Generation of mitochondrial replacement monkeys by female pronucleus transfer.

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

Generation of the stable propagation Bessel beam and the axial multifoci beam with pure phase elements.

A recently proposed method is upgraded to convert two amplitude phase modulation systems (APMSs) to pure phase elements (PPEs), for generating the stable propagation Bessel beam and the axial multifoci beam, respectively. Phase functions of the PPEs are presented analytically. Numerical simulations by the complete Rayleigh-Sommerfeld method demonstrate that the converted PPE has implemented the same optical functionalities as the corresponding APMS, in either the longitudinal or the transverse direction. Compared with the traditional APMS, the converted PPE possesses many advantages such as fabrication process simplification, system complexity reduction, production cost conservation, alignment error avoidance, and experimental precision enhancement. These inherent advantages position the PPE as an ideal choice and driving force behind further advancements in optical system technology.

Design and Synthesis of Novel Diphenyl Ether Carboxamide Derivatives To Control the Phytopathogenic Fungus Sclerotinia sclerotiorum.

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus Sclerotinia sclerotiorum has led to serious losses in the yields of oilseed rape and other crops every year. Here, we designed and synthesized a series of carboxamide derivatives containing a diphenyl ether skeleton by adopting the scaffold splicing strategy. From the results of the mycelium growth inhibition experiment, inhibition rates of compounds 4j and 4i showed more than 80% to control S. sclerotiorum at a dose of 50 µg/mL, which is close to that of the positive control (flubeneteram, 95%). Then, the results of a structure-activity relationship study showed that the benzyl scaffold was very important for antifungal activity and that introducing a halogen atom on the benzyl ring would improve antifungal activity. Furthermore, the results of an in vitro activity test suggested that these novel compounds can inhibit the activity of succinate dehydrogenase (SDH), and the binding mode of 4j with SDH was basically similar to that of the flutolanil derivative. Morphological observation of mycelium revealed that compound 4j could cause a damage on the mycelial morphology and cell structure of S. sclerotiorum, resulting in inhibition of the growth of mycelia. Furthermore, in vivo antifungal activity assessment of 4j displayed a good control of S. sclerotiorum (>97%) with a result similar to that of the positive control at a concentration of 200 mg/L. Thus, the diphenyl ether carboxamide skeleton is a new starting point for the discovery of new SDH inhibitors and is worthy of further development.

Transcriptome analysis of axillary buds in low phosphorus stress and functional analysis of TaWRKY74s in wheat.

BACKGROUND: Wheat is one of the main grain crops in the world, and the tiller number is a key factor affecting the yield of wheat. Phosphorus is an essential element for tiller development in wheat. However, due to decreasing phosphorus content in soil, there has been increasing use of phosphorus fertilizer, while imposing risk of soil and water pollution. Hence, it is important to identify low phosphorus tolerance genes and utilize them for stress resistance breeding in wheat. RESULTS: We subjected the wheat variety Kenong 199 (KN199) to low phosphorus stress and observed a reduced tiller number. Using transcriptome analysis, we identified 1651 upregulated genes and 827 downregulated of genes after low phosphorus stress. The differentially expressed genes were found to be enriched in the enzyme activity regulation related to phosphorus, hormone signal transduction, and ion transmembrane transport. Furthermore, the transcription factor analysis revealed that TaWRKY74s were important for low phosphorus tolerance. TaWRKY74s have three alleles: TaWRKY74-A, TaWRKY74-B, and TaWRKY74-D, and they all belong to the WRKY family with conserved WRKYGQK motifs. These proteins were found to be located in the nucleus, and they were expressed in axillary meristem, shoot apical meristem(SAM), young leaves, leaf primordium, and spikelet primordium. The evolutionary tree showed that TaWRKY74s were closely related to OsWRKY74s in rice. Moreover, TaWRKY74s-RNAi transgenic plants displayed significantly fewer tillers compared to wild-type plants under normal conditions. Additionally, the tiller numebr of the RNAi transgenic plants was also significantly lower than that of the wild-type plants under low-phosphorus stress, and increased the decrease amplitude. This suggestd that TaWRKY74s are related to phosphorus response and can affect the tiller number of wheat. CONCLUSIONS: The results of this research showed that TaWRKY74s were key genes in wheat response to low phosphorus stress, which might regulate wheat tiller number through abscisic acid (ABA) and auxin signal transduction pathways. This research lays the foundation for further investigating the mechanism of TaWRKY74s in the low phosphorus environments and is significant for wheat stress resistance breeding.

