Integrated Transcriptomic and Proteomic Characterization of a Chromosome Segment Substitution Line Reveals the Regulatory Mechanism Controlling the Seed Weight in Soybean.

Soybean is the major global source of edible oils and vegetable proteins. Seed size and weight are crucial traits determining the soybean yield. Understanding the molecular regulatory mechanism underlying the seed weight and size is helpful for improving soybean genetic breeding. The molecular regulatory pathways controlling the seed weight and size were investigated in this study. The 100-seed weight, seed length, seed width, and seed weight per plant of a chromosome segment substitution line (CSSL) R217 increased compared with those of its recurrent parent 'Suinong14' (SN14). Transcriptomic and proteomic analyses of R217 and SN14 were performed at the seed developmental stages S15 and S20. In total, 2643 differentially expressed genes (DEGs) and 208 differentially accumulated proteins (DAPs) were detected at S15, and 1943 DEGs and 1248 DAPs were detected at S20. Furthermore, integrated transcriptomic and proteomic analyses revealed that mitogen-activated protein kinase signaling and cell wall biosynthesis and modification were potential pathways associated with seed weight and size control. Finally, 59 candidate genes that might control seed weight and size were identified. Among them, 25 genes were located on the substituted segments of R217. Two critical pathways controlling seed weight were uncovered in our work. These findings provided new insights into the seed weight-related regulatory network in soybean.

Impact of Refractive Status on Presbyopia Progression among Patients with Presbyopia.

PURPOSE: To explore the impact of refractive status on presbyopia progression among patients with presbyopia. METHODS: This retrospective observational study included patients with presbyopia who visited the Seventh Affiliated Hospital of Sun Yat-sen University and Shenzhen Polytechnic Medical College between May 2018 and August 2022. The amplitude of accommodation (AMP) and near addition power (ADD) at 6 months and 1 year were collected. RESULTS: A total of 103 patients with presbyopia were included in this study: 42 patients with myopia, 23 patients with emmetropia, and 38 patients with hyperopia. There were significant differences in ΔAMP(6-month) and ΔADD(6-month) among patients with different refractive statuses, and the values of emmetropic patients and hyperopic patients were higher than in myopic patients (all P < 0.001). The ΔAMP(1-year) and ΔADD(1-year) of hyperopic patients were significantly higher than in emmetropic patients and myopic patients (all P < 0.001). The ΔADD(1-year) of emmetropic patients was greater than in myopic patients (P = 0.045), but there were no significant differences in ΔAMP(1-year) between patients with emmetropia and myopia (P = 0.090). CONCLUSIONS: The progression of presbyopia in hyperopic patients was relatively more significant than for emmetropia, followed by myopia. The prescription of presbyopia glasses might need to be replaced more frequently in patients with hyperopia.

Analysis of related factors for neuropsychiatric comorbidities in children with epilepsy.

OBJECTIVE: To analyze the risk factors affecting psychiatric behavior and study the psychobehavioral conditions of children with epilepsy. METHOD: We randomly selected and enrolled 294 children with epilepsy who visited and were hospitalized in the pediatric clinic of Hebei General Hospital between January 2017 and January 2022, as the study participants. We comprehensively assessed their cognitive functions using the Gesell development schedule or Wechsler Intelligence Scales. The participants were divided into the study group (n = 123) with cognitive impairment and the control group (n = 171) with normal cognitive functions, for analysis. RESULTS: There were statistically significant differences between the two groups in disease course, frequency of epilepsy, status epilepticus, and the number of antiseizure medications (ASMs) used (P < 0.05), while there were no statistically significant differences in age, gender, age of onset, form of onset, interictal epileptiform discharge, history of febrile convulsion, and the time from onset to initial visit (P > 0.05). Based on multivariate logistic regression analysis, the course of disease, frequency of onset, status epilepticus and number of ASMs used were identified as high-risk factors for cognitive impairment in children with epilepsy. Similarly, early onset, long course of disease, known etiology, and combination of multiple drugs have a negative impact on behavioral problems, school education, and social adaptability. CONCLUSION: The course of disease, the frequency of onset, status epilepticus, and the number of ASMs used are high-risk factors for cognitive impairment in children with epilepsy, which can be prevented and controlled early. When selecting ASMs, their advantages and disadvantages should be weighed. Moreover, the availability of alternative treatment options must be considered. With the help of genomic technology, the causes of epilepsy should be identified as early as possible, and precision medicine and gene therapy for children with epilepsy should be actively developed.

