abuse, neglect, and death of humans and other vertebrates. However, development data, which are crucial for determining the age of immatures collected under forensically relevant circumstances, are limited. Given the lack of data and the recognition of population-specific growth patterns, the aim of this study was to generate data for development of a M. domestica population from Texas, USA, on decomposing lean pork at 24.0°C (i.e., approximate room temperature in Texas) and 37.0°C (i.e., approximate human body temperature). As expected, fly development significantly differed between temperatures with development at the higher temperature taking significantly less time (development from egg to adult emergence occurred c. 48.5% faster at 37.0°C than at 24.0°C). The value of this dataset is demonstrated through an applied comparison with previously published data for the house fly. Differences in development times across life stages for the studies are evident, with shorter time of colonization estimations using the data published by Wang etal. (2018), especially in later life stages. These data represent the first development dataset for the house fly on decomposing flesh in North America. Furthermore, the comparison with the previously published dataset demonstrate data from this study are of value for future forensic investigations in Texas or possibly other parts of the United States where this species is encountered, as they can be used to determine time of colonization.

Rabies vaccinations at the rural-urban divide: successes and barriers to dog rabies vaccination programs from a rural and urban campaign in Zambia.

Dog vaccination against rabies is considered one of the most effective strategies at preventing human deaths from rabies and is a key strategy for eliminating dog-mediated human rabies deaths. Traditional vaccination approaches in Zambia rarely collect operational data to assess coverage and inform subsequent campaigns. Following mass vaccination campaigns in rural (Itezhi tezhi) and urban (Lusaka) communities, we evaluated vaccination coverage achieved during the campaigns and characterized and estimated the dog population in these communities. Herd immunity (i.e., 70% vaccination coverage) was not achieved in the Lusaka campaign, likely due to challenges in pre-campaign community sensitization and distance to vaccination sites in the central point campaign approach. Dog population density showed a strong exponential association with human density (R2 = 0.89). Extrapolating this relationship nationally, there are an estimated 3.2 million dogs in Zambia (human-to-dog ratio 5.8:1) with 86% residing in rural communities at a very low density of less than 6 dogs per square kilometer. As most dogs were found to reside at very low densities, unique challenges to large-scale dog vaccination approaches may impact Zambia, due to high logistical costs associated with these settings. Prioritizing vaccinations in higher-density free-roaming dog populations could maximize effectiveness in resource-limited settings. Private veterinary services were commonly utilized among surveyed dog owners in urbanized communities in Lusaka, suggesting that they are an important collaborator for achieving rabies herd immunity. With improved knowledge of dog population and ownership characteristics, Zambia is well-prepared to design more effective vaccination campaigns as the rabies elimination program expands.

Occurrence of Antibiotic-Resistant Bacteria in Urban Surface Water Sources in Bangladesh.

Infections caused by antibiotic-resistant bacteria (ARB) result in an estimated 1.27 million human deaths annually worldwide. Surface waters are impacted by anthropogenic factors, which contribute to the emergence and spread of ARB in the aquatic environment. While research on antibiotic resistance in surface waters has increased recently in developing nations, including Bangladesh, especially in aquaculture, such studies are still limited in Bangladesh compared to developed nations. In this study, bacteria strains isolated from three rivers and two lakes in Khulna city, Bangladesh were characterized for their antibiotic resistance using disk diffusion method. Of the 106 bacterial isolates from 180 surface water samples, the majority exhibited resistance to Ciprofloxacin (75.0-87.5%) and Ceftriaxone (65.6-78.1%), while resistance to Ampicillin was comparatively lower (9.4-18.8%). Notably, the prevalence of ARB was observed to be higher during the wet seasons compared to the dry seasons. The 16S rRNA gene analysis showed that Shigella flexneri was the most dominant (17.9%) bacterium among the ARB cultured from surface waters, followed by Escherichia fergusonii (12.5%), Proteus mirabilis (10.7%), and Enterobacter quasiroggenkampii (8.9%). At the genus level, Enterobacter (23.5%), Shigella (20.6%), and Escherichia spp. (14.7%) were the most abundant among the ARB in both river and lake samples. The findings of this study highlight the prevalence of antimicrobial resistance in surface water sources and suggest the need for enhanced monitoring and improved disposal practices to mitigate potential public health risks.

Toxoplasma gondii and Rabies-The Parasite, the Virus, or Both?

