Search

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π–π interaction to prepare g–C3N4–loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt–N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g–C3N4–loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage in vitro and an OA joint model in vivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

Background: Acute pancreatitis in pregnancy (APIP) is a rare but life-threatening complication for both mother and fetus. The purpose of this study was to describe the etiology, clinical indices, early predictive markers and maternal fetal outcomes of APIP. Methods: We retrospectively reviewed 52 APIP cases treated at the 5 tertiary care centers from January 2017 to December 2021 in Guangdong, China. We analyzed the etiology, vital signs, laboratory indices, predictive markers and long-term outcomes of APIP. Results: The most common causes of APIP were hypertriglyceridemia (36.5%) and biliary disease (26.9%). Heart rate (HR), white blood cell count, the percentage of blood neutrophils, serum glucose and triglycerides were correlated with the severity of APIP. The ability of HR to predict severe acute pancreatitis (SAP) was highest. There were no maternal deaths reported. The overall fetal mortality rate was 7.7% and 62.5% experienced neonatal asphyxia in SAP. Apgar scores among newborns of mild acute pancreatitis (MAP) were not different. Conclusions: The most frequent cause of APIP has changed and hypertriglyceridemia was the most common cause of APIP. The initial HR recorded after admission might be the new predictor of SAP. The severity of APIP was associated with higher risk of neonatal asphyxia. For MAP patients, conservative treatment was also desirable.

In navigating the complexities of social life, humans have evolved to interpret invisible odorous chemical cues, with profound behavioural impacts often unbeknown to the conscious mind. The manifestation of this in humans is evident in the scent of androstadienone (androsta-4,16-dien-3-one), an odorous compound which is considered a putative human pheromone. The current study investigated the effect of androstadienone on social distance-dependent prosocial behaviour measured by a social discounting task, in which participants chose between selfish and generous options. Based on our pre-registration, we predicted a sex-specific effect, with males exposed to androstadienone exhibiting increased generosity, while females would choose more selfishly. Employing a double-blind, placebo-controlled, between-subject design, we recruited 170 participants who were randomly assigned to either the androstadienone or control condition. Olfactory stimuli were administered while participants completed the social discounting task. Inconsistent with our hypothesis, inhaling androstadienone did not impact social distance-dependent prosocial behaviour. This finding was supported by multiple estimates of prosociality, including model-free, model-based and maximum likelihood estimation. Further analyses indicated that androstadienone administration did not influence perceived social distance or bias participants towards being generous or selfish. Thus, our empirical findings provide no support for the hypothesis that androstadienone modulates generosity.

Abstract Acquired drug resistance is one of the most common limitations for the clinical response of colon cancer to 5-Fluorouracil (5-FU)-based chemotherapy. The relevant molecular mechanisms might be diversity, but still not be elucidated clearly. In this study, we aimed to investigate the potential mechanisms of c-Fos, a subfamily of activator protein-1, in 5-FU chemoresistance. We determined that phosphorylated c-Fos promoted colon cancer cells resistance to 5-FU by facilitating the cancer stemness. Mechanically, 5-FU treatment induced autolysosome-dependent degradation of TMPO, which subsequently triggered ERK-mediated phosphorylation of c-Fos. Additionally, c-Fos was found to bind to the promoter of NANOG and phosphorylation of c-Fos at Ser 374 was required for its regulation of NANOG expression. NANOG ablation impaired c-Fos/p-c-Fos induced 5-FU resistance and stemness. Taken together, these findings revealed that TMPO-mediated phosphorylation of c-Fos conferred 5-FU resistance by regulating NANOG expression and promoting cell stemness in colon cancer cells. c-Fos could be as a therapeutic target for colon cancer.

Abstract Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits.

The development of ice-melting probes is driven by the scientific need to explore the subglacial aquatic environments, such as the subglacial lakes in Antarctica and subglacial water on some extraterrestrial planets. However, during the downward melting, a deviation of the melting trajectory might occur. If left unaddressed, the accumulated deviation will eventually lead to missing the probe's target. Therefore, it is necessary to build a theoretical model to describe the deviation for predicting the future melting trajectory and building the deviation correction system. The deviation comes from any asymmetric heating condition on the melting head. Generally, the Close-Contact Melting (CCM) theory is used to model the probe's melting process without any deviation, and there is only one attempt so far that applies the CCM theory to asymmetric heating conditions. Based on this initial attempt, we successfully expanded the CCM theory with asymmetric temperature profiles to conical thermal heads. Additionally, we simplified the model solving which leads to fewer influence factors compared to existing studies. The model indicates that the melting trajectory of a conical head is linear under asymmetric heating conditions, and the inclination angle of the trajectory is related to the ratio between the head's temperatures on each side and the head's cone angle. To validate the theoretical results, laboratory experiments have also been conducted with an innovative optical positioning method.