Qudit-based high-dimensional controlled-not gate.

High-dimensional quantum systems expand quantum channel capacity and information storage space. By implementing high-dimensional quantum logic gates, the speed of quantum computing can be practically enhanced. We propose a deterministic 4 × 4-dimensional controlled-not (CNOT) gate for a hybrid system without ancillary qudits required, where the spatial and polarization states of a single photon serve as a control qudit of four dimensions, whereas two electron-spin states in nitrogen-vacancy (NV) centers act as a four-dimensional target qudit. As the control qudits are easily operated employing simple optical elements and the target qudits are available for storage, the CNOT gate works in a deterministic way, and it can be flexibly extended to n × n-dimensional (n > 4) quantum gates for other hybrid systems or different photonic degrees of freedoms. The efficiency and fidelity of the CNOT gate are analyzed aligning with current technological capabilities, finding that they have satisfactory performances.

Decoherence-free-subspace-based deterministic conversions for entangled states with heralded robust-fidelity quantum gates.

The decoherence-free subspace (DFS) serves as a protective shield against certain types of environmental noise, allowing the system to remain coherent for extended periods of time. In this paper, we propose two protocols, i.e., one converts two-logic-qubit Knill-Laflamme-Milburn (KLM) state to two-logic-qubit Bell states, and the other converts three-logic-qubit KLM state to three-logic-qubit Greenberger-Horne-Zeilinger states, through cavity-assisted interaction in DFS. Especially, our innovative protocols achieve their objectives in a heralded way, thus enhancing experimental accessibility. Moreover, single photon detectors are incorporated into the setup, which can predict potential failures and ensure seamless interaction between the nitrogen-vacancy center and photons. Rigorous analyses and evaluations of two schemes demonstrate their abilities to achieve near-unit fidelities in principle and exceptional efficiencies. Further, our protocols offer progressive solutions to the challenges posed by decoherence, providing a pathway towards practical quantum technologies.

N-aminomorpholine-functionalized bromine-doped carbon dots for hypochlorous acid detection in foods and imaging in live cells.

Hypochlorous acid (HClO) is used in food preservation. However, excessive HClO can deteriorate nutritional composition of food, compromise its quality, and potentially induce various diseases. Consequently, the development of multifunctional fluorescent probes for the sensitive and selective detection of HClO is highly anticipated for food safety. In this work, we designed a nanoprobe using N-aminomorpholine (AM)-functionalized bromine-doped carbon dots (Br-CDs-AM) for sensing HClO. This nanoprobe exhibits pH stability, strong resistance to photobleaching, superior long-term photostability (12 weeks), high sensitivity (19.3 nM), and an ultrarapid response (8 s) for detecting HClO residues in food matrices with percentage recovery (96.5 %-108 %) and RSDs less than 5.34 %. In addition, extremely low cytotoxicity and outstanding biocompatibility enable the nanoprobe to be used primarily for lysosome tracking and rapidly visualizing HClO in live cells. Thus, this study provides a new pathway to design unconventional nanoprobes for food safety assessment and subcellular organelle-specific imaging HClO.

Bismuth, Nitrogen-Codoped Carbon Dots as a Dual-Read Optical Sensing Platform for Highly Sensitive, Ultrarapid, Ratiometric Detection of Doxorubicin.

