DOT1L decelerates the development of osteoporosis by inhibiting SRSF1 transcriptional activity via microRNA-181-mediated KAT2B inhibition.

OBJECTIVE: Our study explored the function of DOT1L in osteoporosis (OP) via the microRNA (miR)-181/KAT2B/SRSF1 axis. METHODS: Osteoclast (OC) number was evaluated via TRAP staining, and serum CTXI, PINP, and ALP contents were tested by ELISA. Following identification of bone marrow mesenchymal stem cells (BMSCs), OC differentiation was induced by M-CSF and RANKL, followed by the detection of OC differentiation and the expression of bone resorption-related genes, DOT1L, miR-181, KAT2B, and SRSF1. RESULTS: Overexpressed DOT1L or miR-181 stimulated calcified nodule formation and increased alkaline phosphatase activity and osteogenic marker gene expression. KAT2B knockdown enhanced the osteogenic differentiation of BMSCs by reducing SRSF1 acetylation. The enhancement of OC differentiation induced by overexpressed SRSF1 was inhibited by simultaneous DOT1L or miR-181 overexpression. DOT1L suppressed OP development in vivo via the miR-181/KAT2B/SRSF1 axis. CONCLUSION: DOT1L overexpression slowed down bone loss and promoted bone formation via the miR-181/KAT2B/SRSF1 axis, thereby alleviating OP development.

A higher-yield hybrid rice is achieved by assimilating a dominant heterotic gene in inbred parental lines.

The exploitation of heterosis to integrate parental advantages is one of the fastest and most efficient ways of rice breeding. The genomic architecture of heterosis suggests that the grain yield is strongly correlated with the accumulation of numerous rare superior alleles with positive dominance. However, the improvements in yield of hybrid rice have shown a slowdown or even plateaued due to the limited availability of complementary superior alleles. In this study, we achieved a considerable increase in grain yield of restorer lines by inducing an alternative splicing event in a heterosis gene OsMADS1 through CRISPR-Cas9, which accounted for approximately 34.1%-47.5% of yield advantage over their corresponding inbred rice cultivars. To achieve a higher yield in hybrid rice, we crossed the gene-edited restorer parents harbouring OsMADS1GW3p6 with the sterile lines to develop new rice hybrids. In two-line hybrid rice Guang-liang-you 676 (GLY676), the yield of modified hybrids carrying the homozygous heterosis gene OsMADS1GW3p6 significantly exceeded that of the original hybrids with heterozygous OsMADS1. Similarly, the gene-modified F1 hybrids with heterozygous OsMADS1GW3p6 increased grain yield by over 3.4% compared to the three-line hybrid rice Quan-you-si-miao (QYSM) with the homozygous genotype of OsMADS1. Our study highlighted the great potential in increasing the grain yield of hybrid rice by pyramiding a single heterosis gene via CRISPR-Cas9. Furthermore, these results demonstrated that the incomplete dominance of heterosis genes played a major role in yield-related heterosis and provided a promising strategy for breeding higher-yielding rice varieties above what is currently achievable.

Recent advances in selective mono-/dichalcogenation and exclusive dichalcogenation of C(sp2)-H and C(sp3)-H bonds.

