Use of Free Internal Mammary Artery Perforator Flap Harvested With Minimally Invasive Approach for Facial Reconstruction: Report of Two Cases.

The internal mammary artery perforator (IMAP) flap has been widely used for chest wall and neck reconstruction. The color of its skin paddle closely resembles that of facial skin, making it attractive for facial reconstruction. However, there has been insufficient investigations reporting the use of free IMAP flap. Furthermore, even in such studies, somewhat invasive procedures, including rib cartilage resection, were employed to ensure sufficient pedicle length, potentially increasing donor morbidity. Our report presents two cases of successful facial defect reconstruction using a free IMAP flap harvested with minimal donor site damage, showing its feasibility. In the first case, a 48-year-old male underwent wide excision for a malignant melanoma on his right cheek, resulting in a 4 × 4.5 cm full-thickness defect. A free IMAP flap with a 2.5 cm pedicle, was harvested without rib cartilage resection, preserving IMA main trunk, and transferred with anastomosed to the angular vessels within the defect. The second patient presented with a 4.5 × 3.5 cm basal cell carcinoma on the left cheek, necessitating wide excision and leaving a 6 × 5 cm defect. A free IMAP flap was harvested with the same approach and successfully reconstructed the defect with connected to the superficial temporal vessels using vascular bridge. Both patients were discharged complication-free, with no recurrence during 24 and 15 months of follow-up, respectively. They were highly satisfied with the final skin color and texture outcomes. Harvesting a free IMAP flap while minimizing donor morbidity may offer an attractive option for facial reconstruction.

Chalcone-based benzenesulfonamides as potent and selective inhibitors for human carbonic anhydrase II: Design, synthesis, in vitro, and in silico studies.

Sulfonamides are promising classical carbonic anhydrase (CA; EC 4.2.1.1) inhibitors, being used for several medical purposes such as diuretics, anticonvulsants, topically acting antiglaucoma agents, for antiobesity and anticancer therapies. Herein, a series of chalcone-based benzenesulfonamides (3a‒m) was synthesized and assessed for its inhibitory activity against a panel of four human carbonic anhydrases (hCA isoforms I, II, IX, and XII). Most compounds displayed single- to double-digit nanomolar inhibition constants (Kis), with some derivatives being more potent and/or selective than the standard drug acetazolamide (AAZ). Among the synthesized compounds, 3g compound demonstrated the highest inhibitory activity against the hCA II isoform (Ki = 2.5 nM) with 30-, 9-, and 11-fold selectivity for hCA II over the I, IX, and XII isoforms, respectively. Structure-activity relationships for different substitution patterns were analyzed. Additionally, a molecular docking study showed that compound 3g bound to hCA II by coordinating with the zinc ion through the deprotonated benzenesulfonamide moiety, in addition to a hydrogen bond formed between an oxygen of the sulfonamide moiety and Thr199. Moreover, the chalcone core participated in van der Waals interactions with some active site residues, such as Ile91, Val121, and Leu198. Consequently, this report introduces a successful approach toward identifying compound 3g as a highly potent and selective chalcone-based benzenesulfonamide inhibitor of hCA II worthy of further investigation.

Alantolactone alleviates epithelial-mesenchymal transition by regulating the TGF-ß/STAT3 signaling pathway in renal fibrosis.

Objective: The epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) plays a crucial role in renal interstitial fibrosis and inflammation, which are key components of chronic kidney disease (CKD). Alantolactone, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), is used in Chinese herbal medicine. Despite its use, the effects of alnatolactone on EMT of RTECs has not been fully elucidated. Methods: In this study, we investigated the potential of alantolactone to EMT in vivo and in vitro. Our experiments were performed using a unilateral ureteral obstruction (UUO) models and HK-2 cells, RTECs, treated with transforming growth factor (TGF-ß). Results: Alantolactone decreased tubular injury and reduced the expression of vimentin, a key EMT marker, while increasing E-cadherin expression in UUO kidneys. Similarly, in RTECs, alantolactone inhibited TGF-ß-induced EMT and its markers. Furthermore, alantolactone attenuated UUO- and TGF-ß-induced STAT3 phosphorylation both in vivo and in vitro, and inhibited the expression of TWIST, an EMT transcription factor, in both models. Conclusion: Alantolactone improves EMT in RTECs by inhibiting STAT3 phosphorylation and Twist expression, suggesting its potential as a therapeutic agent for kidney fibrosis.