Doxorubicin (DOX) is a potent anticancer drug, but it has side effects on normal tissues, particularly myocardial cells. Therefore, it is crucial to detect the DOX concentration in body fluids for effective clinical treatment. In this work, N,Bi-codoped CDs (Bi,N-CDs) were synthesized through a one-step hydrothermal method to carbonize the raw materials of 2,4-dinitroaniline and bismuth nitrate. The resulting Bi,N-CDs showed a reduced emission at 490 nm and an enhanced emission at 590 nm in the presence of DOX. The ratio of fluorescence (FL) intensity (F590/F490) was found to be a reliable indicator of DOX concentration, ranging from 0.05 to 30 µM and 40-200 µM, with detection limits (LOD) of 34 and 24 nM, respectively. A ratiometric fluorescence nanoprobe was established for highly selective and sensitive detection of DOX using a specific electrostatic interaction and inner filter effect between Bi,N-CDs and DOX. Meanwhile, Bi,N-CDs exhibited a distinct color change ranging from yellow to orange-red when exposed to DOX, allowing for a colorimetric method to measure DOX levels in the range of 0.05-30 µM, with a detection limit of 169 nM. The probe was triumphantly used to monitor DOX in actual samples via a dual-mode optical sensing strategy. This study contributes to the development of heteroatom-doped CDs and expands their potential applications for detecting biological samples.

Synthetic strategies, properties and sensing application of multicolor carbon dots: recent advances and future challenges.

Recently, carbon dots (CDs) as newly developed carbon-based nanomaterials due to advantages such as excellent photostability and easy surface functionalization have generated wide application prospects in fields such as biological imaging and chemical sensing. The multicolor emission carbon dots (M-CDs) were acquired through the selection of different carbon source precursors, change of synthesis conditions and synthesis environment. Therefore, the aim of this review is to summarize the latest research progress in polychromatic CDs from the perspectives of synthesis strategies, luminescent mechanisms, luminescent properties and applications. This review focuses on how to prepare MCDs by changing raw materials and synthesis conditions such as reaction temperature, synthesis time, synthesis pH, and synthesis solvent. This review also presents the optical properties of MCDs, concentration effects, solvent effects, pH effects, elemental doping, and surface passivation on them, as well as their creative applications in the field of sensing applications. It is anticipated that this review will serve as a guide for the development of multifunctional M-CDs and inspire future research on controllable design and preparation of M-CDs.

Aggregation enhanced FRET: A simple but efficient strategy for the ratiometric detection of uranyl ion.

Uranium is one of the most important radionuclides but could also cause potential health risks to human beings due to its radioactive and chemical toxicity. It is an urgent task to develop a simple but efficient sensing platform for UO22+, the main existing form of uranium in environment. Herein, a rhodamine-functionalized carbon dots (o-CDs-Rho) was synthesized and applied for UO22+ sensing through a simple but novel aggregation-enhanced FRET strategy. The weak FRET efficiency (16.2%) of o-CDs-Rho in dispersed solution is significantly enhanced (>77.2%) after UO22+ triggered aggregation due to the increased number of rhodamine acceptors around each CDs from dispersed 80 to aggregated 2800. This is the first ratiometric fluorescence sensor with an inverse change of fluorescence intensity at dual emission wavelengths under single-wavelength excitation for UO22+. Under optimized experiment conditions, o-CDs-Rho nanosensor shows a low detection limit of 53 nM and excellent selectivity. Meanwhile, the as-prepared nanosensor also shows high reliability and stability. These excellent properties make it successful in detecting uranium content in real samples.

Sequence and expression regulation of the BCL2L2 gene in pigs.

