Systemic Delivery of a STING Agonist-Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis.

Although stimulator of interferon genes (STING) agonists has shown great promise in preclinical studies, the clinical development of STING agonist therapy is challenged by its limited systemic delivery. Here, positively charged fusogenic liposomes loaded with a STING agonist (PoSTING) are designed for systemic delivery and to preferentially target the tumor microenvironment. When PoSTING is administered intravenously, it selectively targets not only tumor cells but also immune and tumor endothelial cells (ECs). In particular, delivery of STING agonists to tumor ECs normalizes abnormal tumor vasculatures, induces intratumoral STING activation, and elicits robust anti-tumor T cell immunity within the tumor microenvironment. Therefore, PoSTING can be used as a systemic delivery platform to overcome the limitations of using STING agonists in clinical trials.

Gut Microbiome Associating with Carbon and Nitrogen Metabolism during Biodegradation of Polyethene in Tenebrio larvae with Crop Residues as Co-Diets.

Tenebrio molitor and Tenebrio obscurus (Coleoptera: Tenebrionidae) larvae are two commercial insects that eat plant and crop residues as diets and also biodegrade synthetic plastics polyethylene (PE). We examined biodegradation of low-density PE (LDPE) foam (Mn = 28.9 kDa and Mw = 342.0 kDa) with and without respective co-diets, i.e., wheat brain (WB) or corn flour (CF), corn straw (CS), and rice straw (RS) at 4:1 (w/w), and their gut microbiome and genetic metabolic functional groups at 27.0 ± 0.5 °C after 28 days of incubation. The presence of co-diets enhanced LDPE consumption in both larvae and broad-depolymerized the ingested LDPE. The diet type shaped gut microbial diversity, potential pathways, and metabolic functions. The sequence of effectiveness of co-diets was WB or CF > CS > RS for larval development and LDPE degradation. Co-occurrence networks indicated that the larvae co-fed with LDPE displayed more complex correlations of gut microbiome than the larvae fed with single diets. The primary diet of WB or CF and crop residues CS and RS provided energy and nitrogen source to significantly enhance LDPE biodegradation with synergistic activities of the gut microbiota. For the larvae fed LDPE and LDPE plus co-diets, nitrogen fixation function was stimulated compared to normal diets and associated with LDPE biodegradation.

Surface Adaptable and Adhesion Controllable Dry Adhesive with Shape Memory Polymer.

Gecko feet consist of numerous micro/nano hierarchical hairs and exhibit a high adhesion onto various surfaces by van der Waals forces. The gecko, despite its mighty adhesion, can travel efficiently with a rapid adhesion switching due to the end of the hairs on the gecko feet are slanted in one direction. Herein, a shape memory polymer (SMP)-based switchable dry adhesive (SSA), inspired by gecko feet, having tremendous surface adaptability and adhesion switching capability, is reported. The SSA shows not only high adhesion to the various surfaces (≈332.8 kPa) but also easy detachment (nearly 3.73 kPa) due to the characteristic of SMP, which can reversibly recover from a deformed shape to its initial shape. On the basis of the novel adhesion switching property, it is suggested the SSA-applied advanced glass transfer system can lead to feasible application. This experiment confirms that an ultrathin and light glass film is transferred easily and sustainably, and it is believed that the SSA may be a breakthrough and a powerful alternative for not only conventional dry adhesives but also the next-level transfer systems.

Comparison between direct use and PLGA nanocapsules containing drug of traditional Chinese medicine, Tiaojing Zhixue, in treatment of dysfunctional uterine bleeding.