Chemical induction of the interaction between AIMP2-DX2 and Siah1 to enhance ubiquitination.

AIMP2-DX2 (hereafter DX2) is an oncogenic variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2) that mediates tumorigenic interactions with various factors involved in cancer. Reducing the levels of DX2 can effectively inhibit tumorigenesis. We previously reported that DX2 can be degraded through Siah1-mediated ubiquitination. In this study, we identified a compound, SDL01, which enhanced the interaction between DX2 and Siah1, thereby facilitating the ubiquitin-dependent degradation of DX2. SDL01 was found to bind to the pocket surrounding the N-terminal flexible region and GST domain of DX2, causing a conformational change that stabilized its interaction with Siah1. Our findings demonstrate that protein-protein interactions (PPIs) can be modulated through chemically induced conformational changes.

Identification of Cellular Isoschaftoside-Mediated Anti-Senescence Mechanism in RAC2 and LINC00294.

As cellular senescence, reactive oxygen species (ROS) accumulate excessively, causing cellular damage. Flavonoids derived from natural products are known for their antioxidant effects and their ability to delay cellular senescence. Previous studies have attempted to mitigate cellular senescence using flavonoids from natural sources. However, the detailed mechanisms and regulatory targets of some flavonoids exhibiting antioxidant effects have not been fully elucidated. Therefore, we screened a library of flavonoids for antioxidant properties. Isoschaftoside, a glycosidic flavonoid, significantly reduced ROS levels in senescent cells. It was found that mitochondrial function was restored, and dependence on glycolysis was reduced in senescent cells treated with isoschaftoside. Additionally, we identified that isoschaftoside suppresses ROS by reducing the expression of RAC2 and LINC00294 in senescent cells. Taken together, this study establishes a novel mechanism for ROS inhibition and the regulation of cellular senescence by isoschaftoside. Our findings contribute important insights to antioxidant and anti-senescence research.

Structural and biochemical investigation into stable FGF2 mutants with novel mutation sites and hydrophobic replacements for surface-exposed cysteines.

Fibroblast growth factor 2 (FGF2) is an attractive biomaterial for pharmaceuticals and functional cosmetics. To improve the thermo-stability of FGF2, we designed two mutants harboring four-point mutations: FGF2-M1 (D28E/C78L/C96I/S137P) and FGF2-M2 (D28E/C78I/C96I/S137P) through bioinformatics, molecular thermodynamics, and molecular modeling. The D28E mutation reduced fragmentation of the FGF2 wild type during preparation, and the substitution of a whale-specific amino acid, S137P, enhanced the thermal stability of FGF2. Surface-exposed cysteines that participate in oligomerization through intermolecular disulfide bond formation were substituted with hydrophobic residues (C78L/C78I and C96I) using the in silico method. High-resolution crystal structures revealed at the atomic level that the introduction of mutations stabilizes each local region by forming more favorable interactions with neighboring residues. In particular, P137 forms CH-π interactions with the side chain indole ring of W123, which seems to stabilize a ß-hairpin structure, containing a heparin-binding site of FGF2. Compared to the wild type, both FGF2-M1 and FGF2-M2 maintained greater solubility after a week at 45 °C, with their Tm values rising by ~ 5 °C. Furthermore, the duration for FGF2-M1 and FGF2-M2 to reach 50% residual activity at 45 °C extended to 8.8- and 8.2-fold longer, respectively, than that of the wild type. Interestingly, the hydrophobic substitution of surface-exposed cysteine in both FGF2 mutants makes them more resistant to proteolytic cleavage by trypsin, subtilisin, proteinase K, and actinase than the wild type and the Cys → Ser substitution. The hydrophobic replacements can influence protease resistance as well as oligomerization and thermal stability. It is notable that hydrophobic substitutions of surface-exposed cysteines, as well as D28E and S137P of the FGF2 mutants, were designed through various approaches with structural implications. Therefore, the engineering strategies and structural insights adopted in this study could be applied to improve the stability of other proteins.

Short- and medium-term exposure to ambient air pollution and periodontal status.