B cell lymphoma-2-like 2 (BCL2L2), an important regulator of apoptosis, plays vital roles in several physiological processes, as revealed by studies in humans and mice. However, reports on pig BCL2L2 are few, and the encoding gene has not been identified experimentally. This study was designed to clone the porcine BCL2L2 gene and its alternative splicing (AS) transcripts using molecular biological techniques and to analyze the regulatory mechanisms underlying transcription and translation. The BCL2L2 cDNA (V1) was 807 bp in length and encoded a polypeptide of 193 aa containing four BCL-2 homology domains. A total of nine AS transcripts were obtained, among which V2 and V3 differed from V1 in the 5' untranslated region (UTR). The core promoter was mapped to a range of -1102 to -759 bp (the first nucleotide of the start codon was designated as +1). There were several functional cis-elements, including one SP1 and two C/EBPα binding sites at around -759 bp. AS in the 5' UTR is involved in the regulation of gene expression, as revealed by dual-luciferase reporter and western blot analysis, and the secondary structure of the 5' UTRs may be the reason for the differential expression of V1-3. At the same time, an upstream open reading frame (ORF) existed in each of the three 5' UTRs, was found to repress the expression of the main ORF. Additionally, the roles of porcine BCL2L2 in cell proliferation and apoptosis were preliminarily analyzed. The results will contribute to further characterizing the role of BCL2L2.

Nitrogen doped biomass derived carbon dots as a fluorescence dual-mode sensing platform for detection of tetracyclines in biological and food samples.

Nitrogen-doped carbon dots (N-CDs) were synthesized hydrothermally using abundantly accessible pitaya peel and 1,2-ethylenediamine as precursors. N-CDs exhibited favorable photostability, which can serve as a multifunctional nano-sensor for detection of three tetracycline antibiotics (TCs) based on fluorescence (FL) dual-mode sensing strategy. The FL intensity of N-CDs could be rapidly quenched by tetracycline (TC) and oxytetracycline (OTC) based on bandgap transition, inner filter effect (IFE), static quenching (SQ) and electrostatic interaction. While a new finding that FL of N-CDs demonstrated a remarkable enhancement in the presence of chlortetracycline (CTC) with the same detection mechanisms as TC and OTC, also including the aggregation-induced emission (AIE). Furthermore, an easily extensible fluorescence sensor array was developed based on multiple CDs for identifying multiple TCs in real samples. Therefore, the constructed N-CDs provides a new perspective for choosing extensive natural biomass to synthesize CDs, further developing a novel sensor to realize their versatile sensing application.

Erratum: A2780 human ovarian cancer cells with acquired paclitaxel resistance display cancer stem cell properties.

[This corrects the article DOI: 10.3892/ol.2013.1568.].

A novel carbon-nanodots-based theranostic nano-drug delivery system for mitochondria-targeted imaging and glutathione-activated delivering camptothecin.

Chemotherapy is severely limited by continuously decreased therapeutic efficacy and uncontrolled side effects on normal tissue, which can be improved by constructing a nanoparticle-based drug delivery system (DDS). Nevertheless, no studies have reported on DDS-based on carbon-nanodots (CNDs), combining subcellular organelle-targeted imaging/drug delivery, high drug loading content, and glutathione (GSH)-sensitive drug release into one system. Herein, the as-fabricated CNDs can be covalently conjugated with a mitochondria-targeting ligand (triphenylphosphine, TPP), a smart GSH-responsive disulfide linker (S-S), and the anticancer drug (camptothecin, CPT) to initially prepare a theranostic nano-DDS (TPP-CNDs-S-CPT) with the drug loading efficiency of 64.6 wt%. Owing to excellent water dispersibility, superior fluorescence properties, satisfactory cell permeability, and favorable biocompatibility, TPP-CNDs-S-CPT was successfully used for intracellular mitochondrial-targeted imaging in vitro. High intracellular GSH concentrations in tumor cells caused the cleavage of S-S, resulting in concomitant activation and release of CPT, as well as significant fluorescence enhancement. In vivo, TPP-CNDs-S-CPT exhibited lower biological toxicity and even higher tumor-activatable performance than free CPT, as well as specific cancer therapy with few side effects. The mitochondria-targeted ability and the precise drug-release in tumor make TPP-CNDs-S-CPT a hopeful chemotherapy prodrug, providing significant theoretical basis and data support for in-depth understanding and exploration of chemotherapeutic DDS-based on CNDs.

Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1.