Currently, the multi-machine collaboration of agricultural machinery is one of the international frontiers and a topic of research interest in the field of agricultural equipment. However, the multi-machine cooperative operation of agricultural machinery is mostly limited to the research on task goal planning and cooperative path optimization of a single operation. To address the mentioned shortcomings, this study addresses the problem of multi-machine cooperative operation of fertilizer applicators in fields with different fertility and fertilizer cooperative distribution of fertilizer trucks. The research uses the task allocation method of a multi-machine cooperative operation of applying fertilizer-transporting fertilizer. First, the problems of fertilizer applicator operation and fertilizer truck fertilizer distribution are defined, and the operating time and the distribution distance are used as optimization objectives to construct functions to establish task allocation mathematical models. Second, a Chaos–Cauchy Fireworks Algorithm (CCFWA), which includes a discretized decoding method, a population initialization with a chaotic map, and a Cauchy mutation operation, is developed. Finally, the proposed algorithm is verified by tests in an actual scenario of fertilizer being applied in the test area of Jimo District, Qingdao City, Shandong Province. The results show that compared to the Fireworks Algorithm, Genetic Algorithm, and Particle Swarm Optimization, the proposed CCFWA can address the problem of falling into a local optimum while guaranteeing the convergence speed. Also, the variance of the CCFWA is reduced by more than 48% compared with the other three algorithms. The proposed method can realize multi-machine cooperative operation and precise distribution of seeds and fertilizers for multiple seeding-fertilizer applicators and fertilizer trucks.

Abstract Free-spectral-range (FSR)-free optical filters have always been a critical challenge for photonic integrated circuits. A high-performance FSR-free filter is highly desired for communication, spectroscopy, and sensing applications. Despite significant progress in integrated optical filters, the FSR-free filter with a tunable narrow-band, high out-of-band rejection, and large fabrication tolerance has rarely been demonstrated. In this paper, we propose an exact and robust design method for add-drop filters (ADFs) with an FSR-free operation capability, a sub-nanometer optical bandwidth, and a high out-of-band rejection (OBR) ratio. The achieved filter has a 3-dB bandwidth of

Choices between immediate smaller reward and long-term larger reward are referred to as intertemporal choice. Numerous functional magnetic resonance imaging (fMRI) studies have investigated the neural substrates of intertemporal choice via conventional univariate analytical approaches, revealing dissociable activations of decisions involving immediately available rewards and decisions involving delayed rewards in value network. With the help of multivariate analyses, which is more sensitive for evaluating information encoded in spatially distributed patterns, we showed that fMRI activity patterns represent viable signatures of intertemporal choice, as well as individual differences while controlling for age. Notably, in addition to value network, regions from cognitive control network play prominent roles in differentiating between different intertemporal choices as well as individuals with distinct discount rates. These findings provide clear evidence that substantiates the important role of value and cognitive control networks in the neural representation of one’s intertemporal decisions.

The melting water produced from ice during hot-point drilling can easily freeze and cause the hot-point drill to stick. Two different thermal anti-freezing methods exist to prevent water-filled boreholes from refreezing: the heating cable method and lateral heating method. However, the required power density and ice temperature distribution when using these two methods have not been fully discussed. In this study, heat transfer models of the two thermal anti-freezing methods were first developed based on a simplified heat conduction equation by considering the downward movement of the hot-point drill. Subsequently, case studies were conducted to determine the characteristics of the heat transfer during hot-point drilling. Finally, the variations in the power density, power consumption, borehole closure time, borehole closure length, and thermal layer thickness for both thermal anti-freezing methods were evaluated. We recommend that the heating cable method should be used to drill boreholes with shallow depths or small diameters in temperate ice, whereas the lateral heating method can be applied to a wide range of ice temperatures, borehole diameters, and borehole depths. Generally, the paper presents useful guidance for designing the heating cable and lateral heater and reducing the risk of borehole freezing.