We investigated the association between ambient air pollutant exposure and periodontal health using data from 17,271 adults in the Korea National Health and Nutrition Examination Survey (2012-2015). Participants' periodontal status was categorized based on their community periodontal index (CPI) scores. Using multiple logistic regression models, we examined the relationship between air pollutant levels and poor periodontal status at various lag periods. After adjusting for potential confounders, PM10 exposure was associated with a poor periodontal status (short-term: 0-1 and 0-2 lag days; medium-term: 0-1 and 0-2 lag months). SO2 exposure showed similar associations (short-term, 0-2 to 0-7 lag days; medium-term, 0-4 to 0-6 lag months). Only increased medium-term O3 exposure (0-2 to 0-6 lag months) was associated with a poor periodontal status. NO2 exposure was inversely associated with poor periodontal status for both short- and medium-term durations.

Identification of High Linoleic Acid Varieties in Tetraploid Perilla Through Gamma-ray Irradiation and CRISPR/Cas9.

Perilla (Perilla frutescens (L.) var frutescens) is a traditional oil crop in Asia, recognized for its seeds abundant in α-linolenic acid (18:3), a key omega-3 fatty acid known for its health benefits. Despite the known nutritional value, the reason behind the higher 18:3 content in tetraploid perilla seeds remained unexplored. Gamma irradiation yielded mutants with altered seed fatty acid composition. Among the mutants, DY-46-5 showed a 27% increase in 18:2 due to the 4 bp deletion of PfrFAD3b and NC-65-12 displayed a 16% increase in 18:2 due to the loss of function of PfrFAD3a through a large deletion. Simultaneous knockout of two copies of FATTY ACID DESATURASE 3 (PfrFAD3a and PfrFAD3b) using CRISPR/Cas9 resulted in an increase in 18:2 by up to 75% and a decrease in 18:3 to as low as 0.3% in seeds, emphasizing the pivotal roles of both genes in 18:3 synthesis in tetraploid perilla. Furthermore, diploid Perilla citriodora, the progenitor of cultivated tetraploid perilla, harbors only PfrFAD3b, with fatty acid analysis revealing lower 18:3 levels than tetraploid perilla. In conclusion, the enhanced 18:3 content in cultivated tetraploid perilla seeds can be attributed to the acquisition of two FAD3 copies through hybridization with wild-type diploid perilla.

High production of recombinant protein using geminivirus-based deconstructed vectors in Nicotiana benthamiana.

We focused on the geminiviral vector systems to develop an efficient vector system for plant biotechnology. Begomoviruses and curtoviruses, which belong to the Geminiviridae family, contain an intergenic region (IR) and four genes involved in replication, including replication-associated protein (Rep, C1), transcriptional activator (TrAP, C2), and replication enhancer (REn, C3). Geminiviruses can amplify thousands of copies of viral DNA using plant DNA polymerase and viral replication-related enzymes and accumulate viral proteins at high concentrations. In this study, we optimized geminiviral DNA replicon vectors based on tomato yellow leaf curl virus (TYLCV), honeysuckle yellow vein virus (HYVV), and mild curly top virus (BMCTV) for the rapid, high-yield plant-based production of recombinant proteins. Confirmation of the optimal combination by co-delivery of each replication-related gene and each IR harboring the Pontellina plumata-derived turbo green fluorescence protein (tGFP) gene via agroinfiltration in Nicotiana benthamiana leaves resulted in efficient replicon amplification and robust protein production within 3 days. Co-expression with the p19 protein of the tomato bush stunt virus, a gene-silencing suppressor, further enhanced tGFP accumulation by stabilizing mRNA. With this system, tGFP protein was produced at 0.7-1.2 mg/g leaf fresh weight, corresponding to 6.9-12.1% in total soluble protein. These results demonstrate the advantages of rapid and high-level production of recombinant proteins using the geminiviral DNA replicon system for transient expression in plants.

Hybrid CMOS-Memristor synapse circuits for implementing Ca ion-based plasticity model.