Dysfunctional uterine bleeding is menstrual bleeding in abnormal volume, duration, or time, and it is a common problem in women. A wide range of drug therapies, with varying efficacy, is available for women with dysfunctional uterine bleeding. The use of herbal and traditional medicine is one of the ways to treat this disease, which has fewer side effects than chemical drugs. On the other hand, these medicines have less effect on treatment than chemical drugs. Therefore, increasing their effectiveness in the treatment of diseases has always been important. For this purpose, in this study, a comparison was done between direct use and PLGA nanocapsules containing Tiaojing Zhixue, in the treatment of dysfunctional uterine bleeding. First, PLGA nanocapsules containing Tiaojing Zhixue were synthesized by the electrospray technique. Then 80 women with dysfunctional uterine bleeding were treated with this medicine. These people were divided into two groups of 40 people. The first group was treated with 20mg of Tiaojing Zhixue and the other group was treated with PLGA nanocapsules containing Tiaojing Zhixue for eight months. The duration and frequency of bleeding from one month before the start of treatment and during the eight months after the start of treatment (second, fourth, and eighth month) were assessed in two groups. The two groups were homogeneous in terms of mean frequency of bleeding and mean duration of bleeding before starting treatment. The positive response in the PLGA nanocapsules treatment group (75%) was higher than the direct use drug treatment group (42.5%) (P < 0.01). The rate of side effects was the same in each group. Due to the effectiveness of PLGA nanocapsules in the treatment of dysfunctional uterine bleeding and the lack of side effects, it can be considered as an alternative medicine for the treatment of this disorder.

Automatic Detection of Pearlite Spheroidization Grade of Steel Using Optical Metallography.

To eliminate the effect of subjective factors during manually determining the pearlite spheroidization grade of steel by analysis of optical metallography images, a novel method combining image mining and artificial neural networks (ANN) is proposed. The four co-occurrence matrices of angular second moment, contrast, correlation, and entropy are adopted to objectively characterize the images. ANN is employed to establish a mathematical model between the four co-occurrence matrices and the corresponding spheroidization grade. Three materials used in coal-fired power plants (ASTM A315-B steel, ASTM A335-P12 steel, and ASTM A355-P11 steel) were selected as the samples to test the validity of our proposed method. The results indicate that the accuracies of the calculated spheroidization grades reach 99.05, 95.46, and 93.63%, respectively. Hence, our newly proposed method is adequate for automatically detecting the pearlite spheroidization grade of steel using optical metallography.

Intranasal administration of butorphanol benefits old patients undergoing H-uvulopalatopharyngoplasty: a randomized trial.

BACKGROUND: To evaluate intranasal administration of butorphanol on postoperative pain and early postoperative cognitive dysfunction in old patients undergoing H-uvulopalatopharyngoplasty (H-UPPP). METHODS: A total of 260 male patients (65 to 77 years old) with obstructive sleep apnea hypopnea syndrome and scheduled for H-UPPP were divided randomly to receive intranasal butorphanol, intravenous butorphanol, intranasal fentanyl, or intravenous saline (controls). The definition of preemptive analgesia is that the tested drugs are given before anesthesia induction. Visual analog scale (VAS) and Bruggrmann comfort scale (BCS) scores were recorded at postoperative 1, 6, 12, 18, 24, 36, and 48 h. Postoperative cognitive dysfunction (POCD) was evaluated by Mini-Mental State Examination (MMSE) scores assessed one day before, and 1, 3, and 7 days postsurgery. RESULTS: Compared with control group, those given preemptive analgesia required significantly less sufentanil during surgery, had less pain at postoperative 6-12 h; those given butorphanol experienced less nausea and vomiting, less pain at postoperative 6-24 h, and less POCD. Compared with patients given fentanyl, those given butorphanol required significantly less postoperative fentanyl, had less pain at postoperative 18-24 h, less nausea and vomiting, and less POCD. Compared with patients given intravenous butorphanol, those who received butorphanol by nasal route required significantly less postoperative fentanyl, had less pain at 36 and 48 h, and less POCD. CONCLUSION: Intranasal administration of butorphanol is safe and effective, reducing postoperative usage of analgesics and the incidence of POCD in old patients undergoing H-UPPP. TRIAL REGISTRATION: ChiCTR-TRC-14004121.

Recovery of energy and iron from oily sludge pyrolysis in a fluidized bed reactor.

