Stabilization of dimeric PYR/PYL/RCAR family members relieves abscisic acid-induced inhibition of seed germination.

Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Deciphering the roles of bacterial and fungal communities in the formation and quality of agarwood.

Aquilaria sinensis is a significant resin-producing plant worldwide that is crucial for agarwood production. Agarwood has different qualities depending on the method with which it is formed, and the microbial community structures that are present during these methods are also diverse. Furthermore, the microbial communities of plants play crucial roles in determining their health and productivity. While previous studies have investigated the impact of microorganisms on agarwood formation, they lack comprehensiveness, particularly regarding the properties of the microbial community throughout the entire process from seedling to adult to incense formation. We collected roots, stems, leaves, flowers, fruits and other tissues from seedlings, healthy plants and agarwood-producing plants to address this gap and assess the dominant bacterial species in the microbial community structures of A. sinensis at different growth stages and their impacts on growth and agarwood formation. The bacteria and fungi in these tissues were classified and counted from different perspectives. The samples were sequenced using the Illumina sequencing platform, and sequence analyses and species annotations were performed using a range of bioinformatics tools to assess the plant community compositions. An additional comparison of the samples was conducted using diversity analyses to assess their differences. This research revealed that Listeria, Kurtzmanomyces, Ascotaiwania, Acinetobacter, Sphingobium, Fonsecaea, Acrocalymma, Allorhizobium, Bacillus, Pseudomonas, Peethambara, and Debaryomyces are potentially associated with the formation of agarwood. Overall, the data provided in this article help us understand the important roles played by bacteria and fungi in the growth and agarwood formation process of A. sinensis, will support the theoretical basis for the large-scale cultivation of A. sinensis, and provide a basis for further research on microbial community applications in agarwood production and beyond.

Advancing Ovarian Cancer Therapeutics: The Role of Targeted Drug Delivery Systems.

Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.

Deep brain stimulation and lag synchronization in a memristive two-neuron network.

In the pursuit of potential treatments for neurological disorders and the alleviation of patient suffering, deep brain stimulation (DBS) has been utilized to intervene or investigate pathological neural activities. To explore the exact mechanism of how DBS works, a memristive two-neuron network considering DBS is newly proposed in this work. This network is implemented by coupling two-dimensional Morris-Lecar neuron models and using a memristor synaptic synapse to mimic synaptic plasticity. The complex bursting activities and dynamical effects are revealed numerically through dynamical analysis. By examining the synchronous behavior, the desynchronization mechanism of the memristor synapse is uncovered. The study demonstrates that synaptic connections lead to the appearance of time-lagged or asynchrony in completely synchronized firing activities. Additionally, the memristive two-neuron network is implemented in hardware based on FPGA, and experimental results confirm the abundant neuronal electrical activities and chaotic dynamical behaviors. This work offers insights into the potential mechanisms of DBS intervention in neural networks.

Unraveling the secrets: Evolution of resistance mediated by membrane proteins.

Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development.

Enhanced water stability of MOFs via multiple hydrogen bonds and their application in water harvesting.

A mechanism based on multiple hydrogen bonds was proposed to describe the great water stability of some hydrated Cu paddle-wheel-based MOFs, which was demonstrated through density functional theory (DFT) calculations and single-crystal X-ray diffraction (SCXRD) of water-loaded MOFs. This mechanism endowed Cu-TDPAT with exceptional water stability and outstanding atmospheric water harvesting capability.

TpBD/UiO-66-NH2 micro-mesoporous hybrid material as a stationary phase for open tubular capillary electrochromatography.

The excellent stability of covalent organic frameworks (COFs) and the diversity of metal organic frameworks (MOFs) make MOF/COF hybrid materials promising candidates for chromatographic stationary phases. In this paper, a TpBD/UiO-66-NH2 hybrid material was synthesized through a Schiff-base reaction between TpBD COFs and UiO-66-NH2 MOFs; characterized using Fourier-transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy; and bonded to a capillary to prepare a TpBD/UiO-66-NH2-bonded open tubular capillary electrochromatography (OT-CEC) column. Results suggested that the hybrid material had the crystal morphology of a single COF and MOF, a micro-mesoporous structure, and good thermal stability. The inner surface of the OT-CEC column was tightly and uniformly distributed with the stationary phase (∼1.5 µm). The baseline separation of 13 amino acids and three families (4 acidic antibiotics, 4 preservatives and 6 sulfonamides) of emerging pollutant mixtures was achieved due to the synergistic effect of TpBD and UiO-66-NH2 in the stationary phase. The OT-CEC column showed good reproducibility and stability with relative standard deviations of migration time and resolutions in the range of 1.17-3.93% and 1.79-4.31%, respectively.

