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Significant health risks are posed by meningitis due to its rapid progression, and challenges are encountered in intravenous antibiotic administration, especially in crossing the blood‐brain barrier. To address this, an inflammation‐activated, endogenous macrophage (MΦ)‐mediated oral prodrug delivery system is developed for targeted therapeutic interventions in bacterial meningitis treatment. This system is guided by inflammation‐derived chemoattractants and triggers drug release through inflammation‐induced reactive oxygen species (ROS). Comprised of naturally derived β‐glucans conjugated with the antibiotic cefotaxime (CTX) using a ROS‐responsive linker, nanoparticles (βGlus–CTX NPs) are formed in aqueous solutions. In a mouse model of Klebsiella pneumoniae‐induced meningitis, orally administered βGlus–CTX NPs are traversed by intestinal microfold cells, surpassing the intestine‐epithelial barrier, and are absorbed by resident endogenous MΦ. These MΦ‐mediated drug delivery vehicles are then traveled through the lymphatic and circulatory systems, crossing the compromised blood‐brain barrier, ultimately reaching inflamed brain tissues, guided by their derived chemoattractants. In ROS‐rich inflamed tissue environments, the linkers in the βGlus–CTX NPs are cleaved, releasing therapeutic CTX for localized treatment. Targeted antibiotic treatment for bacterial meningitis is offered by this oral, endogenous MΦ‐mediated prodrug delivery system, overcoming the robust gut‐to‐brain biological barriers and potentially enhancing effectiveness for comfortable home‐based treatment. [ABSTRACT FROM AUTHOR]

Snakebite envenomation is a significant global health issue that requires specific antivenom treatments. In Taiwan, available antivenoms target a variety of snakes, but none specifically target Trimeresurus gracilis, an endemic and protected species found in the high mountain areas of Taiwan. This study evaluated the effectiveness of existing antivenoms against T. gracilis venom, focusing on a bivalent antivenom developed for Trimeresurus stejnegeri and Protobothrops mucrosquamatus (TsPmAV), as well as monovalent antivenoms for Deinagkistrodon acutus (DaAV) and Gloydius brevicaudus (GbAV). Our research involved in vivo toxicity testing in mice and in vitro immunobinding experiments using (chaotropic) enzyme-linked immunosorbent assays, comparing venoms from four pit viper species (T. gracilis, T. stejnegeri, P. mucrosquamatus, and D. acutus) with three types of antivenoms. These findings indicate that TsPmAV partially neutralized T. gracilis venom, marginally surpassing the efficacy of DaAV. In vitro tests revealed that GbAV displayed higher binding capacities toward T. gracilis venom than TsPmAV or DaAV. Comparisons of electrophoretic profiles also reveal that T. gracilis venom has fewer snake venom C-type lectin like proteins than D. acutus, and has more P-I snake venom metalloproteases or fewer phospholipase A2 than G. brevicaudus, T. stejnegeri, or P. mucrosquamatus. This study highlights the need for antivenoms that specifically target T. gracilis, as current treatments using TsPmAV show limited effectiveness in neutralizing local effects in patients. These findings provide crucial insights into clinical treatment protocols and contribute to the understanding of the evolutionary adaptation of snake venom, aiding in the development of more effective antivenoms for human health. Author summary: Trimeresurus gracilis is a protected pit viper species endemic to the mid-to-high-altitude mountainous areas of Taiwan. Due to the lack of a serum specifically targeting T. gracilis envenomation, patients bitten by this species currently receive treatment by employing a bivalent antivenom developed against T. stejnegeri and P. mucrosquamatus, which is believed to potentially possess cross-neutralizing effects. However, the use of the bivalent antivenom has demonstrated limited effectiveness in neutralizing local effects in patients. In response, we conducted investigations into the in vitro immunological reactivity and in vivo neutralization of T. gracilis venom using antivenoms developed against four pit viper species. Our results indicate that the bivalent antivenom was not completely effective in neutralizing T. gracilis venom. Instead, the monovalent antivenom for Gloydius brevicaudus exhibited higher in vitro binding capacities toward T. gracilis venom compared with other antivenoms. These findings may be attributed to a closer phylogenetic relationship between T. gracilis and G. brevicaudus. Furthermore, these observations have the potential to contribute to the development of more effective antivenoms, offering valuable insights for the community focused on neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Infection of pregnant cattle with both species of Bovine viral diarrhea virus (BVDV) can result in reproductive disease that includes fetal reabsorption, mummification, abortion, stillbirths, congenital defects affecting structural, neural, reproductive, and immune systems, and the birth of calves persistently infected with BVDV. Accurate diagnosis of BVDV-associated reproductive disease is important to control BVDV at the production unit level and assessment of the cost of BVDV infections in support of BVDV control programs. The purpose of the current study was to examine the stability of viral nucleic acid in fetal tissues exposed to different conditions, as measured by detection by polymerase chain reaction. Five different types of fetal tissue, including brain, skin and muscle, ear, and 2 different pooled organ samples, were subjected to conditions that mimicked those that might exist for samples collected after abortions in production settings or possible storage conditions after collection and prior to testing. In addition, tissues were archived for 36 months at −20°C and then retested, to mimic conditions that might occur in the case of retrospective surveillance studies. Brain tissue showed the highest stability under the conditions tested. The impact of fecal contamination was increased following archiving in all tissue types suggesting that, for long-term storage, effort should be made to reduce environmental contaminants before archiving. [ABSTRACT FROM AUTHOR]