Organochalcogen compounds are prevalent in numerous natural products, pharmaceuticals, agrochemicals, polymers, biological molecules and synthetic intermediates. Direct chalcogenation of C-H bonds has evolved as a step- and atom-economical method for the synthesis of chalcogen-bearing compounds. Nevertheless, direct C-H chalcogenation severely lags behind C-C, C-N and C-O bond formations. Moreover, compared with the C-H monochalcogenation, reports of selective mono-/dichalcogenation and exclusive dichalcogenation of C-H bonds are relatively scarce. The past decade has witnessed significant advancements in selective mono-/dichalcogenation and exclusive dichalcogenation of various C(sp2)-H and C(sp3)-H bonds via transition-metal-catalyzed/mediated, photocatalytic, electrochemical or metal-free approaches. In light of the significance of both mono- and dichalcogen-containing compounds in various fields of chemical science and the critical issue of chemoselectivity in organic synthesis, the present review systematically summarizes the advances in these research fields, with a special focus on elucidating scopes and mechanistic aspects. Moreover, the synthetic limitations, applications of some of these processes, the current challenges and our own perspectives on these highly active research fields are also discussed. Based on the substrate types and C-H bonds being chalcogenated, the present review is organized into four sections: (1) transition-metal-catalyzed/mediated chelation-assisted selective C-H mono-/dichalcogenation or exclusive dichalcogenation of (hetero)arenes; (2) directing group-free selective C-H mono-/dichalcogenation or exclusive dichalcogenation of electron-rich (hetero)arenes; (3) C(sp3)-H dichalcogenation; (4) dichalcogenation of both C(sp2)-H and C(sp3)-H bonds. We believe the present review will serve as an invaluable resource for future innovations and drug discovery.

IGF-1's protective effect on OSAS rats' learning and memory.

PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) frequently experience cognitive dysfunction, which may be connected to chronic intermittent hypoxia (CIH). Insulin-like growth factor-1 (IGF-1) is thought to be closely associated with cognitive function, but its role in cognitive impairment caused by OSAS is unclear. The purpose of this study was to investigate the potential protective effect of IGF-1 on cognitive impairment in OSAS rats. METHODS: Healthy male SD rats (n = 40) were randomly assigned into four groups: control group, CIH group, NS + CIH group, and IGF-1 + CIH group. All experimental rats except for those in the control group were exposed to intermittent hypoxic (IH) environments for 8 h per day over 28 days. Prior to daily exposure to IH, rats in the IGF-1 + CIH group received subcutaneous injections of IGF-1. The Morris water maze test was conducted on all experimental rats. Brain tissue testing methods included Enzyme-Linked Immunosorbent Assay, Hematoxylin and eosin staining, Immunohistochemistry, and Western blotting. RESULTS: The rat model of OSAS was successfully established following exposure to CIH and exhibited significant cognitive impairment. However, daily subcutaneous injections of IGF-1 partially restored the impaired cognitive function in OSAS rats. Compared with the control group, there was a significant decrease in the expression levels of IGF-1, p-IGF-IR, and SYP in the CIH group; however, these expression levels increased significantly in the IGF-I + CIH group. CONCLUSION: In OSAS rats, IGF-1 enhances learning memory; this effect may be linked to increased p-IGF-1R and SYP protein production in the hippocampus.

EGR1 mediates METTL3/m6A/CHI3L1 to promote osteoclastogenesis in osteoporosis.

OBJECTIVE: To investigate EGR1-mediated METTL3/m6A/CHI3L1 axis in osteoporosis. METHODS: Ovariectomy (OVX) was performed on mice to induce osteoporosis, followed by µ-CT scanning of femurs, histological staining, immunohistochemistry analysis of MMP9 and NFATc1, and ELISA of serum BGP, ALP, Ca, and CTXI. The isolated mouse bone marrow mononuclear macrophages (BMMs) were differentiated into osteoclasts under cytokine stimulation. TRAP staining was performed to quantify osteoclasts. The levels of Nfatc1, c-Fos, Acp5, and Ctsk in osteoclasts, m6A level, and the relationships among EGR1, METTL3, and CHI3L1 were analyzed. RESULTS: The EGR1/METTL3/CHI3L1 levels and m6A level were upregulated in osteoporotic mice and the derived BMMs. EGR1 was a transcription factor of METTL3. METTL3 promoted the post-transcriptional regulation of CHI3L1 by increasing m6A methylation. EGR1 downregulation reduced BMMs-differentiated osteoclasts and alleviated OVX-induced osteoporosis by regulating the METTL3/m6A/CHI3L1 axis. CONCLUSION: EGR1 promotes METTL3 transcription and increases m6A-modified CHI3L1 level, thereby stimulating osteoclast differentiation and osteoporosis development.