Phonon engineering of atomic-scale defects in superconducting quantum circuits.

Noise within solid-state systems at low temperatures can typically be traced back to material defects. In amorphous materials, these defects are broadly described by the tunneling two-level systems (TLSs) model. TLS have recently taken on further relevance in quantum computing because they dominate the coherence limit of superconducting quantum circuits. Efforts to mitigate TLS impacts have thus far focused on circuit design, material selection, and surface treatments. Our work takes an approach that directly modifies TLS properties. This is achieved by creating an acoustic bandgap that suppresses all microwave-frequency phonons around the operating frequency of a transmon qubit. For embedded TLS strongly coupled to the transmon qubit, we measure a pronounced increase in relaxation time by two orders of magnitude, with the longest T1 time exceeding 5 milliseconds. Our work opens avenues for studying the physics of highly coherent TLS and methods for mitigating noise within solid-state quantum devices.

A chondroitin sulphate hydrogel with sustained release of SDF-1α for extensive cartilage defect repair through induction of cell homing and promotion of chondrogenesis.

Articular cartilage damage represents a prevalent clinical disease in orthopedics, with its regeneration and repair constituting a central focus in ongoing research endeavors. While hydrogel technology has achieved notable progress in the field of cartilage regeneration, addressing the repair of larger cartilage defects remains a significant and formidable challenge. In pursuit of achieving the repair of extensive cartilage defects, this study designed a polydopamine-modified chondroitin sulfate hydrogel loaded with SDF-1α (P-SCMA). This hydrogel, capable of directly providing glycosaminoglycans (GAGs), served as a platform for carrying growth factors and attracting mesenchymal stem cells for the in situ reconstruction of extensive cartilage defects. The results indicate that the P-SCMA hydrogel is capable of not only directly providing GAGs but also sustainably releasing SDF-1α. In the early stages, it promotes cell adhesion and proliferation and induces cell homing, while in the later stages, it further induces chondrogenesis by inhibiting the Wnt/ß-catenin pathway. This bioactive hydrogel, which possesses the functions of providing GAGs, promoting cell proliferation, inducing cell homing and chondrogenesis, is capable of promoting cartilage repair in multiple ways, providing new perspectives for the repair of extensive cartilage defects.

A study on the effectiveness of narrative image types, message framing, and psychological distance in enhancing young people's self-efficacy in marine garbage recycling.

Intentional or unintentional littering, especially among young people, poses a threat to the marine environment. It is, therefore, necessary to enhance awareness of marine environmental protection among youth groups. This study explored the interaction between visual image types (photograph vs. cartoon), message framing (positive vs. negative), and psychological distance (human vs. turtle). A three-way analysis of variance (ANOVA) and regression analysis were used to verify the hypotheses. The key findings of the research were as follows: (1) Among the eight information construction methods, cartoons combined with turtles and presented with positive outcomes were the best way to communicate, i.e., cartoons showing animals in a friendly and positive way were the most effective form of marine garbage recycling for young people, and (2) Young people's preference for information will promote their self-efficacy in marine garbage recycling. The implications of these findings for developing marine protection information communication education for youth groups are also proposed.

A multi-targeting immunotherapy ameliorates multiple facets of Alzheimer's disease in 3xTg mice.

Alzheimer's disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aß-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aß and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aß and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aß and pTau in 3xTg transgenic mice. It significantly eradicated Aß plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aß and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.

[Clinical application of free peroneal artery leaflet perforator flap in postoperative complex defect of oral cancer].

Objective:To investigate the clinical effect of a segmented perforator flap of free peroneal artery to repair a complex defect after oral cancer. Methods:Forty-eight patients with oral cancer admitted to the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Bengbu Medical College from January 2018 to January 2022, including 8 of buccal cancer, 7 of floor cancer, 14 of tongue cancer, 5 of retromolar cancet, 9 of maxillary gingival cancer and 5 of mandibular gingival cancer. After lesion resection, 24 patients in the experimental group used the partial perforator flap to repair the defect, and 24 patients in the control group used the single flap to repair the defect. Compared with the general data of the two groups, the difference was not statistically significant（P>0.05）, which was comparable. The flap cutting range of the experimental group was 38.5-74.5 cm², and tension-reduced suture for the donor area. In the control group, the myocutaneous flap incision range was 61.0-76.5 cm², and skin graft suture for the donor area. Flap survival and patient survival were recorded and compared. The patients were followed up at 6 and 12 months after surgery, and their swallowing function and speech function, including the drinking water test, functional oral food intake scale and the Chinese language clarity test word table, were evaluated respectively, and their subjective satisfaction with the repair appearance was recorded. Patients in both groups were followed up for 12 to 60 months. Kaplan-Meier method was used to calculate the cumulative survival rate of patients, and survival curves were plotted. log-rank test was used to compare the survival curves between groups. Results:The survival rate of the two groups was 100%. The 5-year survival rate was 62.5% in the experimental group and 54.2% in the control group. There was no significant difference between the two groups （P>0.05）. According to the results of the functional recovery evaluation, the groups in swallowing and speech function and subjective satisfaction（P>0.05）, and at 12 months after surgery（P<0.05）. Conclusion:The segmented perforator flap of free peroneal artery is flexible and can repair different anatomical structures of postoperative composite defect of oral cancer, which can effectively improve postoperative functional recovery and patient satisfaction. Therefore, the peroneal artery segmented perforator flap is the ideal flap for reconstructing postoperative composite defect of oral cancer.