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA <40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96. The incidence of PDVF was as expected in this difficult-to-treat patient population and, among RC participants, was comparable regardless of the presence of predefined gp120 amino acid substitutions that potentially influence phenotypic susceptibility to temsavir (S375H/I/M/N/T, M426L, M434I, M475I) or baseline temsavir 50% inhibitory concentration fold change (IC50 FC). The incidence of PDVF was lower among participants with higher overall susceptibility score to newly used antiretrovirals (OSS-new), indicating that OSS-new may be a preferred predictor of virologic outcome in heavily treatment-experienced individuals. Predefined gp120 substitutions, most commonly M426L or S375N, were emergent on treatment in 24/50 (48%) RC and 33/44 (75%) NRC participants with PDVF, with related increases in temsavir IC50 FC. In BRIGHTE, PDVF was not consistently associated with treatment-emergent genotypic or phenotypic changes in susceptibility to temsavir or to antiretrovirals in the initial OBT. Further research will be needed to identify which factors are most likely to contribute to virologic failure in this heavily treatment-experienced population (ClinicalTrials.gov, NCT02362503).

Changes in Retinal Vessel Flow after Small Incision Lenticule Extraction.

Objective: In order to analyze changes in retinal vessel flow after small incision lenticule extraction (SMILE). Methods: A total of 32 patients (62 eyes) who underwent SMILE were enrolled in this prospective study. Optical parameters, including vessel density (VD), and perfusion density (PD) of foveal, parafoveal, and perifoveal regions, respectively, were measured before surgery and at 1 day, 1 week, 1 month, and 3 months postoperation. Preoperative parameters and surgical parameters were recorded. Results: Significant decreases in VD and PD on postoperative day 1 were detected in all quadrants, both in 3 mm and in 6 mm regions (P < 0.001). One month after surgery, VD returned to preoperative levels. None of the preoperative and surgical parameters were significantly correlated with the VD and PD fluctuations (all P > 0.05). Conclusion. VD may decrease significantly with regional disparity 1 day after SMILE while recovering at 1 month. Elevation of intraocular pressure due to suction may account for such changes.

Treatment of MGMT promoter unmethylated glioblastoma with PD-1 inhibitor combined with anti-angiogenesis and epidermal growth factor receptor tyrosine kinase inhibitor: a case report.

Glioblastoma (GBM) is the most common primary central nervous system (CNS) malignancy in adults and is associated with poor prognosis, especially even worse in those with unmethylated MGMT promoter. Currently, maximal safe resection combined with temozolomide (TMZ) concurrent chemoradiotherapy and TMZ adjuvant chemotherapy has been considered the standard treatment for newly diagnosed GBM. The efficacy of drugs other than TMZ is currently undefined. With increasing understanding of the biological characteristics of GBM, more and more studies are being conducted on drug targets, such as specific signaling pathways and microenvironment. Herein, we report the case of a GBM patient with unmethylated MGMT promoter who was intolerant to TMZ, and underwent treatment with the combination of carelizumab, anlotinib, and oxitinib during radiotherapy according to results of whole-exome sequencing (WES) and the patient's condition. The progression-free survival (PFS) and overall survival (OS) for this case were respectively nearly 11 and 18 months, significantly exceeding the historical data and the tolerance of the treatment for this case without sever adverse effects was favorable. Our case provides clinical evidence supporting the efficacy of the above three drugs and radiotherapy, which may translate into novel individualized treatment strategies for GBM patients who are intolerant to TMZ.

Tumor treating fields combined with a poly (adenosine diphosphate-ribose) polymerase inhibitor during radiotherapy for rapidly progressing IDH-wildtype diffuse astrocytoma: a case report.