Nε-lysine acetylation is a reversible posttranslational modification (PTM) involved in multiple physiological functions. Genetic and animal studies have documented the critical roles of protein acetylation in brain development, functions, and various neurological disorders. However, the underlying cellular and molecular mechanism are still partially understood. Here, we profiled and characterized the mouse brain acetylome and investigated the cellular distribution of acetylated brain proteins. We identified 1,818 acetylated proteins, including 5,196 acetylation modification sites, using a modified workflow comprising filter-aided sample preparation (FSAP), acetylated peptides enrichment, and MS analysis without pre- or post-fraction. Bioinformatics analysis indicated these acetylated mouse brain proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and synapse, as well as their involvement in multiple neurological disorders. Manual annotation revealed that a set of brain-specific proteins were acetylation-modified. The acetylation of three brain-specific proteins was verified, including neurofilament light polypeptide (NEFL), 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNP), and neuromodulin (GAP43). Further immunofluorescence staining illustrated that acetylated proteins were mainly distributed in the nuclei of cortex neurons and axons of hippocampal neurons, sparsely distributed in the nuclei of microglia and astrocytes, and the lack of distribution in both cytoplasm and nuclei of cerebrovascular endothelial cells. Together, this study provided a comprehensive mouse brain acetylome and illustrated the cellular-specific distribution of acetylated proteins in the mouse brain. These data will contribute to understanding and deciphering the molecular and cellular mechanisms of protein acetylation in brain development and neurological disorders. Besides, we proposed some problems that need to be solved in future brain acetylome research.

Nitric oxide (NO), a bioactive molecule, is often involved in the regulation of physiological and biochemical processes in stressed plants. However, the effects of NO donors on dioecious plants remain unclear. Using a pot experiment, female and male Torreya grandis were used to study the role of sex and NO in salt stress tolerance. In the present study, female and male T. grandis seedlings pretreated with an NO donor (sodium nitroprusside, SNP) were exposed to salt stress, and then leaf relative water content (RWC), photosynthetic pigments, chlorophyll fluorescence parameters, NO and glutathione levels, oxidative damage, and antioxidant enzyme activities were investigated. Female T. grandis plants had better tolerance to salinity, as they were characterized by significantly higher RWC, pigment content, and photochemical activities of photosystem II (PSII) and fewer negative effects associated with higher nitrate reductase (NR) activity and NO content. Pretreatment with an NO donor further increased the endogenous NO content and NR activity of both female and male T. grandis plants compared with salt treatment. Moreover, pretreatment with an NO donor alleviated salt-induced oxidative damage of T. grandis, especially in male plants, as indicated by reduced lipid peroxidation, through an enhanced antioxidant system, including proline and glutathione accumulation, and increased antioxidant enzyme activities. However, the ameliorating effect of the NO donor was not effective in the presence of the NO scavenger (Nω-nitro-L-arginine methyl ester, L-name). In conclusion, enhanced salt tolerance in T. grandis plants is related to nitric oxide levels and the supply of NO donors is an interesting strategy for alleviating the negative effect of salt on T. grandis. Our data provide new evidence to contribute to the current understanding of NO-induced salt stress tolerance.

Summary: Compared with the noble-metal surface-enhanced Raman scattering (SERS) substrates activated by the surface plasmon resonance (SPR)-induced electromagnetic mechanism (EM), the relative low sensitivity and stability of the chemical mechanism (CM)-based substrates are the biggest obstacles to their applications. Herein, we report that quasi-metallic VO2 nanosheet arrays can be used as a sensitive and stable SERS substrate. The lowest detectable limit of analyte adsorbed on the VO2 nanosheets achieves 10−10 M and the maximum Raman enhancement factor (EF) reaches 6.7 × 107, which is comparable with that of the noble metals. The experimental and theoretical results demonstrate that the SERS performance of the VO2 nanosheets comes from the strong interfacial interactions based on charge transfer and the vigorous SPR effects. Our research results demonstrate that quasi-metals are very promising SERS detection platforms and reveal that CM, like EM, contributes significantly to the SERS activity of quasi-metals. : Physical Chemistry; Electromagnetics; Materials Property; Nanomaterials Subject Areas: Physical Chemistry, Electromagnetics, Materials Property, Nanomaterials

MicroRNAs are a group of endogenous small non-coding RNAs commonly dysregulated in tumorigenesis, including glioblastoma (GBM), the most malignant brain tumor with rapid proliferation, diffuse invasion, and therapeutic resistance. Accumulating evidence has manifested that miR-1258 exerts an inhibitory role in many human cancers. However, the expression pattern of miR-1258 and its potential function in GBM tumorigenesis remain unclear. In this study, we reported that miR-1258 expression decreased with the ascending pathological grade of glioma, which indicated an unfavorable prognosis of patients. Functional assays revealed an inhibitory effect of miR-1258 on malignant proliferation, therapeutic resistance, migration, and invasion of GBM in vitro. Moreover, xenograft models also suggested a repression effect of miR-1258 on gliomagenesis. Mechanistically, miR-1258 directly targeted E2F1 in 3’-untranslated regions and attenuated E2F1-mediated downstream gene PCNA and MMP2 transcriptions. Furthermore, restoration of E2F1 expression in GBM cells effectively rescued the tumor-suppressive effect of miR-1258. Our studies illustrated that miR-1258 functioned as a tumor suppressor in GBM by directly targeting E2F1, subsequently inhibiting PCNA and MMP2 transcriptions, which contributed to new potential targets for GBM therapy and other E2F1-driven cancers.