Increased regional Hurst exponent reflects response inhibition related neural complexity alterations in pediatric bipolar disorder patients during an emotional Go-Nogo task.

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.

Ionotropic Receptor IR75q.2 Mediates Avoidance Reaction to Nonanoic Acid in the Fall Armyworm Spodoptera frugiperda (Lepidoptera, Noctuidae).

Ionotropic receptors (IRs) play an important role in olfaction, but little is known in nondrosophila insects. Here, we report in vitro and in vivo functional characterization of IR75q.2 in the invasive moth pest Spodoptera frugiperda. First, 13 IRs (including four coreceptor IRs) were found specifically or highly expressed in adult antennae. Second, these IRs were tested for responding profiles to 59 odorants using the Xenopus oocyte expression system, showing that only SfruIR75q.2 responded to 8-10C fatty acids and their corresponding aldehydes, with SfruIR8a as the only coreceptor. Third, the three acids (especially nonanoic acid) showed repellent effects on moth's behavior and oviposition, but the repellence significantly reduced to the insects with IR75q.2 knockout by CRISPR/Cas9. Taken together, our study reveals the function of SfruIR75q.2 in perception of acid and aldehyde odorants and provides the first in vivo evidence for olfactory function of an odor-specific IR in Lepidoptera.

Ideal suppression of Bessel beam intensity oscillations with a vortex phase plate.

We propose what we believe to be a new kind of diffractive phase element, i.e., vortex phase plate (VPP) with phase singularities along the azimuth direction. Phase function of the proposed VPP is given analytically. Axial intensity oscillations of propagating Bessel beams are ideally suppressed by using the proposed VPP. Compared with the traditional amplitude mask, the proposed VPP takes such advantages as a simpler fabrication procedure and a lower cost.

Generation of stable propagation Bessel beams and axial multifoci beams with binary amplitude filters.

The binary amplitude filter (BAF) is employed to generate stable propagation Bessel beams and axial multifoci beams, rather than the traditional continuous amplitude filter (CAF). We introduce a parameter along the azimuth direction, i.e., angular order of the BAF, to weaken transverse intensity asymmetry. Numerical simulations reveal that the BAF implements the same optical functionalities as the CAF. The BAF holds advantages over the traditional CAF: a simpler fabrication process, a lower cost, and a higher experimental accuracy. It is believed that the BAF should have many practical applications in future optical systems.

Laccase-Induced Gelation of Sugar Beet Pectin-Curcumin Nanocomplexes Enhanced by Genipin Crosslinking.

Research on the use of polysaccharides as hydrophobic bioactive carriers instead of proteins is still scarce. Sugar beet pectin (SBP) contains a small amount of protein and is a potential carrier for loading curcumin. In this work, SBP encapsulation, genipin crosslinking, and laccase-induced gelation were used to develop novel jelly food and improve the stability of curcumin without the incorporation of oil. By mixing the SBP solution (40 mg/mL) with curcumin powder (25 mg/mL SBP solution), an SBP-curcumin complex (SBP-Cur) was fabricated with a loading amount of 32 mg/g SBP, and the solubility of curcumin improved 116,000-fold. Fluorescence spectroscopy revealed that hydrophobic interactions drove the complexation of curcumin and SBP. Crosslinked by genipin (10 mM), SBP-Cur showed a dark blue color, and the gel strength of laccase-catalyzed gels was enhanced. Heating and UV radiation tests suggested that the genipin crosslinking and gelation strategies substantially improved the stability of curcumin. Because of the unique UV-blocking capacity of blue pigment, crosslinked samples retained 20% more curcumin than control samples. With the enhanced stability of curcumin, the crosslinked SBP-curcumin complexes could be a functional food ingredient used in functional drinks, baked food, and jelly food.

Nanocomposites of nitrogen-doped carbon dots/hydrotalcite with enhanced solid-state fluorescence for the recognition of latent fingerprints.