In the steel industry, about 0.86 ton of oily sludge is produced for every 1000 tons of rolling steel. Due to the adverse impact on human health and the environment, oily sludge is designated as a hazardous waste in the Resource Conservation and Recovery Act (RCRT). In this paper, the pyrolysis treatment of oily sludge is studied in a fluidized bed reactor at a temperature range of 400-600 °C. During oily sludge pyrolysis, a maximum oil yield of 59.2% and a minimum energy loss of 19.0% are achieved at 500 °C. The energy consumption of treating 1 kg oily sludge is only 2.4-2.9 MJ. At the same time, the energy of produced oil, gas and solid residue are 20.8, 6.32, and 0.83 MJ, respectively. In particular, it is found that the solid residue contains more than 42% iron oxide, which can be used as the raw material for iron production. Thus, the simultaneous recovery of energy and iron from oil sludge by pyrolysis is feasible.

Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1ß, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients.

Effects of hypromellose acetate succinate on recrystallization inhibition, miscibility, and dissolution enhancement of baloxavir marboxil solid dispersions.

Solid dispersions (SDs) have emerged as a promising strategy to enhance the solubility and bioavailability of poorly soluble active pharmaceutical ingredients. However, SDs tend to recrystallize unless suitable excipients are utilized. This study aimed to facilitate the rational selection of polymers and formulation design by evaluating the impact of various polymers on the miscibility, and phase behavior of SDs using baloxavir marboxil (BXM) with a high crystallization tendency as a model drug. Meanwhile, the effects of these polymers on the solubility enhancement and recrystallization inhibition were also assessed. The results indicated that the miscibility limit of BXM for HPMCAS was around 40 % drug loading (DL), whereas for PVP, PVPVA, and HPMC approximately 20 % DL. The BXM-HPC system exhibited limited miscibility with DL of 10 % or higher. BXM SDs based on various polymers exhibited varying degrees of spontaneous phase separation once DL exceeded the miscibility limit. Interestingly, a correlation was discovered between the phase separation behavior and the ability of the polymer to inhibit recrystallization. BXM-HPMCAS SDs exhibited optimal dissolution performance, compared with other systems. In conclusion, the physicochemical properties of polymers significantly influence BXM SDs performance and the BXM-HPMCAS SDs might promote an efficient and stable drug delivery system.

Insight into effect of polyethylene microplastic on nitrogen removal in moving bed biofilm reactor: Focusing on microbial community and species interactions.

Microplastics (MPs) pollution has emerged as a global concern, and wastewater treatment plants (WWTPs) are one of the potential sources of MPs in the environment. However, the effect of polyethylene MPs (PE) on nitrogen (N) removal in moving bed biofilm reactor (MBBR) remains unclear. We hypothesized that PE would affect N removal in MBBR by influencing its microbial community. In this study, we investigated the impacts of different PE concentrations (100, 500, and 1000 µg/L) on N removal, enzyme activities, and microbial community in MBBR. Folin-phenol and anthrone colorimetric methods, oxidative stress and enzyme activity tests, and high-throughput sequencing combined with bioinformation analysis were used to decipher the potential mechanisms. The results demonstrated that 1000 µg/L PE had the greatest effect on NH4+-N and TN removal, with a decrease of 33.5 % and 35.2 %, and nitrifying and denitrifying enzyme activities were restrained by 29.5-39.6 % and 24.6-47.4 %. Polysaccharide and protein contents were enhanced by PE, except for 1000 µg/L PE, which decreased protein content by 65.4 mg/g VSS. The positive links of species interactions under 1000 µg/L PE exposure was 52.07 %, higher than under 500 µg/L (51.05 %) and 100 µg/L PE (50.35 %). Relative abundance of some metabolism pathways like carbohydrate metabolism and energy metabolism were restrained by 0.07-0.11 % and 0.27-0.4 %. Moreover, the total abundance of nitrification and denitrification genes both decreased under PE exposure. Overall, PE reduced N removal by affecting microbial community structure and species interactions, inhibiting some key metabolic pathways, and suppressing key enzyme activity and functional gene abundance. This paper provides new insights into assessing the risk of MPs to WWTPs, contributing to ensuring the health of aquatic ecosystems.