Merging C-H Bond Activation, Alkyne Insertion, and Rearrangements by Rh(III)-Catalysis: Oxindole Synthesis from Nitroarenes and Alkynes.

We report a Rh(III)-catalyzed ortho-C-H bond functionalization of nitroarenes with 1,2-diarylalkynes and carboxylic anhydrides. The reaction unpredictably affords 3,3-disubstituted oxindoles with the formal reduction of the nitro group under redox-neutral conditions. Besides good functional group tolerance, this transformation allows the preparation of oxindoles with a quaternary carbon stereocenter using nonsymmetrical 1,2-diarylalkynes. This protocol is facilitated by the use of a functionalized cyclopentadienyl (CpTMP*)Rh(III) [CpTMP* = 1-(3,4,5-trimethoxyphenyl)-2,3,4,5-tetramethylcyclopentadienyl] catalyst we developed, which combines an electron-rich character with an elliptical shape. Mechanistic investigations, including the isolation of three rhodacyle intermediates and extensive density functional theory calculations, indicate that the reaction proceeds through nitrosoarene intermediates via a cascade of C-H bond activation─O-atom transfer─[1,2]-aryl shift─deoxygenation─N-acylation.

A spatiotemporally regulated transcriptional complex underlies heteroblastic development of leaf hairs in Arabidopsis thaliana.

Heteroblasty refers to a phenomenon that a plant produces morphologically or functionally different lateral organs in an age-dependent manner. In the model plant Arabidopsis thaliana, the production of trichomes (epidermal leaf hairs) on the abaxial (lower) side of leaves is a heteroblastic mark for the juvenile-to-adult transition. Here, we show that the heteroblastic development of abaxial trichomes is regulated by a spatiotemporally regulated complex comprising the leaf abaxial fate determinant (KAN1) and the developmental timer (miR172-targeted AP2-like proteins). We provide evidence that a short-distance chromatin loop brings the downstream enhancer element into close association with the promoter elements of GL1, which encodes a MYB transcription factor essential for trichome initiation. During juvenile phase, the KAN1-AP2 repressive complex binds to the downstream sequence of GL1 and represses its expression through chromatin looping. As plants age, the gradual reduction in AP2-like protein levels leads to decreased amount of the KAN1-AP2 complex, thereby licensing GL1 expression and the abaxial trichome initiation. Our results thus reveal a novel molecular mechanism by which a heteroblastic trait is governed by integrating age and leaf polarity cue in plants.

A scheme for rapid evaluation of the intermolecular three-body polarization effect in water clusters.

The ability to accurately and rapidly evaluate the intermolecular many-body polarization effect of the water system is very important for computer simulations of biomolecule in aqueous. In this paper, a scheme is proposed based on the polarizable dipole-dipole interaction model and used to rapidly estimate the intermolecular many-body polarization effect in water clusters. We use a bond-dipole-based polarization function to evaluate the polarization energy. We regard two OH bonds of a water molecule as two bond-dipoles and set the permanent OH bond-dipole moment of a water molecule to be 1.51 Debye. We estimate the induced OH bond-dipole moment via a simple formula in which only one correction factor is needed. This scheme is then applied to tens of water clusters to calculate the three- and four-body interaction energies. The three-body interaction energies of 93 water clusters produced by our scheme are compared with those produced by the counterpoise-corrected CCSD(T)/aug-cc-pVDZ, MP2/aug-cc-pVDZ, M06-2X/jul-cc-pVTZ methods, by the AMOEBApro13, iAMOEBA, AMOEBA+, AMOEBA+(CF) methods, and by the MB-pol method. The four-body interaction energies of 47 water clusters yielded by our scheme are compared with those yielded by the counterpoise-corrected MP2/aug-cc-pVDZ and M06-2X/ jul-cc-pVTZ methods, by the AMOEBApro13, AMOEBA+, AMOEBA+(CF) methods, and by the MB-pol method. The comparison results show that the scheme proposed in this paper can reproduce the counterpoise-corrected CCSD(T)/aug-cc-pVDZ three-body interaction energies and reproduce the counterpoise-corrected MP2/aug-cc-pVDZ four-body interaction energies both accurately and efficiently. We anticipate the scheme proposed here can be useful for computer simulations of liquid water and aqueous solutions.