There has been accumulating evidence of human social chemo-signaling, but the underlying mechanisms remain poorly understood. Considering the evolutionarily conserved roles of oxytocin and vasopressin in reproductive and social behaviors, we examined whether the two neuropeptides are involved in the subconscious processing of androsta-4,16,-dien-3-one and estra-1,3,5 (10),16-tetraen-3-ol, two human chemosignals that convey masculinity and femininity to the targeted recipients, respectively. Psychophysical data collected from 216 heterosexual and homosexual men across five experiments totaling 1056 testing sessions consistently showed that such chemosensory communications of masculinity and femininity were blocked by a competitive antagonist of both oxytocin and vasopressin receptors called atosiban, administered nasally. On the other hand, intranasal oxytocin, but not vasopressin, modulated the decoding of androstadienone and estratetraenol in manners that were dose-dependent, nonmonotonic, and contingent upon the recipients’ social proficiency. Taken together, these findings establish a causal link between neuroendocrine factors and subconscious chemosensory communications of sex-specific information in humans.

Summary: As a non-destructive and label-free detection technology, surface-enhanced Raman scattering (SERS) has been widely used in environmental-pollutant detection, biological-tissue sensing, molecular fingerprint analysis, and so on. Herein, we report an active SERS material, namely quasi-metallic WO2 nanodendrites. Due to the dual boosts of electromagnetic mechanism (EM) enhancement and chemical mechanism (CM) enhancement, the WO2 nanodendrites achieve an 8.5 × 107 level enhanced factor and a 10−10 level detection limit for probe molecules. The experimental and theoretical results demonstrate that the performance comes from the dual enhancement of the highly efficient interface charge transfer and the vigorous surface plasma resonance (SPR) of the quasi-metals. Furthermore, these WO2 nanodendrites show high chemical stability, are resistant to long-term air oxidation, and even can endure strong acid and alkali corrosion without reducing their SERS activity. The separation and detection of multicomponent samples are achieved simultaneously when these nanodendrites are fabricated into patterned SERS chips.

The mid-infrared (MIR, 2–20 μm) waveband is of great interest for integrated photonics in many applications such as on-chip spectroscopic chemical sensing, and optical communication. Thermo-optic switches are essential to large-scale integrated photonic circuits at MIR wavebands. However, current technologies require a thick cladding layer, high driving voltages or may introduce high losses in MIR wavelengths, limiting the performance. This paper has demonstrated thermo-optic (TO) switches operating at 2 μm by integrating graphene onto silicon-on-insulator (SOI) structures. The remarkable thermal and optical properties of graphene make it an excellent heater material platform. The lower loss of graphene at MIR wavelength can reduce the required cladding thickness for the thermo-optics phase shifter from micrometers to tens of nanometers, resulting in a lower driving voltage and power consumption. The modulation efficiency of the microring resonator (MRR) switch was 0.11 nm/mW. The power consumption for 8-dB extinction ratio was 5.18 mW (0.8 V modulation voltage), and the rise/fall time was 3.72/3.96 μs. Furthermore, we demonstrated a 2 × 2 Mach-Zehnder interferometer (MZI) TO switch with a high extinction ratio of more than 27 dB and a switching rise/fall time of 4.92/4.97 μs. A comprehensive analysis of the device performance affected by the device structure and the graphene Fermi level was also performed. The theoretical figure of merit (2.644 mW−1μs−1) of graphene heaters is three orders of magnitude higher than that of metal heaters. Such results indicate graphene is an exceptional nanomaterial for future MIR optical interconnects.

Over the past few years, Spiking Neural Networks (SNNs) have become popular as a possible pathway to enable low-power event-driven neuromorphic hardware. However, their application in machine learning have largely been limited to very shallow neural network architectures for simple problems. In this paper, we propose a novel algorithmic technique for generating an SNN with a deep architecture, and demonstrate its effectiveness on complex visual recognition problems such as CIFAR-10 and ImageNet. Our technique applies to both VGG and Residual network architectures, with significantly better accuracy than the state-of-the-art. Finally, we present analysis of the sparse event-driven computations to demonstrate reduced hardware overhead when operating in the spiking domain.