Ovotesticular disorder of sexual development manifested as hematospermia: a case report and literature review.

Background: Ovotesticular disorder of sexual development (OT-DSD) is a rare sexual development disorder defined by the simultaneous existence of testicular and ovarian tissues (including follicular) in the same- or opposite-sex glands of an individual, with an incidence rate of about 1 in 100 000. Aim: This report aims to supplement the clinical presentation, pathology, diagnosis, and treatment of OT-DSD and to improve the diagnostic ability of clinicians for modified disease. Methods: This article is a retrospective analysis of a case of OT-DSD at our institution. Additionally, a comprehensive search of the PubMed database with the keywords "ovotesticular disorder of sexual development" or "true hermaphroditism" was conducted between 1956 and 2024, resulting in approximately 250 cases, and the results of the search are summarized. Results: The patient, a 44-year-old male, sought treatment at our hospital on February 6, 2023, primarily due to "intermittent hematospermia for over a month." He stated that it was discovered during infancy that his right scrotum was empty and lacking a testicle. Due to the low local medical services and the low-income family's economic conditions, he did not seek further diagnosis and treatment. After admission, the patient underwent computed tomography and magnetic resonance imaging and decided to undergo robot-assisted pelvic mass resection, which was pathologically confirmed as OT-DSD. Outcomes: The patient's definitive diagnosis was provided by postoperative pathology, and although the patient ultimately had a favorable outcome, diagnosis and treatment were delayed due to his atypical clinical presentation. Strengths and Limitations: This is a single case report; however, uncommon clinical presentations of rare diseases were identified, and a literature review was conducted. Unfortunately, there are some important missing data in the patient's medical history, including hormone assessment (testosterone, luteinizing hormone, follicle-stimulating hormone), tumor marker examination, semen analysis, scrotal ultrasound, and chromosomal analysis. Conclusion: Patients with OT-DSD have diverse types of gonads, chromosomal karyotypes, and phenotypes of external genitalia, and further exploration and research are needed for early diagnosis and treatment. In addition, cases of OT-DSD with fertility and no ambiguous genitalia are even rarer. This case guides us for adult patients with no ambiguous genitalia: if there is an inability to palpate 1 or both gonads and there is intermittent hematospermia, the possibility of OT-DSD should be suspected.

Standardizing Attention Process Training-III for a Multisite Clinical Trial of Neuromodulation.

INTRODUCTION: The Control Network Neuromodulation to Enhance Cognitive Training in Complex Traumatic Brain Injury (CONNECT-TBI) study is an ongoing randomized, double-blinded, sham-controlled multisite clinical trial to determine the enhancing effects of noninvasive neuromodulation when paired with cognitive training in military participants (Veterans and active duty) with mild TBI. Attention Process Training-III (APT-III) was selected for its strong evidence base, manualized procedures, and computerized program. However, many aspects of APT-III that make it ideal for personalization make it less ideal for reliable implementation across participants, clinicians/technicians, and sites. The purpose of this feature article is to highlight APT-III procedures that require additional standardization for reliable administration across participants and sites. MATERIALS AND METHODS: Ten studies using APT-III were reviewed for methodology of APT-III administration. The manual was also scrutinized; aspects of administration that involved clinical decision-making, subjectivity, flexibility, and/or that were identified by the APT-III developers as areas in need of "empirical evaluation" were flagged by clinicians. Literature and manual review findings were presented to the team for discussion and solution-finding. The authors created and refined a standardized process that would allow participants to move through APT-III training, including task movement algorithms and new materials drafts. Refining of algorithms and drafts continued until there was a consensus from team members. RESULTS: Many gray areas were identified, but we will limit our reporting to focus on (1) dosage, (2) adaptation, (3) metacognitive strategy instruction, and (4) goal attainment scaling. We present APT-III manual details, literature review findings, and CONNECT-TBI decisions and materials for each of these areas of focus. CONCLUSIONS: We have highlighted some of the major gray areas of APT-III administration so that fellow researchers can understand the need to take similar steps in clinical trials using APT-III. We provide examples of our standardization process and resultant rules and materials. Our algorithm, based on prior studies using the APT-III and our own iterative adjustments, allows for adjustment of the difficulty and speed of the training tasks (but within certain parameters) in order to achieve the best balance between individualization and consistency across participants and sites. We provide an example of a workflow and reporting process for future studies.

Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury.

Hematopoietic stem cells (HSCs) employ a very unique metabolic pattern to maintain themselves, while the spectrum of their metabolic adaptations remains incompletely understood. Here, we uncover a distinct and heterogeneous serine metabolism within HSCs and identify mouse HSCs as a serine auxotroph whose maintenance relies on exogenous serine and the ensuing mitochondrial serine catabolism driven by the hydroxymethyltransferase 2 (SHMT2)-methylene-tetrahydrofolate dehydrogenase 2 (MTHFD2) axis. Mitochondrial serine catabolism primarily feeds NAD(P)H generation to maintain redox balance and thereby diminishes ferroptosis susceptibility of HSCs. Dietary serine deficiency, or genetic or pharmacological inhibition of the SHMT2-MTHFD2 axis, increases ferroptosis susceptibility of HSCs, leading to impaired maintenance of the HSC pool. Moreover, exogenous serine protects HSCs from irradiation-induced myelosuppressive injury by fueling mitochondrial serine catabolism to mitigate ferroptosis. These findings reframe the canonical view of serine from a nonessential amino acid to an essential niche metabolite for HSC pool maintenance.

Puff, the polytene chromosome: Visualizing transcription elongation control.

In this issue, Versluis et al.1 use a highly sensitive live-cell imaging system to examine transcription dynamics and functions of various key transcription elongation regulators at the Hsp70 loci.

The relationship between resistance evolution and carbon metabolism in Staphylococcus xylosus under ceftiofur sodium stress.

Staphylococcus xylosus has emerged as a bovine mastitis pathogen with increasing drug resistance, resulting in substantial economic impacts. This study utilized iTRAQ analysis to investigate the mechanisms driving resistance evolution in S. xylosus under ceftiofur sodium stress. Findings revealed notable variations in the expression of 143 proteins, particularly glycolysis-related proteins (TpiA, Eno, GlpD, Ldh) and peptidoglycan (PG) hydrolase Atl. Following the induction of ceftiofur sodium resistance in S. xylosus, the emergence of resistant strains displaying characteristics of small colony variants (SCVs) was observed. The transcript levels of TpiA, Eno, GlpD and Ldh were up-regulated, TCA cycle proteins (ICDH, MDH) and Atl were down-regulated, lactate content was increased, and NADH concentration was decreased in SCV compared to the wild strain. That indicates a potential role of carbon metabolism, specifically PG hydrolysis, glycolysis, and the TCA cycle, in the development of resistance to ceftiofur sodium in S. xylosus.

Maintaining H. pylori Negativity After Eradication Can Consolidate Its Benefit in Gastric Cancer Prevention: A Meta-Analysis.

INTRODUCTION: Several studies have reported the role of Helicobacter pylori eradication in gastric cancer (GC) prevention. However, for individuals with unsatisfactory management of their H. pylori infection status after eradication, the risk of GC remains unclear. METHODS: An exhaustive search strategy of the incidence of GC (including primary gastric cancer and metachronous gastric cancer) incidence in patients with unsuccessful eradication or H. pylori reinfection was implemented in the PubMed, Embase, Cochrane Library, and Web of Science. The hazard ratios (HRs) and cumulative incidence of total GC in patients with failed eradication or H. pylori reinfection (FE-Hp (+)) group were compared with that in patients with successful eradication and no H. pylori reinfection (SE-Hp (-)) group and patients with noneradication (NE) group. RESULTS: Seven eligible studies (including 8,767 patients with H. pylori infection) were identified. In the FE-Hp (+) group, the total GC risk was 1.86-fold of that in the SE-Hp (-) group (HR = 1.86, 95% confidence interval [CI]: 1.14-3.04, P = 0.013). The total GC risk in the NE group was also higher than that in the FE-Hp (+) group (HR = 1.98, 95% CI: 1.11-3.52, P = 0.002). On further analysis with different end points showed that the pooled GC risk increased over time (5-year follow-up: HR = 2.92, 1.34-6.34; 10-year follow-up: HR = 4.04, 2.56-6.37). DISCUSSION: Compared with the SE-Hp (-) group, the FE-Hp (+) group had a higher risk of gastric carcinoma. Long-term monitoring of H. pylori infection status could consolidate the benefit of eradicating H. pylori for preventing GC prevention in patients after eradication.

Research Progress of Biosensor Based on Organic Photoelectrochemical Transistor.

In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.