A retrotransposon insertion in MUTL-HOMOLOG 1 affects wild rice seed set and cultivated rice crossover rate.

Wild rice (Oryza rufipogon) has a lower panicle seed setting rate (PSSR) and gamete fertility than domesticated rice (Oryza sativa), but the genetic mechanisms of this phenomenon remain unknown. Here, we cloned a null allele of OsMLH1, an ortholog of MutL-homolog 1 to yeast and mammals, from wild rice O. rufipogon W1943 and revealed a 5.4-kb retrotransposon insertion in OsMLH1 is responsible for the low PSSR in wild rice. In contrast to the wild-type, a near isogenic line NIL-mlh1 exhibits defective crossover (CO) formation during meiosis, resulting in reduced pollen viability, partial embryo lethality, and low PSSR. Except for the mutant of mismatch repair gene postmeiotic segregation 1 (Ospms1), all other MutL mutants from O. sativa indica subspecies displayed male and female semi-sterility similar to NIL-mlh1, but less severe than those from O. sativa japonica subspecies. MLH1 and MLH3 did not contribute in an additive fashion to fertility. Two types of MutL heterodimers, MLH1-PMS1 and MLH1-MLH3, were identified in rice, but only the latter functions in promoting meiotic CO formation. Compared to japonica varieties, indica cultivars had greater numbers of CO events per meiosis. Our results suggest that low fertility in wild rice may be caused by different gene defects, and indica and japonica subspecies have substantially different CO rates responsible for the discrepancy between the fertility of mlh1 and mlh3 mutants.

Second-order statistics of a Hermite-Gaussian correlated Schell-model beam carrying twisted phase propagation in turbulent atmosphere.

We investigate the second-order statistics of a twisted Hermite-Gaussian correlated Schell-model (THGCSM) beam propagation in turbulent atmosphere, including the spectral density, degree of coherence (DOC), root mean square (r.m.s.) beam wander and orbital angular momentum (OAM) flux density. Our results reveal that the atmospheric turbulence and the twist phase play a role in preventing the beam splitting during beam propagation. However, the two factors have opposite effects on the evolution of the DOC. The twist phase preserves the DOC profile invariant on propagation, whereas the turbulence degenerates the DOC. In addition, the influences of the beam parameters and the turbulence on the beam wander are also studied through numerical examples, which show that the beam wander can be reduced by modulating the initial parameters of the beam. Further, the behavior of the z-component OAM flux density in free space and in atmosphere is thoroughly examined. We show that the direction of the OAM flux density without the twist phase will be suddenly inversed at each point across the beam section in the turbulence. This inversion only depends on the initial beam width and the turbulence strength, and in turn, it offers an effective protocol to determine the turbulence strength by measuring the propagation distance where the direction of OAM flux density is inversed.

Suberoylanilide Hydroxamic Acid Ameliorates Pain Sensitization in Central Neuropathic Pain After Spinal Cord Injury via the HDAC5/NEDD4/SCN9A Axis.