Toxoplasma gondii is an intracellular protozoan parasite that infects a wide range of vertebrates, including humans. Although cats are the only definitive host, any warm-blooded animal can act as a paratenic host. Throughout the years, this apicomplexan parasite has been studied due to its wide prevalence, zoonotic potential, and host behavioral alterations. Known for its neurological alterations, the rabies virus is one of the most recognized types of zoonosis that, although preventable, still causes deaths in humans and animals worldwide. Due to the overlapping clinical signs of these two pathogens, the objective of this study was to evaluate the prevalence of T. gondii DNA in cerebellum tissue collected for rabies testing; cerebellum tissue from diverse animals is often submitted for this purpose. Between May 2022 and April 2024, we tested 903 cerebellum tissue samples from 22 animal species submitted for rabies testing to the Oklahoma Animal Diagnostic Disease Laboratory. Overall, T. gondii prevalence was 3.96%, with 1.8% found in cats (Felis catus), 1.7% in dogs (Canis familiaris), 0.3% in skunks (Mephitis mephitis), and 0.2% in infected cattle (Bos taurus). Analysis among T. gondii-positive hosts revealed a statistically significant difference in dogs when comparing neutered vs. intact males, with 7.94% (5/63) T. gondii-positive neutered males and 1.61% (3/186) T. gondii-positive intact males (p = 0.02). All the T. gondii-positive samples were negative for rabies. Anamnesis in some of the T. gondii-positive samples included ataxia, aggression, muscle rigidity, lethargy, and seizures, with the latter also described in dogs and aggression in the positive bovine sample. The clinical signs described in the T. gondii-infected hosts can be mistaken for rabies infection; therefore, it is important to consider T. gondii as a differential diagnosis in suspected rabies cases and test for this parasite when negative rabies results are obtained.

Identification of Anthrax as the Cause of a Cluster of Unexplained Deaths, Uganda, 2023: The Role of Metagenomic Next-Generation Sequencing and Postmortem Specimens.

Between April and November 2023, 27 unexplained human deaths that presented with swelling of the arms, skin sores with black centers, difficulty in breathing, obstructed swallowing, headaches, and other body aches were reported in Kyotera District, Uganda by the Public Health Emergency Operations Center. Subsequently, the death of cattle on farms and the consumption of carcass meat by some residents were also reported. Field response teams collected clinical/epidemiological data and autopsy samples to determine the cause of deaths. Metagenomic next-generation sequencing (mNGS) and target enrichment sequencing conducted on postmortem samples confirmed Bacillus anthracis, the etiological agent of anthrax disease, as the cause of the deaths. Applying mNGS to autopsy specimens is useful as a retrospective tool for identifying high-consequence pathogens during suspected outbreaks of unknown etiology.

Inspired by “Trojan Horse” Effect to Construct a Novel Chrome‐Free Tanning Agent—Achieving the Integration of Tanning‐Dyeing and Personal Thermal Management

AbstractAmong human deaths induced by abnormal weather, ≈95% are caused by low temperatures. Personal thermal management (PTM) is more energy efficient than traditional central heating. Inspired by “Trojan War” and combined with the advantages of natural leather, a novel chrome‐free tanning agent (OMFA) with “Trojan Horse” effect is constructed based on ZrOCl2‐assisted oxidation mineral fulvic acid. It innovatively realizes the “One Stone Three Birds” integrated strategy of tanning, dyeing and PTM leather preparation. OMFA, just like a Trojan horse, brings the Zr4+ into all hierarchy of leather; as a result, OMFA is firmly fixed in leather collagen fibers by chemical cross‐linking. The shrinking temperature of resultant leather reaches 82.7 °C and the color difference is less than 0.2, showcasing good hydrothermal stability and color fastness. Moreover, the solar absorption rate of OMFA tanned leather reaches 78.3%. In the outdoor test, the surface temperature of the leather is higher 20.9 °C and 3.4 °C than the ambient temperature at noon and evening, respectively. This study is the first time to confer thermal management properties onto leather by means of tanning. This work is expected to replace chrome tanning agent, reduce dye wastewater discharge, and realize clean energy utilization.

Development of a Recombinant Fusion Vaccine Candidate Against Lethal Clostridium botulinum Neurotoxin Types A and B.

Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, are potent protein toxins that can cause botulism, which leads to death or neuroparalysis in humans by targeting the nervous system. BoNTs comprise three functional domains: a light-chain enzymatic domain (LC), a heavy-chain translocation domain (HCN), and a heavy-chain receptor-binding domain (HCC). The HCC domain is critical for binding to neuronal cell membrane receptors and facilitating BoNT internalization via endocytosis. Accordingly, it may serve as a vaccine candidate, inducing anti-BoNT-neutralizing antibodies in animals. Here, we aimed to develop a vaccine capable of simultaneously defending against both BoNT/A and B. We combined the HCC domains of botulinum neurotoxin type A (BoNT/A) and botulinum neurotoxin type B (BoNT/B) in Escherichia coli to produce a recombinant protein (rHCCB-L-HCCArHCcB) that offers dual protection against both toxins by inhibiting their receptor binding. To evaluate the efficacy of the vaccine, mice were immunized intramuscularly with rHCCB-L-HCCA plus alum thrice at 2-week intervals, followed by the assessment of immunogenicity and protective efficacy. The antibody titer in mice immunized with rHCCB-L-HCCA was significantly higher than that in mice immunized with alum alone, protecting them from the lethal challenges of BoNT/A (105 50% lethal dose, LD50) and B (103 LD50). These findings suggest that rHCCB-L-HCCA may simultaneously be an effective vaccine candidate against BoNT/A and B.

Combining genomics and epidemiology to investigate a zoonotic outbreak of rabies in Romblon Province, Philippines

AbstractRabies is a viral zoonosis that kills thousands of people annually in low- and middle-income countries across Africa and Asia where domestic dogs are the reservoir. ‘Zero by 30’, the global strategy to end dog-mediated human rabies, promotes a One Health approach underpinned by mass dog vaccination, post-exposure vaccination of bite victims, robust surveillance and community engagement. Using Integrated Bite Case Management (IBCM) and whole genome sequencing (WGS), we enhanced rabies surveillance to detect an outbreak in a formerly rabies-free island province in the Philippines. We inferred that the outbreak was seeded by at least three independent human-mediated introductions that were identified as coming from neighbouring rabies-endemic provinces. Considerable local transmission went undetected, and two human deaths occurred within 6 months of outbreak detection. Suspension of routine dog vaccination due to COVID-19 restrictions likely facilitated rabies spread from these introductions. Emergency response, consisting of awareness measures, and ring vaccination, were performed, but swifter and more widespread implementation is needed to contain and eliminate the outbreak and to secure rabies freedom. We conclude that strengthened surveillance making use of new tools such as IBCM, WGS, and rapid diagnostic tests can support One Health in action and progress towards the ‘Zero by 30’ goal.

Understanding and overcoming geographical barriers for scaling up dog vaccinations against rabies

Rabies causes 59,000 human deaths annually in over 150 countries. Mass dog vaccination (MDV) is key to controlling dog rabies, requiring 70% coverage in the susceptible dog population to eliminate rabies deaths. MDV campaigns must achieve geographical homogeneity of coverage. Although rabies elimination is feasible, operation challenges exist, especially in hard-to-reach areas. We conducted geospatial modelling to identify geographical factors affecting MDV success in terms of campaign completeness and vaccination coverage across 25 districts in south-eastern Tanzania. From October 2016 to January 2017, about 81,000 dogs were vaccinated in 1,379 (68%) villages within these districts. Multivariable regression analysis revealed that land cover, residence, poverty, and elevation were associated with campaign completeness. The odds of achieving completeness in croplands were 1.75 times higher compared to forests. Vaccination coverage was influenced by residence, area, poverty index, and elevation, with urban areas having lower odds of achieving coverage compared to rural areas. Coverage probabilities exceeding 70% were lower on islands, highlands, urban areas, and areas bordering protected areas. As the 2030 deadline for "zero dog-mediated human rabies deaths" approaches, operational and logistical challenges in MDV campaigns persist. Our data provide insights into MDV success and failure, guiding future control efforts to improve their effectiveness.

Diffuse Axonal and Vascular Pathology in the Gyrencephalic Brain after High-Energy Blunt Injury: Clinicopathological Correlations Involving the Brainstem.