Current standard practices for treatment of cancers are less than satisfactory because of recurrence mediated by cancer stem cells (CSCs). Caffeic acid (CaA) is a novel anti‐tumor agent that inhibits proliferation, migration, and invasion in human cancer cells. However, little is known about the functions of CaA in regulating CSCs‐like properties and the potential molecular mechanisms. Here, we found that CaA attenuated the CSCs‐like properties by the microRNA‐148a (miR‐148a)‐mediated inhibition of transforming growth factor beta (TGFβ)‐SMAD2 signaling pathway bothin vitro andin vivo. CaA enhanced the expression of miR‐148a by inducing DNA methylation. MiR‐148a, which targeted theSMAD2‐3′UTR, decreased the expression of SMAD2. Knockdown of miR‐148a abolished the CaA‐induced inhibition of TGFβ‐SMAD2 signal pathway and the CSCs‐like properties. Our study found a novel mechanism that CaA inhibits the CSCs‐like properties via miR‐148a‐mediated inhibition of TGFβ‐SMAD2 signaling pathway, which may help to identify a new approach for the treatment of human cancers.

Mitochondria in eukaryotic cells are derived from bacteria in evolution. Like bacteria, mitochondria contain DNA with unmethylated CpG motifs and formyl peptides, both of which have recently been shown to be damage associated molecular patterns (DAMPs) and induce immune response and cell injury. Based on the facts that circulating mitochondrial DAMPs (mtDAMPs) are increased in the patients of trauma or burn injury who also have proteinuria, that mtDAMPs can activate immune cells which in turn secrete glomerular permeability factors, that renal intrinsic cells express a variety of DAMP receptors, and that mtDAMPs can directly increase endothelial cell permeability in vitro, we hypothesized that mtDAMPs may be novel circulating factors inducing proteinuria and kidney injury. We tested this hypothesis by directly injecting mtDAMPs into rodents and examining urinary protein and kidney histology. We prepared mtDAMP samples, including mitochondrial DNA (mtDNA) and mitochondrial debris (MTD), from rodent liver. In mice, injection of mtDNA for 20 μg/ml initial concentration in circulation (much higher than the clinical range), did not cause any renal manifestations. However, an increased dose leading to 45 μg/ml initial concentration in circulation resulted in a transient, slight increase in urinary albumin. In rats, MTD injection resulting in 450 μg/ml initial concentration of MTD protein in circulation, which was much higher than the clinical range, caused mild, transient proteinuria and lung lesions. Multiple injections of such large amount of either mtDNA or MTD into rodents on 3 consecutive days also failed in inducing proteinuria and kidney injury. In summary, clinical levels of circulating mtDAMPs do not induce proteinuria and clinically irrelevant high levels of mtDAMPs cause only a transient and slight increase in urinary protein in rodents, suggesting that circulating mtDAMPs may not be responsible for the proteinuria and kidney injury in patients with trauma, burn injury, and other diseases.

Deltamethrin (DM) insecticides are currently being promoted worldwide for mosquito control, because of the high efficacy, low mammalian toxicity and less environmental impact. Widespread and improper use of insecticides induced resistance, which has become a major obstacle for the insect-borne disease management. Resistance development is a complex and dynamic process involving many genes. To better understand the possible molecular mechanisms involved in DM resistance, a proteomic approach was employed for screening of differentially expressed proteins in DM-susceptible and -resistant mosquito cells. Twenty-seven differentially expressed proteins were identified by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). Four members of the ubiquitin-proteasome system were significantly elevated in DM-resistant cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM resistance. Proteasome subunit beta type 6 (PSMB6) is a member of 20S proteasomal subunit family, which forms the proteolytic core of 26S proteasome. We used pharmaceutical inhibitor and molecular approaches to study the contributions of PSMB6 in DM resistance: the proteasome inhibitor MG-132 and bortezomib were used to suppress the proteasomal activity and siRNA was designed to block the function of PSMB6. The results revealed that both MG-132 and bortezomib increased the susceptibility in DM-resistant cells and resistance larvae. Moreover, PSMB6 knockdown decreased cellular viability under DM treatment. Taken together, our study indicated that PSMB6 is associated with DM resistance in mosquitoes and that proteasome inhibitors such as MG-132 or bortezomib are suitable for use as a DM synergist for vector control.