In this work, a green emissive nanocomposite was synthesized by embedding nitrogen-doped carbon dots into hydrotalcite (N-CD/hydrotalcite) via a hydrothermal process for the recognition of latent fingerprints (LFPs). Good dispersion of the nano-sized N-CD on the surface of hydrotalcite overcomes the fluorescence quenching of N-CD in the solid state and can enhance solid-state fluorescence. N-CD/hydrotalcite emits stable strong green fluorescence even at different excitation wavelengths and exhibits good selectivity and sensitivity for the visualization of LFPs on various substrates such as glass slides, tiles, leather, aluminum foil, printing paper, colored surfaces of plastic packing, copper foil, planks, leaves, currencies, and bar codes. The high-level details of the ridge patterns of both fresh and aged LFPs can be clearly identified with good clarity and high contrast without background interferences under the excitation of a 450 nm light source. There is no significant difference in the LFP image visualized by N-CD/hydrotalcite and commercial fluorescent powders, indicating that the effectiveness of N-CD/hydrotalcite for the visualization of LFPs is equivalent to that of commercial fluorescent powders. These observations illustrate that N-CD/hydrotalcite has great potential in the recognition of LFPs.

Immune checkpoint inhibitor-related adverse cardiac events in patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: Although people are more and more aware of the cardiotoxicity caused by immune checkpoint inhibitors (ICIs) in the treatment of lung cancer, its incidence rate has not been systematically analyzed. This study aims to evaluate the incidence of cardiotoxicity related to the ICI therapies for lung cancer, so as to enhance clinicians' attention to cardiotoxicity, implement proper prevention and intervention for high-risk patients, and minimize the risk of cardiac dysfunction during and after completion of therapy. METHODS: We conducted a systematic literature search for relevant publications in PubMed and Scopus from inception to 19 April 2022. Pooled incidence and risk ratios with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated. RESULTS: A total of 37 studies covering 38 trials, including 14,342 patients, were identified. The pooled risk ratios of incidence of any cardiac AEs were 1.944 [95% CI 0.8-4.725] (Single ICI versus chemotherapy), 1.677 [95% CI 1.065-2.64] (Single ICI plus chemotherapy versus chemotherapy), and 0.478 [95% CI 0.127-1.798] (Single ICI versus Dual ICI). The incidence of myocarditis and arrhythmia were 0.003[95%CI 0.002-0.006] and 0.014[95%CI 0-0.037], respectively. CONCLUSION: Single ICI did not increase the risk of cardiotoxicity compared with chemotherapy, and single ICI plus chemotherapy increased the risk of cardiotoxicity by 67% compared with chemotherapy alone. Combination immunotherapy did not increase the risk of cardiotoxicity compared with single ICI.

In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder.

BACKGROUND: Diabetes is a metabolic disease with a high complication rate. Diabetic foot ulcers (DFUs) seriously affect the quality of life of patients. A total of 15%-20% of diabetic patients develop DFUs, which heal with difficulty over a long time and can result in amputation and disability. Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases. Ruyi Jinhuang powder (RHP) is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice. AIM: To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin (HE) staining. The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry (GC-MS), and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism. METHODS: Sprague Dawley rats were injected with streptozotocin to establish the DFU model. HE staining was used to observe the wound tissue under an electron microscope. The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction, and then, GC-MS and ultra-performance liquid chromatography-MS were used to separately identify the chemical constituents. In addition, the "herb-component-target" link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information, and the molecular docking of important components and key targets was performed in Discovery Studio software. Cytoscape software was used to visualize and analyze the relationship between the chemical composition, targets and Traditional Chinese Medicine network. RESULTS: RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells. A total of 89 chemical components were obtained by GC-MS. Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU, of which the important components were luteolin, trans caryophyllene, ar-turmerone, palmitic acid, methyl palmitate, gallic acid, demethoxycurcumin, berberine, and rheic acid. The key targets were posttranscriptional silencing, topoisomerase II alpha, muscarinic acetylcholine receptor M2, interleukin 6, tumor necrosis factor and retinoic X receptor alpha, and the key pathways were the phosphoinositide 3-kinase-protein kinase B signaling pathway, neuroactive ligand-receptor interactions, and the forkhead box O signaling pathway. CONCLUSION: Our results indicated that RHP may play a role in the treatment of DFU through these target pathways by affecting insulin resistance, altering the nervous system and immune system, participating in inflammatory responses and regulating cell proliferation, differentiation and apoptosis through other specific mechanisms.

Clinical Features of Central Retinal Vein Occlusion in Young Patients.