Microplastics shaped performance, microbial ecology and community assembly in simultaneous nitrification, denitrification and phosphorus removal process.

The widespread use of microplastics (MPs) has led to an increase in their discharge to wastewater treatment plants. However, the knowledge of impact of MPs on macro-performance and micro-ecology in simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) systems is limited, hampering the understanding of potential risks posed by MPs. This study firstly comprehensively investigated the performance, species interactions, and community assembly under polystyrene (PS) and polyvinyl chloride (PVC) exposure in SNDPR systems. The results showed under PS (1, 10 mg/L) and PVC (1, 10 mg/L) exposure, total nitrogen removal was reduced by 3.38-10.15 %. PS and PVC restrained the specific rates of nitrite and nitrate reduction (SNIRR, SNRR), as well as the activities of nitrite and nitrate reductase enzymes (NIR, NR). The specific ammonia oxidation rate (SAOR) and activity of ammonia oxidase enzyme (AMO) were reduced only at 10 mg/L PVC. PS and PVC enhanced the size of co-occurrence networks, niche breadth, and number of key species while decreasing microbial cooperation by 5.85-13.48 %. Heterogeneous selection dominated microbial community assembly, and PS and PVC strengthened the contribution of stochastic processes. PICRUSt prediction further revealed some important pathways were blocked by PS and PVC. Together, the reduced TN removal under PS and PVC exposure can be attributed to the inhibition of SAOR, SNRR, and SNIRR, the restrained activities of NIR, NR, and AMO, the changes in species interactions and community assembly mechanisms, and the suppression of some essential metabolic pathways. This paper offers a new perspective on comprehending the effects of MPs on SNDPR systems.

Parallel on-axis phase-shifting holographic phase microscopy based on reflective point-diffraction interferometer with long-term stability.

Parallel on-axis two-step phase-shifting reflective point-diffraction interferometry for holographic phase microscopy based on Michelson architecture is proposed. A cube beamsplitter splits the object wave into two copies within the two arms. The reference wave is rebuilt by low-pass filtering with a pinhole-masked mirror. Both object and reference waves are split into two beams by a grating in a 4f imaging system; thus, two interferograms with quadrature phase-shift can be acquired simultaneously with the aid of polarization elements. The approach has the merit of nanometers-scale phase stability over hours due to its quasi-common-path geometry. It can make full use of camera spatial bandwidth while its temporal resolution is as fast as the camera frame rate. Phase imaging on microscale specimen is implemented, and the experimental results demonstrate that the proposed approach is suitable for investigating dynamic processes.

Effect of a Mismatched Vaccine against the Outbreak of a Novel FMD Strain in a Pig Population.

In December 2014, a novel foot and mouth disease (FMD) virus was introduced to a pig farm in South Korea, despite the animals being vaccinated. A marginal antigenic matching between the novel and vaccine strains potentially led to the infection of the vaccinated animals. To understand the impact of using an FMD vaccine on the transmission dynamics of an unmatched field strain, simulation models were employed using daily reported data on clinical cases from the farm. The results of this study indicated that immunisation with the FMD vaccine reduced the shedding of the novel FMD virus in pigs. However, there was no evidence to suggest that the immunisation had a significant effect in reducing the development of clinical signs. These findings highlight that the use of an unmatched FMD vaccine can confound the outbreak by altering the disease dynamics of the novel virus. Based on this study, we emphasise the importance of continuous testing to ensure antigenic matching between the circulating strains and the vaccine pool.

Changes in the intestinal microbiota of children with hand, foot, and mouth disease under 3 years old.