A variety of chemical sensing materials and procedures for conveniently detecting mercuric ion (II) (Hg2+) have been extensively explored. The detection challenges for accomplishing a simple, fast, and low investment procedure at the ultrasensitive level are ongoing. Herein we report a quadrillionth level for detecting Hg2+ by the surface-enhanced Raman scattering (SERS) technique. There is an interaction of silver nanoparticles decorated on a zinc-oxide tetrapod structure and coated on FTO glass (Ag@ZnO-FTO) with an organic ligand. 4,4′-Dipyridyl (DPy) performed as being chemisorbed by Ag nanoparticles interacting with a pyridine ring to produce plasmonic hot spots for SERS. The morphology of the surface and porous structure of the tetrapod becomes the powerful platform for enhanced SERS performance of DPy detection. In the absence of the augmentative electrolyte, the enhancement factor for DPy is more than 107. The inhibiting of the aggregation between Ag and DPy was present following the appearance of Hg2+, demonstrated by the quenching of the SERS signal from the DPy molecules. The capability to reproduce and the selectivity of the sensing by DPy were both demonstrated. In addition, the applications for detecting Hg2+ in natural water and beverages were successfully detected. These results demonstrated the SERS sensors had the potential for detecting Hg2+ in practical use. [ABSTRACT FROM AUTHOR]

The electric properties of ferroelectric BiFeO3 (BFO) thin films with ZrO2 insulating buffer on Si substrates fabricated by chemical solution deposition were investigated. ZrO2 demonstrates excellent insulating properties on Si substrates. The metal-ferroelectric-insulator-semiconductor (MFIS) structure exhibits clockwise capacitance-voltage hysteresis loops due to the ferroelectric polarization of BFO. The maximum memory windows are 0.66 and 0.78 V, respectively, for BFO deposited on postannealed ZrO2 and on unannealed ZrO2 insulating layers. The small memory window of the BFO/ZrO2 (postannealed) MFIS is caused by significant interface trap states on the BFO/ZrO2 interface; this is supported by C-V measurements under varying frequency. [ABSTRACT FROM AUTHOR]

Naja atra , the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified V H H genes from isolated peripheral blood mononuclear cells and constructed a phage display V H H library of 1.0 × 10 7 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja . An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs., Competing Interests: The authors declare no conflict of interest.

Three groups of approximately eight-week-old beagles were vaccinated once with 1 ml of placebo vaccine (oral, n=9), 1 ml of Recombitek® Oral Bordetella (oral, n=10) or 1 ml Nobivac® Intra-Trac 3 (intranasal, 0.5 ml/nostril, n=10). Seven days after vaccination, the three groups were challenged with virulent Bordetella bronchiseptica via aerosolisation. Eight of nine dogs in the placebo group and no dogs in the Recombitek® Oral Bordetella or Nobivac® Intra-Trac 3 vaccine groups developed spontaneous cough of two or more consecutive days (disease case definition). Dogs in the Recombitek® Oral Bordetella and Nobivac® Intra-Trac 3 groups had a significantly lower incidence of disease (P<0.0001) with a 100 per cent preventable fraction. The study demonstrated that vaccination with either Recombitek® Oral Bordetella or Nobivac® Intra-Trac 3 is effective in preventing disease seven days after vaccination when compared with dogs vaccinated with a placebo., Competing Interests: Competing interests: The authors are employees of Merial (now part of Boehringer Ingelheim).

Fourteen first-calf heifers were tested free of antibodies against Bovine viral diarrhea viruses (BVDV) by serum neutralization and free of BVDV by polymerase chain reaction. Twelve were exposed to BVDV-1b strain CA0401186a at 84-86 days of gestation, and 2 were exposed to mock inoculum and served as negative controls. Fetuses were harvested by cesarean section at 115-117 days of gestation. The 12 fetuses removed from the BVDV-exposed heifers were BVDV positive based on virus isolation from kidney, thymus, cerebellum, and spleen. It can be assumed that these fetuses would have developed into persistently infected calves had they been allowed to go to term. Virus was not isolated from the fetuses of control animals. Ear punch samples were collected from all fetuses at time of harvest. Antigen capture enzyme-linked immunosorbent assay (ACE), using a commercial kit, was performed on ear punch samples that were frozen within 5 hr of collection and stored at -20 degrees C until tested, tested after storage for 7 days at room temperature (18-25 degrees C), or tested after storage for 7 days at 37 degrees C. Samples stored for 7 days at room temperature or 37 degrees C lost an average of 34% of their starting weight. All samples from BVDV isolation-positive fetuses tested positive by ACE, whereas samples from nonexposed fetuses tested negative, regardless of storage conditions. These results suggest that ACE testing of skin samples collected from aborted fetuses and stillborn calves found in the field may represent a practical surveillance method for BVDV-induced reproductive disease.

Clinically normal horses developed cellular immunity to Sarcocystis neurona following IM vaccination with a commercial killed S. neurona vaccine, as indicated by the development of measurable anti-S. neurona IgG antibodies and additional intradermal skin testing. Large-scale independent assessments of the vaccine's performance and safety are in progress under field conditions. The next step in the evaluation of this vaccine would be to attempt experimental challenge after a reproducible reliable equine model of S. neurona encephalitis has been established that allows for reisolation of the pathogen after challenge.