Retinal vein occlusion (RVO) is the second most common retinal vascular disease. Central RVO (CRVO), in which obstruction occurs posterior to the lamina cribrosa due to various causes, manifests with extensive venous tortuosity, dilatation of blood vessels in the four quadrants, and retinal hemorrhage. The presence of macular edema decreases visual acuity in patients with CRVO, especially in elderly patients with hypertension, hyperlipidemia, and diabetes. In the last decade, treatment modalities for CRVO have improved, with anti-vascular endothelial growth factor agents being widely used as treatment. However, there are cases of refractory or recurrent macular edema. Moreover, CRVO also occurs in young patients. This article reviews previous studies and case reports and summarizes the differences in etiological factors, clinical manifestations, treatment, and prognosis between young and elderly patients. Due to the low incidence of CRVO in young patients, clinical data from these age groups are limited. Hence, further studies are warranted to explore the differences between age groups to improve individualization of treatment of young patients.

[ZHANG Wei-hua's experience in clinical treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture].

The clinical experience in treatment of somatalgia with "point-zone-strip stimulation technique" of acupuncture of professor ZHANG Wei-hua was summarized. Professor ZHANG integrates the theories of the cutaneous region of meridian, biaoben, "taking tender point as acupoint" and local holography as a whole in treatment of somatalgia. The "point-stimulation technique" of acupuncture (subcutaneous needling technique) is adopted for the painful site less than 3 cm in diameter, the "zone-stimulation technique" (surrounding needling technique) is for the site larger than 3 cm in diameter and the "strip-stimulation technique" (cubit-tibia needling technique) is for various acute and chronic somatalgia. These three needling techniques are applicable singly or in combination in clinical practice.

Helicid Reverses the Effect of Overexpressing NCALD, Which Blocks the sGC/cGMP/PKG Signaling Pathway in the CUMS-Induced Rat Model.

Background: Increasing evidence has shown that apoptosis in the hippocampus is closely related to depressive-like behavior. We previously reported that helicid had good antidepressant activities, which manifested as the alleviation of depression-like behaviors and the reversal of the high expression of neurocalcin delta (NCALD) in chronic unpredictable mild stress (CUMS) rats. The aim of this study was, therefore, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing NCALD and using rescue experiments. Methods: We developed the CUMS rat model using CUMS stimulation from week 0 to week 6. The rats were treated with helicid, or NCALD silenced, then we overexpressed NCALD using adeno-associated virus. We also measured the protein levels of sGCα1, sGCß1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA. Results: Treating CUMS rats by silencing NCALD or by the administration of helicid improved the depressive-like behavior. The levels of proteins, including sGC, PKG, cleaved caspase-3, and cGMP, in hippocampus all decreased. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Limitation. We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied. Conclusions: Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration.

Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A 'One size fits all' approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. METHODS: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. RESULTS: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/µl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/µl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/µl. CONCLUSION: Our research shows that a BEC ⩾ 200 cells/µl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.

Antidepressant-like effects of helicid on a chronic unpredictable mild stress-induced depression rat model: Inhibiting the IKK/IκBα/NF-κB pathway through NCALD to reduce inflammation.

We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.

Diversity and Distribution of Anaerobic Ammonium Oxidation Bacteria in Hot Springs of Conghua, China.

Anaerobic ammonium oxidation (anammox) is an important process of the nitrogen cycle, and the anammox bacteria have been studied in a wide variety of environments. However, the distribution, diversity, and abundance of anammox bacteria in hot springs remain enigmatic. In this study, the anammox process was firstly investigated in hot springs of Conghua, China. Anammox-like bacterial sequences that closely affiliated to "Candidatus Brocadia," "Candidatus Kuenenia," "Candidatus Scalindua," "Candidatus Anammoxoglobus," and "Candidatus Jettenia" were detected. Several operational taxonomic units (OTUs) from this study shared low sequence identities to the 16S rRNA gene of the known anammox bacteria, suggesting that they might be representing putative novel anammox bacteria. A quantitative PCR analysis of anammox-specific 16S rRNA gene confirmed that the abundance of anammox bacteria ranged from 1.60 × 104 to 1.20 × 107 copies L-1. Nitrate was a key environmental factor defining the geographical distribution of the anammox bacterial community in the hot spring ecosystem. Dissolved inorganic carbon had a significant influence on anammox bacterial biodiversity. Our findings for the first time revealed that the diverse anammox bacteria, including putative novel anammox bacterial candidates, were present in Conghua hot spring, which extended the existence of anammox bacteria to the hot springs in China and expands our knowledge of the biogeography of anammox bacteria. This work filled up the research lacuna of anammox bacteria in Chinese hot spring habitat and would guide for enrichment strategies of anammox bacteria of Conghua hot springs.