AANAT1 regulates insect midgut detoxification through the ROS/CncC pathway.

Insecticide resistance has been a problem in both the agricultural pests and vectors. Revealing the detoxification mechanisms may help to better manage insect pests. Here, we showed that arylalkylamine N-acetyltransferase 1 (AANAT1) regulates intestinal detoxification process through modulation of reactive oxygen species (ROS)-activated transcription factors cap"n"collar isoform-C (CncC): muscle aponeurosis fibromatosis (Maf) pathway in both the oriental fruit fly, Bactrocera dorsalis, and the arbovirus vector, Aedes aegypti. Knockout/knockdown of AANAT1 led to accumulation of biogenic amines, which induced a decreased in the gut ROS level. The reduced midgut ROS levels resulted in decreased expression of CncC and Maf, leading to lower expression level of detoxification genes. AANAT1 knockout/knockdown insects were more susceptible to insecticide treatments. Our study reveals that normal functionality of AANAT1 is important for the regulation of gut detoxification pathways, providing insights into the mechanism underlying the gut defense against xenobiotics in metazoans.

SEEG-RFTC in patients with refractory focal epilepsy: real-world outcomes from 121 cases.

OBJECTIVE: Radiofrequency thermocoagulation (RFTC) has emerged as an effective and safe treatment method for patients with refractory focal epilepsy, when stereo-electroencephalography (SEEG) is implanted. Although real-world research results are still limited, a considerable number of patients have shown favorable outcomes with this less invasive method. This study aims to describe the outcomes and predictive factors of SEEG-RFTC in real-world research. METHODS: A retrospective observational study was conducted on patients in the authors' epilepsy center. In total, 121 patients who underwent RFTC were included in the study. Post-RFTC outcomes were evaluated using the seizure-free rate and response rate (seizure frequency reduction more than 50%). Predictive factors influencing post-RFTC outcome were considered by comparing different variables. RESULTS: The mean follow-up period was 18.3 months. Eighty-two patients (67.8%) were responders and 54 (44.6%) were seizure free. In 36 patients with malformation of cortical development, the seizure-free rate and the response rate were 69.44% and 83.33%, respectively. In 20 patients with hippocampal sclerosis, 19 patients were responders and 14 (70%) patients were seizure free at the last follow-up. The MRI feature and etiology of epilepsy are correlated with the outcome. MR-positive is a predictive factor for seizure freedom (p < 0.01) and responders (p < 0.01). Other factors have no predictive value for post-RFTC outcome. INTERPRETATION: SEEG-RFTC is a safe procedure and yields favorable outcomes in numerous cases of focal DRE. The MRI feature and etiology of epilepsy are correlated with the seizure-free rate and response rate. And MRI positivity is the predictor for good RFTC outcome.

A cross-scenario and cross-subject domain adaptation method for driving fatigue detection.

Objective.The scarcity of electroencephalogram (EEG) data, coupled with individual and scenario variations, leads to considerable challenges in real-world EEG-based driver fatigue detection. We propose a domain adaptation method that utilizes EEG data collected from a laboratory to supplement real-world EEG data and constructs a cross-scenario and cross-subject driver fatigue detection model for real-world scenarios.Approach.First, we collect EEG data from subjects participating in a driving experiment conducted in both laboratory and real-world scenarios. To address the issue of data scarcity, we build a real-world fatigued driving detection model by integrating the real-world data with the laboratory data. Then, we propose a method named cross-scenario and cross-subject domain adaptation (CS2DA), which aims to eliminate the domain shift problem caused by individual variances and scenario differences. Adversarial learning is adopted to extract the common features observed across different subjects within the same scenario. The multikernel maximum mean discrepancy (MK-MMD) method is applied to further minimize scenario differences. Additionally, we propose a conditional MK-MMD constraint to better utilize label information. Finally, we use seven rules to fuse the predicted labels.Main results.We evaluate the CS2DA method through extensive experiments conducted on the two EEG datasets created in this work: the SEED-VLA and the SEED-VRW datasets. Different domain adaptation methods are used to construct a real-world fatigued driving detection model using data from laboratory and real-world scenarios, as well as a combination of both. Our findings show that the proposed CS2DA method outperforms the existing traditional and adversarial learning-based domain adaptation approaches. We also find that combining data from both laboratory and real-world scenarios improves the performance of the model.Significance.This study contributes two EEG-based fatigue driving datasets and demonstrates that the proposed CS2DA method can effectively enhance the performance of a real-world fatigued driving detection model.