Traumatic brain injury (TBI) after high-energy, behind helmet blunt trauma (BHBT) is an important but poorly understood clinical entity often associated with apnea and death in humans. In this study, we use a swine model of high-energy BHBT to characterize key neuropathologies and their association with acute respiratory decompensation. Animals with either stable or critical vital signs were euthanized within 4 h after injury for neuropathological assessment, with emphasis on axonal and vascular pathologies in the brainstem. The majority of cases were characterized by fractures of the cranium at or about the impact site, extensive subarachnoid hemorrhages, coup and contrecoup contusions, and primarily diffuse axonal and vascular lesions throughout the cerebrum, particularly in the brainstem. Absence of spontaneous respiration that was encountered frequently was associated with both severity of impact and the severity of brainstem axonal and vascular lesions. A focused regional examination of brainstem pathology indicated a link between adverse outcomes and diffuse axonal lesions within the medial medulla or vascular lesions within the anteroventral brainstem, a pattern suggesting that injury to brainstem respiratory centers may play a role in apnea following BHBT. In addition, while the overall burden of diffuse axonal and vascular pathologies correlated with each other, we found minimal overlap in their regional distribution. Our findings indicate that high-energy, blunt-force impact TBI causes diffuse lesions in axons and blood vessels associated with poor outcomes. They also suggest that axons and vessels may have distinct responses to tissue deformation and that commonly used markers of vascular pathology, for example, in diagnostic radiology, cannot be used as direct surrogates of diffuse axonal injury. In concert, our study underscores the role of regional axonal and vascular injuries in the brainstem in acute respiratory decompensation after high-rate blunt TBI, even in the presence of head protection; it also emphasizes the importance of detailed clinicopathological work in complex brains in the field of TBI.

Targeted Nanotherapy by Vinblastine-Loaded Chitosan-Coated PLA Nanoparticles to Improve the Chemotherapy via Reactive Oxygen Species to Hamper Hepatocellular Carcinoma.

Liver cancer is a prevalent and significant cause of death in humans. The use of novel biodegradable materials for various biomedical applications is being recently recommended as complementary as well as alternative solution for traditional chemotherapy. This study focuses on the synthesis of biodegradable nanocarriers [chitosan-coated poly(lactic acid) NPs (Cht-PLA NPs)] for the delivery of an anticancer drug vinblastine (Vbx) and to evaluate its therapeutic potential in human hepatocellular carcinoma (HepG2) cells. The Cht-PLA NPs were synthesized using the nanoprecipitation method and characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential techniques. The results showed that the nanoparticle sizes are in the range of 100-200 nm with positive surface charge. The release profile of the synthesized nanoformulation showed controlled release of the Vbx drug for 72 h. The anticancer efficacy of the synthesized nanoformulation was assessed on the HepG2 cell lines. The in vitro cytotoxicity study revealed that the Vbx-loaded Cht-PLA NPs showed higher toxicity with an increase in concentration as compared to the Vbx alone. Additionally, an in vitro cellular uptake study revealed higher internalization as compared to the drug alone due to the chitosan coating. Further, the ability to stimulate the reactive oxygen species (ROS) generation and variation in mitochondrial membrane potential at the IC50 concentration of Vbx-loaded Cht-PLA NPs was confirmed by using 2,7-dichlorodihydrofluorescein diacetate and rhodamine 123 dyes, respectively, and were analyzed under fluorescence microscopy. Hence, the results showed that Vbx-loaded Cht-PLA NPs possess high anticancer activity due to its higher cellular toxicity, cellular uptake, increased ROS production, and disruption in mitochondrial membrane potential. All these properties of the synthesized nanoformulation suggest it's potential applications in drug delivery systems, targeting liver cancer.

Differences in Corpse Stiffness (Rigor Mortis) of Organophosphate-Induced and Ordinary (Decerebrated) Dead Wistar Rats : A Randomized Experimental Study

Corpse Stiffness (rigor mortis) is a secondary sign of death that can be used to estimate the time and cause of death. Organophosphates are the most toxic pesticides and often cause poisoning until death in humans. This study aims to determine the differences in corpse stiffness (rigor mortis) due to organophosphate poisoning and ordinary death (decerebration) using Wistar rats. The parameters of corpse stiffness (rigor mortis) used include 4 aspects: Corpse Stiffness Appearance, Perfect Formation of Corpse Stiffness, Persistent Corpse Stiffness, and Relaxation of Corpse Stiffness. Data were processed with univariate analysis and then tested with the Independent Sample T-test. There was a significant difference (p<0.05) in the duration of the appearance, perfect formation, persistent and relaxation of corpse stiffness between the control group and the treatment group. Meanwhile, there was no significant difference (p>0.05) in persistent corpse stiffness duration between the control and treatment groups, although there was a slight difference in the mean. Between ordinary and died rats due to organophosphate induction, there was a significant difference in the duration of appearance, perfect formation, and relaxation of corpse stiffness. However, there was no significant difference in the duration of persistent stiffness. Keywords: Organophosphates; Poisoning; Corpse Stiffness; Rigor Mortis

Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations.

Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antibodies ineffective. Here, we use pseudovirus deep mutational scanning to measure how all single amino-acid mutations to G affect cell entry and neutralization by a panel of antibodies. These measurements identify sites critical for rabies G's function, and define constrained regions that are attractive epitopes for clinical antibodies, including at the apex and base of the protein. We provide complete maps of escape mutations for eight monoclonal antibodies, including some in clinical use or development. Escape mutations for most antibodies are present in some natural rabies strains. Overall, this work provides comprehensive information on the functional and antigenic effects of G mutations that can help inform development of stabilized vaccine antigens and antibodies that are resilient to rabies genetic variation.

Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.

Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes. We show that these immunogens induce a pronounced, broadly neutralizing antibody response in laboratory and transgenic human antibody mice. Monoclonal human antibodies isolated from immunized human antibody mice specifically recognized the grafted epitopes and neutralized four diverse HCV strains. Our results highlight a promising strategy for developing HCV immunogens and provide an encouraging paradigm for targeting structurally flexible epitopes to improve the induction of neutralizing antibodies.

Human-Wildlife Interactions with an Emphasis on the Feral Water Buffalo and the Conservation Consequences for Indian Rhinoceros in Pobitora Wildlife Sanctuary

Interactions between humans and wildlife are common throughout the world. There are often conflicts between humans and wildlife, particularly in areas were human settlements and agricultural lands border protected wildlife habitats. There is often crop damage and livestock predation caused by these conflicts, as well as human injuries or deaths, which can present significant challenges for conservation efforts and local communities. In this study, we examined the phenomenon of buffaloes wandering into the fringe areas of Pobitora Wildlife Sanctuary in order to understand the interaction between Feral Water Buffaloes and humans. These occurrences were studied to determine the causes and measures taken by local farmers to prevent them. This study involved field surveys, open-ended questionnaires, and community engagement over the course of eight months between July 2023 and February 2024. Based on our research, we identified zones of human-buffalo interaction within a 7-kilometer radius of the sanctuary where the most significant impacts occurred. Solitary buffaloes, rhinoceroses, and buffalo groups frequently stray out of the sanctuary, escalating tensions among villagers. Particularly solitary buffaloes posed a greater threat to humans than herds. In the Pobitora Wildlife Sanctuary, cropping patterns, agricultural practices, and wildlife behavior have changed significantly, highlighting the need for targeted mitigation measures in order to maintain a peaceful coexistence between humans and wildlife and to maintain rhinoceros’ populations. Keywords: Human-Wildlife interaction, Pobitora Wildlife Sanctuary, Feral Water Buffalo, Rhino, Conservation.

Nanocarriers for Delivery of Anticancer Drugs: Current Developments, Challenges, and Perspectives.

Cancer, the most common condition worldwide, ranks second in terms of the number of human deaths, surpassing cardiovascular diseases. Uncontrolled cell multiplication and resistance to cell death are the traditional features of cancer. The myriad of treatment options include surgery, chemotherapy, radiotherapy, and immunotherapy to treat this disease. Conventional chemotherapy drug delivery suffers from issues such as the risk of damage to benign cells, which can cause toxicity, and a few tumor cells withstand apoptosis, thereby increasing the likelihood of developing tolerance. The side effects of cancer chemotherapy are often more pronounced than its benefits. Regarding drugs used in cancer chemotherapy, their bioavailability and stability in the tumor microenvironment are the most important issues that need immediate addressing. Hence, an effective and reliable drug delivery system through which both rapid and precise targeting of treatment can be achieved is urgently needed. In this work, we discuss the development of various nanobased carriers in the advancement of cancer therapy-their properties, the potential of polymers for drug delivery, and recent advances in formulations. Additionally, we discuss the use of tumor metabolism-rewriting nanomedicines in strengthening antitumor immune responses and mRNA-based nanotherapeutics in inhibiting tumor progression. We also examine several issues, such as nanotoxicological studies, including their distribution, pharmacokinetics, and toxicology. Although significant attention is being given to nanotechnology, equal attention is needed in laboratories that produce nanomedicines so that they can record themselves in clinical trials. Furthermore, these medicines in clinical trials display overwhelming results with reduced side effects, as well as their ability to modify the dose of the drug.