Pain sensitization in spinal cord injury (SCI)-induced central neuropathic pain has been a research target. Additionally, suberoylanilide hydroxamic acid (SAHA) has been reported to protect against pain hypersensitivity in central neuropathic pain. Hence, this research probed the impact of SAHA on pain sensitization in central neuropathic pain after SCI via the HDAC5/NEDD4/SCN9A axis. After SAHA treatment, SCI modeling, and gain- and loss-of-function assays, behavioral analysis was performed in mice to evaluate pain hypersensitivity and anxiety/depression-like behaviors. The enrichment of H3K27Ac in the NEDD4 promoter and the ubiquitination of SCN9A were measured with ChIP and Co-IP assays, respectively. The treatment of SAHA regained paw withdrawal threshold and paw withdrawal latency values, entry time and numbers in the center area, and entry proportion in the open arm for SCI mice, accompanied by decreases in immobility time, eating latency, thermal hyperalgesia, and mechanical ectopic pain. However, SAHA treatment did not affect the motor function of mice. SAHA treatment lowered HDAC5 expression and SCN9A protein expression in SCI mice, as well as enhanced SCN9A ubiquitination and NEDD4 expression. HDAC5 knockdown greatly increased H3K27Ac enrichment in the NEDD4 promoter. NEDD4 upregulation or HDAC5 knockdown elevated SCN9A ubiquitination but diminished SCN9A protein expression in dorsal root ganglions of SCI mice. NEDD4 silencing mitigated the improving effects of SAHA treatment on the pain hypersensitivity and anxiety/depression-like behaviors of SCI mice. SAHA suppressed HDAC5 to augment NEDD4 expression and SCN9A degradation, thereby ameliorating the pain hypersensitivity and anxiety/depression-like behaviors of SCI mice.

The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation.

PURPOSE: To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). METHODS: Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iß (IL-1ß) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1ß. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. RESULTS: Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1ß and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1ß compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). CONCLUSION: Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.

From bonds to interactions: comprehensive molecular characterization via polarizable bond-dipole approach.

Accurately characterizing molecular interactions stands as a pivotal requirement for ensuring the reliability of molecular dynamics simulations. In line with our bond-dipole-based interaction model proposed by Gao et al. [X.-C. Gao, Q. Hao and C.-S. Wang, J. Chem. Theory Comput., 2017, 13, 2730-2741.], we have implemented an efficient and concise approach to compute electrostatic potential. This methodology capitalizes on the polarizable nature of chemical bond dipoles, resulting in a model of remarkable simplicity. In this study, we have revised the polarizable bond-dipole-based force field (PBFF) through the meticulous curation of quantum chemical data sets. These data sets encompass a comprehensive collection of 40 000 conformations, including those of water, methylamine, methanol, and N-methylacetamide. Additionally, we incorporate 520 hydrogen-bonded dimers into our data sets. In pursuit of enhanced accuracy in molecular dynamics simulations and a more faithful representation of potential energy landscapes, we undertook the re-optimization of the nonbonded parameters within the PBFF framework. Concurrently, we intricately fine-tuned the bonded parameters. The results of our comprehensive evaluation denote that this newly optimized force field method adeptly and efficiently computes structural characteristics, harmonic frequencies, and interaction energies. Overall, this study provides further validation for the applicability of PBFF in molecular dynamics simulations.

First Report of Cercospora citrullina Causing Spot Disease on Watermelon in China.

Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai], Cucurbitaceae family, is an important vegetable crop. It is believed to be native to Africa and is cultivated in the temperate regions of Africa, central Asia, Americas and the Mediterranean (Chomicki & Renner 2015). China is the largest producer and consumer of watermelon, with an annual production of about 60.25 million tons in 2020 (https://www.fao.org/faostat/en/#home). In May 2022, a new fungal disease was observed on the leaves, vines and fruits of watermelon (cv. Heimeiren, 8424, Qilin) with an incidence of up to 75% in greenhouses, in Gudi Industrial Park, Hanting district, Weifang City, Shandong Province, China. The symptomatic leaves, vines and fruits showed small circular black spots. The disease caused the leaves and vines to desiccate rapidly, and severely affected the fruit quality. Symptomatic leaves, vines and fruits were randomly collected, and isolations were performed from infected tissues. The edges of necrotic lesions were cut into small pieces (about 5 mm), surface sterilized with 2% NaClO for 2 min, followed by 75% ethanol for 30 s, rinsed three times in sterile distilled water and placed in Petri dishes on potato dextrose agar (PDA). The same fungus was isolated from all tissue pieces and formed colonies white fluffy on the surface, and dark gray on the reverse side after 7 days incubation at 25oC. Colonies were subcultured on PDA and Corn Meal Agar (CMA), respectively, and grew slowly (the diameter was approximately 2 cm in 10 days) on PDA showing a white edge, but they grew more rapidly on CMA (approximately 3.5 cm in diameter after 10 days incubation) showing an orange halo. Hyphae were branched, brown and smooth. Conidiophores were fasciculate, brown, straight, unbranched and measured 20.03 to 304.08 × 3.41 to 6.41 µm. Conidia were needle-shaped to clavate, colorless, erect or curved and measured 22.53 to 243.97 × 3.16 to 7.02 µm. According to these morphological characteristics, the fungus was tentatively identified as Cercospora spp. (Chupp 1954). To determine the species of the fungus, three representative isolates, UNL090101, UNL090102 and UNL090103 obtained from symptomatic leaves, vines and fruits, respectively, were characterized. The genomic DNA was extracted to amplify the nuclear ribosomal internal transcribed spacer (ITS) region, translation elongation factor 1-α (TEF-1), histone H3 (HIS), and actin (ACT) genes, using the following primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone & Kohn 1999), CYLH3F/CYLH3R (Crous et al. 2004), ACT-512F/ACT-783R (Carbone & Kohn 1999), respectively. The ITS, EF-1, HIS, and ACT gene sequences were blasted and deposited in GenBank (accession numbers ON849061/OQ102622/OQ102623, ON890306/OQ108278/OQ108281, ON890307/OQ108279/OQ108282 and ON890308/OQ108280/OQ108283, respectively). A phylogenetic tree based on concatenated sequences of ITS-CAT-TEF-H3 from the genus Cerospora was constructed using the maximum likelihood method. Isolates from watermelon and C. citrullina formed a monophyletic group with 100% bootstrap support, which was in accordance with BLAST results. Therefore, the fungus associated to watermelon spot disease was identified as C. citrullina. To fulfill the Koch's postulates, each of the three isolates was artificially inoculated onto watermelon (cv. Qilin) detached expanded leaves, vines and fruits. Three wounds were made with sterilized entomological needles on each leaf, vine and fruit, and each wound was inoculated with 6 mm CMA medium with the fungus, and without fungus as control. All the experiments were conducted for three times. All the inoculated and control leaves were placed in an incubator and incubated at 28oC and 85% relative humidity, with a 12 h photoperiod. Three days after inoculation, the inoculated leaves showed similar symptoms to those observed on naturally infected plants, while the control leaves remained asymptomatic. C. citrullina was re-isolated from symptomatic artificially inoculated leaves and identified by microscopy and re-sequencing, thus fulfilling Koch's postulates. C. citrullina has been reported on several Cucurbitaceae plants worldwide, eg. on watermelon in South Carolina (Rennberger et al. 2019) and on Burcucumber (Sicyos angulatus L.) in Korea (Hong et al. 2014), but, to our knowledge, this is the first report of C. citrullina causing spot disease on watermelon in China.

Observation of the Orbital Rashba-Edelstein Magnetoresistance.

We report the observation of magnetoresistance (MR) that could originate from the orbital angular momentum (OAM) transport in a permalloy (Py)/oxidized Cu (Cu^{*}) heterostructure: the orbital Rashba-Edelstein magnetoresistance. The angular dependence of the MR depends on the relative angle between the induced OAM and the magnetization in a similar fashion as the spin Hall magnetoresistance. Despite the absence of elements with large spin-orbit coupling, we find a sizable MR ratio, which is in contrast to the conventional spin Hall magnetoresistance which requires heavy elements. Through Py thickness-dependence studies, we conclude another mechanism beyond the conventional spin-based scenario is responsible for the MR observed in Py/Cu^{*} structures-originated in a sizable transport of OAM. Our findings not only suggest the current-induced torques without using any heavy elements via the OAM channel but also provide an important clue towards the microscopic understanding of the role that OAM transport can play for magnetization dynamics.