Neuromorphic computing research is being actively pursued to address the challenges posed by the need for energy-efficient processing of big data. One of the promising approaches to tackle the challenges is the hardware implementation of spiking neural networks (SNNs) with bio-plausible learning rules. Numerous research works have been done to implement the SNN hardware with different synaptic plasticity rules to emulate human brain operations. While a standard spike-timing-dependent-plasticity (STDP) rule is emulated in many SNN hardware, the various STDP rules found in the biological brain have rarely been implemented in hardware. This study proposes a CMOS-memristor hybrid synapse circuit for the hardware implementation of a Ca ion-based plasticity model to emulate the various STDP curves. The memristor was adopted as a memory device in the CMOS synapse circuit because memristors have been identified as promising candidates for analog non-volatile memory devices in terms of energy efficiency and scalability. The circuit design was divided into four sub-blocks based on biological behavior, exploiting the non-volatile and analog state properties of memristors. The circuit was designed to vary weights using an H-bridge circuit structure and PWM modulation. The various STDP curves have been emulated in one CMOS-memristor hybrid circuit, and furthermore a simple neural network operation was demonstrated for associative learning such as Pavlovian conditioning. The proposed circuit is expected to facilitate large-scale operations for neuromorphic computing through its scale-up.

Safety of performing multiple free flap surgeries by a single surgeon in a single day.

BACKGROUND: With the growing popularity of the use of free flaps, surgeons may frequently encounter situations necessitating the performance of multiple free flap surgeries in a single day. Given its prolonged duration and technical complexity, concerns remain regarding their safety. This study investigated whether a single surgeon conducting multiple free flap surgeries in a day heightens the risk of complications. METHODS: Patients who underwent free flap-based reconstruction from March 2002 to May 2023 were reviewed and categorized into 3 groups: one flap per day (Group 1), multiple flaps per day on the same patient (Group 2), and multiple flaps per day on different patients (Group 3). Outcomes, particularly perfusion-related complications (PRCs), were compared. RESULTS: In total, 1910 cases were analyzed: 1570 in Group 1, 126 in Group 2, and 214 in Group 3. Over time, the proportion of cases in Group 3 increased. Group 3 had fewer breast reconstruction cases but more lower extremity reconstructions, with a higher prevalence of chronic wounds. Although the rates of PRCs varied among groups, multivariable analysis exhibited no association of performing multiple flaps in a day with their occurrence, regardless of breast or nonbreast reconstruction. The rate of arterial insufficiency was significantly higher in group 3 compared with group 1 after adjusting for other variables. CONCLUSIONS: Performing multiple free flaps in a single day may not significantly increase the risks of overall PRCs. However, there appears to be a higher incidence of arterial insufficiency, emphasizing the need for careful planning and precise execution of procedures.

Learning curve analysis for hand-assisted laparoscopic living donor nephrectomy: an analysis of 96 consecutive cases performed by a trained gastrointestinal surgeon.

Purpose: This study aims to analyze the learning curve of hand-assisted laparoscopic living donor nephrectomy (HLDN) conducted by a trained gastrointestinal surgeon. Methods: A retrospective analysis was performed on the perioperative clinical data of 96 consecutive patients who underwent HLDN from May 2013 to March 2023. The learning curve was evaluated using the cumulative sum (CUSUM) test based on operation time and risk-adjusted CUSUM for postoperative complications. Patients were divided into three groups (novice, development, and competency phases) based on changes in operation time. Patient demographics and perioperative outcomes were compared between each group. Results: Among the patients, 35 were male, with a mean age of 48.9 ± 11.3 years and a mean body mass index (BMI) of 24.5 ± 3.2 kg/m2. The novice phase (phase 1) included the first 30 cases, with the development phase (phase 2) up to the 65th case. Operation times were significantly different across phases, averaging 263.2 ± 33.4, 211.1 ± 34.4, and 161.1 ± 31.3 minutes for phases 1, 2, and 3, respectively (P < 0.001). Blood loss decreased gradually across phases (phase 1, 264.7 ± 144.4 mL; phase 2, 239.7 ± 166.3 mL; phase 3, 198.8 ± 103.5 mL), though not statistically significant. BMI impacted operation time only in phase 1. Overall postoperative complications occurred in 13 cases (Clavien-Dindo grade I, 4 cases; grade II, 9 cases), with no significant differences across phases. Conclusion: HLDN can be safely performed by a trained gastrointestinal surgeon, with approximately 30 cases needed to achieve proficiency.

Learning curve for robot-assisted nipple-sparing mastectomy: A single institution experience.