Essentials of CAR-T Therapy and Associated Microbial Challenges in Long Run Immunotherapy.

Chimeric antigen receptor (CAR)-T cell therapy has shown potential in improving outcomes for individuals with hematological malignancies. However, achieving long-term full remission for blood cancer remains challenging due to severe life-threatening toxicities such as limited anti-tumor efficacy, antigen escape, trafficking restrictions, and limited tumor invasion. Furthermore, the interactions between CAR-T cells and their host tumor microenvironments have a significant impact on CAR-T function. To overcome these considerable hurdles, fresh methodologies and approaches are needed to produce more powerful CAR-T cells with greater anti-tumor activity and less toxicity. Despite advances in CAR-T research, microbial resistance remains a significant obstacle. In this review, we discuss and describe the basics of CAR-T structures, generations, challenges, and potential risks of infections in CAR-T cell therapy.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation.

BACKGROUND: Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM: To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS: Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS: Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION: AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

Diffuse hyperpigmentation with guttate hypopigmentation: a new pigmentary disorder.

Diffuse hyperpigmentation with guttate hypopigmentation (DHGH) is a new acquired pigmentary disorder. Only a few cases have previously been reported in the Chinese population, in Chinese. To summarise the clinical, dermoscopic, and histopathological findings of DHGH in the English literature, to improve the recognition and management of this condition. This was a retrospective study to summarise the clinical, dermoscopic, and pathological findings of nine cases of DHGH. All nine patients with DHGH were female. The age at onset varied from 6 to 24 years (median 17 years). Patients were generally in good health without systemic disease. The lesions were often generalised to the trunk and extremities without any discomfort. Typical lesions were characterised by multiple uniform hypopigmented spots, 2-5 mm in diameter, irregularly distributed over diffuse hyperpigmentation. Dermoscopy revealed multiple blurred patchy areas of brownish pigmentation, sparse linear and dotted vessels, and perifollicular pigmentation on a white to bright white background, surrounded by brown hyperpigmentation. Histopathological findings included mild abnormal pigment of the epidermis, focal vacuolar degeneration of the basal cells, mild pigment incontinence and perivascular lymphocytic infiltration in the dermis. DHGH is a new entity with distinctive clinical manifestations that differ from those of other known pigmentary disorders. So far, DHGH has only been reported in the Chinese population. It may not be uncommon and has not received much attention due to the few reports. The aetiology and pathogenesis of DHGH are still unknown and require further investigation.

Three new species of Neohelicomyces (Tubeufiales, Tubeufiaceae) from freshwater and terrestrial habitats in China.

Neohelicomyces species are a group of helicosporous hyphomycetes with the potential to produce secondary metabolites. During our investigation of helicosporous fungi, six collections were isolated from both terrestrial and freshwater habitats in Guizhou Province, China. Based on multigene phylogenetic analysis (ITS, LSU, tef1α and rpb2), coupled with morphological data, three new Neohelicomyces species, viz. N.guizhouensis, N.helicosporus and N.hydei were established. A list of accepted Neohelicomyces species with molecular data was provided. The strain of Neohelicomycespallidus (UAMH 10535) was synonymised under N.denticulatus based on molecular data.

Distinct patterns of electrophysiologic-neuroimaging correlations between Parkinson's disease and multiple system atrophy.

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.

Characterization of an agmatine N-acetyltransferase from Bactrocera dorsalis that modulates ovary development.

Agmatine N-acetyltransferase (AgmNAT), which catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine, is a member of the GCN5-related N-acetyltransferase family. So far, knowledge of the physiological roles of AgmNAT in insects is limited. Here, we identified one gene encoding protein homologous to that of Drosophila AgmNAT using sequence information from an activity-verified Drosophila AgmNAT in a BLAST search of the Bactrocera dorsalis genome. We expressed and purified B. dorsalis AgmNAT in Escherichia coli and used the purified enzyme to define the substrate specificity for acyl-CoA and amine substrates. Our application of the screening strategy to BdorAgmNAT led to the identification of agmatine as the best amine substrate for this enzyme, with the highest kcat/Km value. We successfully obtained a BdorAgmNAT knockout strain based on a wild-type strain (WT) using the CRISPR/Cas9 technique. The ovary development of the BdorAgmNAT knockout mutants was delayed for 10 days compared with the WT specimens. Moreover, mutants had a much smaller mature ovary size and laid far fewer eggs than WT. Loss of function of BdorAgmNAT caused by RNAi with mature WT females did not affect their fecundity. These findings indicate that BdorAgmNAT is critical for oogenesis. Our data provide the first evidence for AgmNAT in regulating ovary development.