A 57-year-old woman was diagnosed with IDH-wildtype (IDHwt) astrocytoma (World Health Organization grade II) with the molecular characteristics of glioblastoma. She underwent concurrent radiotherapy and chemotherapy according to the Stupp protocol in combination with a multi-target antiangiogenic drug and additional intrathecal chemotherapy using methotrexate. During treatment, the patient's tumor showed rapid progression. The chemotherapy with temozolomide was stopped and replaced with radiotherapy combined with tumor treating fields (TTF), the poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib, and anlotinib. After the radiotherapy was completed, the symptoms of increased intracranial pressure and epilepsy were well controlled. Considering the patient's tolerance to the treatment, the combined therapy of TTF and anlotinib was continued, and osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor with good permeability of the blood-brain barrier, was added. The patient was regularly followed up and had no obvious adverse drug reactions. Head magnetic resonance imaging (plain scan + enhanced scan) suggested that the lesions were stable. For rapidly progressing glioblastomas or histological grade II/III IDHwt astrocytomas, the combination of TTF and a PARP inhibitor during radiotherapy may have a synergistic effect on tumor control and is well tolerated by patients.

N-Doped carbon dots for the fluorescence and colorimetry dual-mode detection of curcumin.

Nitrogen doped carbon dots (N-CDs) were synthesized by a one-step hydrothermal method with dopamine and ethylenediamine. The as-prepared N-CDs were characterized via transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), fluorescence spectrophotometer, UV-Vis spectrophotometry and Fourier transform infrared spectroscopy (FTIR). The average particle dimension of the as-prepared N-CDs was 2.68 nm, and the best excitation and emission wavelengths were 405 nm and 535 nm, separately. N-CDs exhibits excellent selectivity and sensitivity to detect the curcumin (Cur), attaining a wider linear range of 97.5 nM-67.9 µM and a limit of detection (LOD) of as low as 94 nM. Interestingly, N-CDs can also give responsive signals of a visible colour change (yellow to red). Moreover, a novel fluorescent/colorimetric dual-mode method has been successfully employed for the determination of Cur in real samples with good recoveries (94%-110%) and precision (RSD = 0.3-2.9%).

Carbon dots for ratiometric fluorescence detection of morin.

The B,N dual-doped carbon dots (B,N-CDs) for ratiometric fluorescence detection the morin were prepared from sodium tetraborate and polyethyleneimine through the single-step hydrothermal method. The B,N-CDs exhibited the optimum excitation and emission wavelength at 340 nm and 467 nm, respectively. Interestingly, the intensities of emission peak at 467 nm of B,N-CDs reduced meanwhile a new peak emerged at 560 nm with the continuous addition of morin, which revealed the ratio fluorescence characteristic between F560nm/F467nm and morin concentration with the linearity range and detection limit of 14.5-32.5 µmol/L and 0.3 µmol/L (S/N = 3), respectively. The interference of common antibiotics and remedies could be ignored when the concentration of morin was detected by the B,N-CDs, which demonstrating the outstanding selectivity. Furthermore, the proposed fluorescence method is used to detect morin in urine with recoveries are 99.8-104.5%. The results of this research indicate the feasibility and practicality of B,N-CDs as an effective fluorescent probe for the determination of morin.

Carbon Nanodots as a Multifunctional Fluorescent Sensing Platform for Ratiometric Determination of Vitamin B2 and "Turn-Off" Detection of pH.

In this work, we synthesized carbon nanodots (CNDs) by a one-pot hydrothermal method to carbonize precursors of dry carnation petals and polyethylenimine. The obtained CNDs possess favorable photostability, good biocompatibility, and excellent water solubility, which can serve as a dual-responsive nanosensor for the determination of vitamin B2 (VB2) and pH. A unique ratiometric fluorescence resonance energy transfer probe was developed through a strong interaction between VB2 and surface moieties of CNDs. CNDs emitted at 470 nm; however, in the presence of VB2, an enhanced emission peak was clearly observed at 532 nm. The value of I532/I470 exhibits a stable response to the VB2 concentration from 0.35 to 35.9 µM with a detection limit of 37.2 nM, which has been used for VB2 detection in food and medicine samples and ratiometric imaging of VB2 in living cells with satisfying performance. In addition, the proposed CNDs also displayed pH-sensitive behavior and can be a turn-off fluorescent sensor to monitor pH. The fluorescent intensity at 470 nm is a good linear response against pH values from 3.6 to 8, affording the capability as a single-emissive nanoprobe for intracellular pH sensing.