BACKGROUND: Robot-assisted nipple sparing mastectomy (RANSM) is emerging because it offers hidden incisions and ergonomic movements. In this study, we report the learning curve and feasibility of RANSM. METHODS: A retrospective study was conducted among women who underwent RANSM with immediate breast reconstruction from July 2019 to June 2022. All RANSM procedures were performed by a single surgeon. We divided all the cases into two phases: the early phase (cases 1 to 21) and the late phase (cases 22 to 46). The total operation time, breast operation time, docking time, and console time were analyzed, and the cumulative sum (CUSUM) method was used to evaluate the effects of case experience accumulation on the time required for RANSM. Postoperative complications were analyzed according to their Clavien-Dindo grade. RESULTS: Overall, 42 women underwent 46 RANSM procedures. In the early and late phases, the mean console times were 78.1 min and 60.1 min (p = 0.011), respectively. In learning curve analysis, 21 RANSM procedures were required to reduce the breast operation time. Two cases of Clavien-Dindo grade III postoperative complications occurred (4.3 %). One case was an implant removal caused by infection, and the other was partial nipple ischemia; both occurred in the early phase, with none in the late phase. CONCLUSIONS: The breast operation time improved after the 21st RANSM procedure, and only two cases had Clavien-Dindo grade III or higher postoperative complications. RANSM is thus technically feasible and acceptable, with a short learning curve.

A novel chemically engineered multifunctional statin conjugate as self-assembled nanoparticles inhibiting bile acid transporters.

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.

From pixels to druggable leads: A CADD strategy for the design and synthesis of potent DDR1 inhibitors.

BACKGROUND AND OBJECTIVE: While numerous in silico tools exist for target-based drug discovery, the inconsistent integration of in vitro data with predictive models hinders research and development productivity. This is particularly apparent during the Hit-to-Lead stage, where unreliable in-silico tools often lead to suboptimal lead selection. Herein, we address this challenge by presenting a CADD-guided pipeline that successfully integrates rational drug design with in-silico hits to identify a promising DDR1 lead. METHODS: 2 × 1000 ns MD simulations along with their respective FEL and MMPBSA analyses were employed to guide the rational design and synthesis of 12 novel compounds which were evaluated for their DDR inhibition. RESULTS: The molecular dynamics investigation of the initial hit led to the identification of key structural features within the DDR1 binding pocket. The identified key features were used to guide the rational design and synthesis of twelve novel derivatives. SAR analysis, biological evaluation, molecular dynamics, and free energy calculations were carried out for the synthesized derivatives to understand their mechanism of action. Compound 4c exhibited the strongest inhibition and selectivity for DDR1, with an IC50 of 0.11 µM. CONCLUSIONS: The MD simulations led to the identification of a key hydrophobic groove in the DDR1 binding pocket. The integrated approach of SAR analysis with molecular dynamics led to the identification of compound 4c as a promising lead for further development of potent and selective DDR1 inhibitors. Moreover, this work establishes a protocol for translating in silico hits to real world bioactive druggable leads.

Functional Characterization of the Effects of CsDGAT1 and CsDGAT2 on Fatty Acid Composition in Camelina sativa.

Triacylglycerols (TAGs) are the storage oils of plant seeds, and these lipids provide energy for seed germination and valuable oils for human consumption. Three diacylglycerol acyltransferases (DGAT1, DGAT2, and DGAT3) and phospholipid:diacylglycerol acyltransferases participate in the biosynthesis of TAGs. DGAT1 and DGAT2 participate in the biosynthesis of TAGs through the endoplasmic reticulum (ER) pathway. In this study, we functionally characterized CsDGAT1 and CsDGAT2 from camelina (Camelina sativa). Green fluorescent protein-fused CsDGAT1 and CsDGAT2 localized to the ER when transiently expressed in Nicotiana benthamiana leaves. To generate Csdgat1 and Csdgat2 mutants using the CRISPR/Cas9 system, camelina was transformed with a binary vector carrying Cas9 and the respective guide RNAs targeting CsDGAT1s and CsDGAT2s via the Agrobacterium-mediated floral dip method. The EDD1 lines had missense and nonsense mutations in the CsDGAT1 homoeologs, suggesting that they retained some CsDGAT1 function, and their seeds showed decreased eicosaenoic acid (C20:1) contents and increased C18:3 contents compared to the wild type (WT). The EDD2 lines had a complete knockout of all CsDGAT2 homoeologs and a slightly decreased C18:3 content compared to the WT. In conclusion, CsDGAT1 and CsDGAT2 have a small influence on the seed oil content and have an acyl preference for C20:1 and C18:3, respectively. This finding can be applied to develop oilseed plants containing high omega-3 fatty acids or high oleic acid.