Deciphering CD4+ T cell-mediated responses against cancer.

It's been long thought that CD8+ cytotoxic T cells play a major role in T cell-mediated antitumor responses, whereas CD4+ T cells merely provide some assistance to CD8+ T cells as the "helpers." In recent years, numerous studies support the notion that CD4+ T cells play an indispensable role in antitumor responses. Here, we summarize and discuss the current knowledge regarding the roles of CD4+ T cells in antitumor responses and immunotherapy, with a focus on the molecular and cellular mechanisms behind these observations. These new insights on CD4+ T cells may pave the way to further optimize cancer immunotherapy.

Toxicity of Beauveria bassiana to Bactrocera dorsalis and effects on its natural predators.

Entomopathogenic fungi (EPF) are economical and environmentally friendly, forming an essential part of integrated pest management strategies. We screened six strains of Beauveria bassiana (B1-B6) (Hypocreales: Cordycipitaceae), of which B4 was the most virulent to Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). We further assessed the biological characteristics of strain B4 and the environmental factors influencing its ability to infect B. dorsalis. We also evaluated the effects of B4 on two of the natural predators of B. dorsalis. We found that strain B4 was the most virulent to 3rd instar larvae, pupae, and adult B. dorsalis, causing mortality rates of 52.67, 61.33, and 90.67%, respectively. B4 was not toxic to B. dorsalis eggs. The optimum B4 effects on B. dorsalis were achieved at a relative humidity of 91-100% and a temperature of 25°C. Among the six insecticides commonly used for B. dorsalis control, 1.8% abamectin emulsifiable concentrate had the strongest inhibitory effect on B4 strain germination. B4 spraying affected both natural enemies (Amblyseius cucumeris and Anastatus japonicus), reducing the number of A. cucumeris and killing A. japonicus adults. We found a valuable strain of EPF (B4) that is virulent against many life stages of B. dorsalis and has great potential for the biological control of B. dorsalis. We also provide an important theoretical and practical base for developing a potential fungicide to control B. dorsalis.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres.

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

High-capacity dilithium hydroquinone cathode material for lithium-ion batteries.

Lithiated organic cathode materials show great promise for practical applications in lithium-ion batteries owing to their Li-reservoir characteristics. However, the reported lithiated organic cathode materials still suffer from strict synthesis conditions and low capacity. Here we report a thermal intermolecular rearrangement method without organic solvents to prepare dilithium hydroquinone (Li2Q), which delivers a high capacity of 323 mAh g-1 with an average discharge voltage of 2.8 V. The reversible conversion between orthorhombic Li2Q and monoclinic benzoquinone during charge/discharge processes is revealed by in situ X-ray diffraction. Theoretical calculations show that the unique Li-O channels in Li2Q are beneficial for Li+ ion diffusion. In situ ultraviolet-visible spectra demonstrate that the dissolution issue of Li2Q electrodes during charge/discharge processes can be handled by separator modification, resulting in enhanced cycling stability. This work sheds light on the synthesis and battery application of high-capacity lithiated organic cathode materials.

High-Performance W-Doped Bi0.5Sb1.5Te3 Flexible Thermoelectric Films and Generators.

Bi-Sb-Te-based thermoelectric materials have the best room-temperature thermoelectric properties, but their inherent brittleness and rigidity limit their application in the wearable field. In this study, W-doped p-type Bi0.5Sb1.5Te3 (W-BST) thin films were prepared using magnetron sputtering on polyimide substrates to create thermoelectric generators (TEGs). Bending tests showed that the thin film has excellent flexibility and mechanical durability, meeting the flexible requirements of wearable devices. W doping can significantly increase the carrier concentration, Seebeck coefficient, and electrical conductivity of BST thin films. At 300 K, the power factor of the W-BST film is 2.25 times higher than that of the undoped film, reaching 13.75 µW cm-1 K-2. First-principles calculations showed that W doping introduces significant impurity peaks in the bandgap, in which W d electrons remarkably hybridize with the Sb and Te p electrons, leading to an improved electrical conductivity of BST films. Furthermore, W doping significantly reduces the work function of BST films, thereby improving the carrier mobility. A TEG module fabricated from four layers of W-BST thin films achieved a maximum output power density of 6.91 mW cm-2 at a temperature difference of 60 K. Application tests showed that the flexible TEG module could power a portable clock using the temperature difference between body temperature and room temperature. At a medium temperature of 439 K, the assembled TEG module can provide a stable output voltage of 1.51 V to power a LED. This study demonstrates the feasibility of combining inorganic thermoelectric materials with flexible substrates to create high-performance flexible TEGs.