This study aimed to clarify the characteristics of intestinal microbiota in children with hand, foot, and mouth disease (HFMD) under 3 years old. Fresh feces were collected from 54 children with HFMD and 30 healthy children. All of them were <3 years old. Sequencing of the 16S rDNA amplicons was performed. Between the 2 groups, the richness, diversity, and structure of the intestinal microbiota were analyzed by α-diversity and ß-diversity. Linear discriminant analysis and LEfSe analyses were used to compare different bacterial classifications. The sex and age of the children in the 2 groups were not statistically significant (P = .92 and P = .98, respectively). Compared to healthy children, the Shannon index, Ace index, and Chao index were lower in children with HFMD (P = .027, P = .012, and P = .012, respectively). Based on the weighted or unweighted UniFrac distance analysis, the structure of the intestinal microbiota in HFMD was also significantly changed (P = .002 and P < .001, respectively). Linear discriminant analysis and LEfSe analysis showed that the changes of key bacteria were manifested as a decrease in Prevotella and Clostridium_XIVa (P < .001 and P < .001, respectively), while Escherichia and Bifidobacterium increased (P = .025 and P = .001, respectively). Children with HFMD under 3 years of age have intestinal microbiota disorder and show a decrease in diversity and richness. The decrease in the abundance of Prevotella and Clostridium, which can produce short-chain fatty acids, is also one of the characteristics of the change. These results can offer a theoretical foundation for the pathogenesis and microecological treatment of HFMD in infants.

Microplastics perturb nitrogen removal, microbial community and metabolism mechanism in biofilm system.

Microplastics (MPs) are a significant component of global pollution and cause widespread concern, particularly in wastewater treatment plants. While understanding the impact of MPs on nutrient removal and potential metabolism in biofilm systems is limited. This work investigated the impact of polystyrene (PS) and polyethylene terephthalate (PET) on the performance of biofilm systems. The results revealed that at concentrations of 100 and 1000 µg/L, both PS and PET had almost no effect on the removal of ammonia nitrogen, phosphorus, and chemical oxygen demand, but reduced the removal of total nitrogen by 7.40-16.6%. PS and PET caused cell and membrane damage, as evidenced by increases in reactive oxygen species and lactate dehydrogenase to 136-355% and 144-207% of the control group. Besides, metagenomic analysis demonstrated both PS and PET changed the microbial structure and caused functional differences. Some important genes in nitrite oxidation (e.g. nxrA), denitrification (e.g. narB, nirABD, norB, and nosZ), and electron production process (e.g. mqo, sdh, and mdh) were restrained, meanwhile, species contribution to nitrogen-conversion genes was altered, therefore disturbing nitrogen-conversion metabolism. This work contributes to evaluating the potential risks of biofilm systems exposed to PS and PET, maintaining high nitrogen removal and system stability.

Recent advances towards micro(nano)plastics research in wetland ecosystems: A systematic review on sources, removal, and ecological impacts.

In recent years, microplastics/nanoplastics (MPs/NPs) have received substantial attention worldwide owing to their wide applications, persistence, and potential risks. Wetland systems are considered to be an important "sink" for MPs/NPs, which can have potential ecological and environmental effects on the ecosystem. This paper provides a comprehensive and systematic review of the sources and characteristics of MPs/NPs in wetland ecosystems, together with a detailed analysis of MP/NP removal and associated mechanisms in wetland systems. In addition, the eco-toxicological effects of MPs/NPs in wetland ecosystems, including plant, animal, and microbial responses, were reviewed with a focus on changes in the microbial community relevant to pollutant removal. The effects of MPs/NPs exposure on conventional pollutant removal by wetland systems and their greenhouse gas emissions are also discussed. Finally, current knowledge gaps and future recommendations are presented, including the ecological impact of exposure to various MPs/NPs on wetland ecosystems and the ecological risks of MPs/NPs associated with the migration of different contaminants and antibiotic resistance genes. This work will facilitate a better understanding of the sources, characteristics, and environmental and ecological impacts of MPs/NPs in wetland ecosystems, and provide a new perspective to promote development in this field.

Sodium Phytate-Incorporated Gelatin-Silicate Nanoplatelet Composites for Enhanced Cohesion and Hemostatic Function of Shear-Thinning Biomaterials.