Interactions of bosutinib with drug transporters: In vitro and In vivo inhibition of organic cation transporter 2, multidrug and toxin extrusion protein 1, and breast cancer resistance protein by bosutinib.

Bosutinib has been approved for use in patients with chronic myeloid leukemia. Information regarding the effects of bosutinib on clinically important drug transporters is limited, particularly regarding its inhibitory potency on transporters and in vivo effects. Therefore, we conducted a study investigating the in vitro and in vivo effects of bosutinib on drug transporters. Bosutinib showed moderate or strong inhibitory effects on organic cation transporter 2, multidrug and toxin extrusion protein 1, and breast cancer resistance protein with IC50 values of 0.0894, 0.598, and 10.8 µM, respectively. In vivo experiments in rats showed that bosutinib significantly inhibited organic cation transporter 2 and multidrug and toxin extrusion protein 1, leading to a marked reduction in the renal clearance of metformin and an increase in systemic exposure to metformin. Bosutinib increased systemic exposure to sulfasalazine, a probe substrate of breast cancer resistance protein, by 75 % in rats, highlighting its potential to significantly affect intestinal drug efflux. These quantitative changes suggest that bosutinib may alter the in vivo pharmacokinetics of drugs that are substrates of these transporters, potentially leading to increased drug exposure and enhanced or unexpected pharmacological effects.

Quantification of methane and carbon dioxide surface emissions from a metropolitan landfill based on quasi-continuous eddy covariance measurement.

The Sudokwon landfill (SL) in the Seoul metropolitan area, South Korea, is among the world's largest landfills, striving to curtail landfill gas (LFG) emissions and achieve carbon neutrality by 2050. Since 2005, the SL Management Corporation (SLC) has measured LFG emissions (i.e., methane (CH4) and carbon dioxide (CO2)) using a dynamic flux chamber proposed by the US EPA. However, uncertainty prevails in validating the reduction of LFG emissions due to the limited spatiotemporal data coverage. In 2020, an eddy covariance (EC) system was installed to enhance measurements, revealing highly fluctuating LFG emissions driven by waste layer LFG production, LFG collection, and atmospheric pressure changes. During the study period, the annual CH4 emission increased slightly from 465.0 ± 4.2 to 485.5 ± 6.4 g C m-2, while that of CO2 decreased by 2/3 (from 408.7 ± 16.5 to 270.6 ± 18.8 g C m-2), primarily due to the doubled CO2 uptake by the vegetated topsoil. Our first long-term (March 2020 to February 2022) quasi-continuous monitoring using EC (with a gap-filling and partitioning technique based on Random Forest) emphasizes the difficulty of temporal upscaling of discontinuously observed surface emissions to quantify the LFG inventory and the need for continuous observations or suitable proxies (e.g., atmospheric CH4 concentration).

The Fumigation Toxicity of Three Benzoate Compounds against Phosphine-Susceptible and Phosphine-Resistant Strains of Rhyzopertha dominica and Sitophilus oryzae.

Phosphine (PH3) has been widely used as a fumigant in food storage, but increasing PH3 resistance in major pests makes finding alternative fumigants urgent. Methyl benzoate (MBe), a volatile organic compound regarded to be a food-safe natural product, has recently demonstrated significant toxicity against a variety of insect pests. This study is the first evaluation of the fumigation toxicity of three benzoate compounds, MBe, vinyl benzoate, and ethyl benzoate, against PH3-susceptible and PH3-resistant strains of Rhyzopertha dominica and Sitophilus oryzae. All strains were exposed to the compounds at concentrations up to 20 µL/1.5 L air for 24 h. Compared to vinyl benzoate and ethyl benzoate, MBe induced higher mortality rates in all strains at all concentrations. When food was made available, the lethal median concentration for MBe was 10-17-fold higher than when tested without food. Moreover, no significant differences were observed between the responses of the PH3-susceptible and PH3-resistant strains to the compounds. Notably, S. oryzae was more susceptible to MBe. In laboratory settings, MBe successfully controlled PH3-resistant strains of R. dominica and S. oryzae, making it a viable option for PH3-resistance management. Thus, MBe might be suitable for food security programs as an environmentally benign alternative fumigant.