Gallic acid-loaded HFZIF-8 for tumor-targeted delivery and thermal-catalytic therapy.

"Transition" metal-coordinated plant polyphenols are a type of promising antitumor nanodrugs owing to their high biosafety and catalytic therapy potency; however, the major obstacle restricting their clinical application is their poor tumor accumulation. Herein, Fe-doped ZIF-8 was tailored using tannic acid (TA) into a hollow mesoporous nanocarrier for gallic acid (GA) loading. After hyaluronic acid (HA) modification, the developed nanosystem of HFZIF-8/GA@HA was used for the targeted delivery of Fe ions and GA, thereby intratumorally achieving the synthesis of an Fe-GA coordinated complex. The TA-etching strategy facilitated the development of a cavitary structure and abundant coordination sites of ZIF-8, thus ensuring an ideal loading efficacy of GA (23.4 wt%). When HFZIF-8/GA@HA accumulates in the tumor microenvironment (TME), the framework is broken due to the competitive protonation ability of overexpressed protons in the TME. Interestingly, the intratumoral degradation of HFZIF-8/GA@HA provides the opportunity for the in situ "meeting" of GA and Fe ions, and through the coordination of polyhydroxyls assisted by conjugated electrons on the benzene ring, highly stable Fe-GA nanochelates are formed. Significantly, owing to the electron delocalization effect of GA, intratumorally coordinated Fe-GA could efficiently absorb second near-infrared (NIR-II, 1064 nm) laser irradiation and transfer it into thermal energy with a conversion efficiency of 36.7%. The photothermal performance could speed up the Fenton reaction rate of Fe-GA with endogenous H2O2 for generating more hydroxyl radicals, thus realizing thermally enhanced chemodynamic therapy. Overall, our research findings demonstrate that HFZIF-8/GA@HA has potential as a safe and efficient anticancer nanodrug.

Visible light-driven photocatalytic sulfonative oxidation of benzyl secondary amines.

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

Nonaggregated Anions Enable the Undercooled Aqueous Electrolyte for Low-Temperature Applications.

Aqueous batteries, with the advantages of high safety and low cost, are highly promising for large-scale energy storage. However, freezing of the aqueous electrolyte limits the low-temperature operation. Here, we propose and achieve a highly dispersed solvation structure in the electrolyte by coupling nonaggregated Cl- anions, which reduces the water cluster size and prevents the solidification of the aqueous electrolyte until -136.3 °C. The low-temperature LiCl electrolyte exhibits a high ionic conductivity (1.0 mS cm-1) at -80 °C and enables a stable low-temperature Ag/AgCl reference electrode at -50 °C. Moreover, the polyaniline-based battery can work at an extremely low temperature of -100 °C and shows superior cycling performance of 4000 cycles at -40 °C with 95.7% capacity retention. This work elucidates the correlation between the anion effect and the thermodynamic transition of the electrolyte, offering a novel approach for designing low-temperature electrolytes.

The complete chloroplast genome of Hemiboea pterocaulis (Gesneriaceae) exclusively distributed in Guilin, Guangxi, China.

Hemiboea pterocaulis is a unique species only found in Guilin, Guangxi, China. In this study, we sequenced and assembled the complete chloroplast genome of H. pterocaulis and revealed its phylogenetic relationship with other Hemiboea species. The chloroplast genome sequence of H. pterocaulis is 153,159 bp in length and comprises a large single-copy (LSC) region of 84,178 bp, a small single-copy (SSC) region of 18,087 bp, and a pair of inverted repeat (IR) regions, each with a length of 25,447 bp. It has a total GC content of 37.6% and encodes 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic relationships based on the complete chloroplast genome sequences of Hemiboea taxa indicate that H. pterocaulis is most closely related to H. suiyangensis, indicating that H. pterocaulis is an independent species and is separated from the H. subcapitata complex. These results provide valuable insights into the phylogeny, species divergence, and delimitation of the Hemiboea genus.

Comparative genomics of macaques and integrated insights into genetic variation and population history.

The crab-eating macaques ( Macaca fascicularis ) and rhesus macaques ( M. mulatta ) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is ∼42% lower, while centromeres are ∼3.7 times longer than those in humans. The characterization of ∼2 Mbp fixed genetic variants and ∼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1 ). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO ). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2 ). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1 , SEMA3F , and HOXD13 ). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.