Shear-thinning biomaterials (STBs) based on gelatin-silicate nanoplatelets (SNs) are emerging as an alternative to conventional coiling and clipping techniques in the treatment of vascular anomalies. Improvements in the cohesion of STB hydrogels pave the way toward their translational application in minimally invasive therapies such as endovascular embolization repair. In the present study, sodium phytate (Phyt) additives are used to tune the electrostatic network of SNs-gelatin STBs, thereby promoting their mechanical integrity and facilitating injectability through standard catheters. We show that an optimized amount of Phyt enhances storage modulus by approximately one order of magnitude and reduces injection force by ≈58% without compromising biocompatibility and hydrogel wet stability. The Phyt additives are found to decrease the immune responses induced by SNs. In vitro embolization experiments suggest a significantly lower rate of failure in Phyt-incorporated STBs than in control groups. Furthermore, the addition of Phyt leads to accelerated blood coagulation (reduces clotting time by ≈45% compared to controls) due to the contributions of negatively charged phosphate groups, which aid in the prolonged durability of STB in coagulopathic patients. Therefore, the proposed approach is an effective method for the design of robust and injectable STBs for minimally invasive treatment of vascular malformations.

Aerogel-Based Biomaterials for Biomedical Applications: From Fabrication Methods to Disease-Targeting Applications.

Aerogel-based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol-gel, aging, drying, and self-assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic-based technologies and 3D printing can be combined with aerogel-based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel-based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.

Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1-null mice.

Cleft palate represents one of the most common congenital birth defects in human. During embryonic development, palatal shelves display oronasal (O-N) and anteroposterior polarity before the onset of fusion, but how the O-N pattern is established and how it relates to the expansion and fusion of the palatal shelves are unknown. Here we address these questions and show that O-N patterning is associated with the expansion and fusion of the palatal shelves and that Dlx5 is required for the O-N patterning of palatal mesenchyme. Loss of Dlx5 results in downregulation of Fgf7 and expanded Shh expression from the oral to the nasal side of the palatal shelf. This expanded Shh signaling is sufficient to restore palatal expansion and fusion in mice with compromised palatal mesenchymal cell proliferation, such as Msx1-null mutants. Exogenous Fgf7 inhibits Shh signaling and reverses the cranial neural crest (CNC) cell proliferation rescue in the Msx1/Dlx5 double knockout palatal mesenchyme. Thus, Dlx5-regulated Fgf7 signaling inhibits the expression of Shh, which in turn controls the fate of CNC cells through tissue-tissue interaction and plays a crucial role during palatogenesis. Our study shows that modulation of Shh signaling may be useful as a potential therapeutic approach for rescuing cleft palate.

Impact of risk-based partial vaccination on clinical incidence and seroprevalence of foot and mouth disease in Lao PDR.

Foot and mouth disease (FMD) is endemic in the Lao People's Democratic Republic (PDR) and it causes economic loss to smallholder husbandry systems. An intervention programme based on a risk-based partial vaccination strategy was implemented in three provinces of Lao PDR (Champasak, Savannakhet and Xiangkhouang) to immunise domestic cattle and buffalo during 2016-2020. Two cross-sectional surveys were conducted in 2016/17 and 2020 to evaluate the impact of the vaccination programme on the prevalence of FMD virus exposure and clinical incidence of the disease. A total of 212 villages were visited during the two surveys, collecting 1609 household-level questionnaire results and 5931 blood samples of domestic cattle and buffalo. Blood samples were tested for the presence of antibodies to the non-structural proteins of FMD virus, and seroprevalence of 42.5 and 47.5% in 2016/17 and 2020, respectively were found. Multivariable regression analysis indicated that the efficacy of the FMD vaccination programme for reducing FMD virus circulation varied by province. In general, the incidence of clinical FMD increased toward the end of the 5-year intervention period, coinciding with a reduction of vaccine coverage in the last 2 years of the period. The findings suggest that the risk-based vaccination strategy achieved a marginally protective effect against the circulation of FMD virus with the possible limiting factors being operational constraints of public veterinary services, lack of farmers' compliance and unsustainable funding. We conclude that consistent resource availability and higher vaccination coverage is required to successfully control FMD with a risk-based vaccination strategy in Lao PDR.