NBR2/miR-561-5p/DLC1 axis inhibited the development of multiple myeloma by activating the AMPK/mTOR pathway to repress glycolysis.

Long non-coding RNA NBR2 exerts a tumor-suppressive effect in a variety of cancers, but its role in multiple myeloma (MM) is unclear. This article will elucidate the role of NBR2 in MM. The expressions of NBR2, miR-561-5p, and deleted in liver cancer 1 (DLC1) in MM cell lines were determined by quantitative real time polymerase chain reaction (qRT-PCR). The regulatory relationship of the NBR2/miR-561-5p/DLC1 axis was predicted by bioinformatics and confirmed via a dual-luciferase reporter assay. The effect of NBR2 on the biological behavior of MM cells was verified by loss- and gain-of-function experiments (cell counting kit-8, colony formation, flow cytometry, extracellular acidification rate, and lactate production measurement). The effects of the NBR2/miR-561-5p axis on the biological behavior of MM cells, the activation of the AMPK/mTOR signaling pathway (western blot), and DLC1 expression (western blot) were verified by rescue experiments. The upregulation of NBR2 in MM cell lines induced a decrease in the viability, proliferation capacity, glycolysis, and lactic acid production, and an increase in apoptosis of MM cells. NBR2 regulated the biological behavior of MM cells and the activation of the AMPK/mTOR signaling pathway by targeting miR-561-5p. DLC1 was the target gene of miR-561-5p and the protein expression of DLC1 was regulated by the NBR2/miR-561-5p axis. Collectively, NBR2/miR-561-5p/DLC1 axis inhibits the development of MM by activating the AMPK/mTOR pathway to repress glycolysis.

Chromosomal-level genome assembly of the semi-dwarf rice Taichung Native 1, an initiator of Green Revolution.

Here we report the 409.5 Mb chromosome-level assembly of the first bred semi-dwarf rice, the Taichung Native 1 (TN1), which served as the template for the development of the Green Revolution (GR) cultivar IR8 "miracle rice". We sequenced the TN1 genome utilizing multiple platforms and produced PacBio long reads, Illumina paired-end reads, Illumina mate-pair reads and 10x Genomics linked reads. We used a hybrid approach to assemble the 226× coverage of sequences by a combination of de novo and reference-guided approaches. The assembled TN1 genome has an N50 scaffold size of 33.1 Mb with the longest measuring 45.5 Mb. We annotated 37,526 genes, in which 24,102 (64.23%) were assigned Blast2GO annotations. The genome has 4672 or 95.4% complete BUSCOs and a repeat content of 51.52%. We developed our own method of creating a GR pangenome using the orthologous relationships of the proteins of TN1, IR8, MH63 and IR64, identifying 16,999 core orthologue groups of Green Revolution. From the pangenome, we identified a set of shared and unique gene ontology terms for the accessory clusters, characterizing TN1, IR8, MH63 and IR64. This TN1 genome assembly and GR pangenome will be a resource for new genomic discoveries about Green Revolution, and for improving the disease and insect resistances and the yield of rice.

QTLs and candidate genes analyses for fruit size under domestication and differentiation in melon (Cucumis melo L.) based on high resolution maps.

BACKGROUND: Melon is a very important horticultural crop produced worldwide with high phenotypic diversity. Fruit size is among the most important domestication and differentiation traits in melon. The molecular mechanisms of fruit size in melon are largely unknown. RESULTS: Two high-density genetic maps were constructed by whole-genome resequencing with two F2 segregating populations (WAP and MAP) derived from two crosses (cultivated agrestis × wild agrestis and cultivated melo × cultivated agrestis). We obtained 1,871,671 and 1,976,589 high quality SNPs that show differences between parents in WAP and MAP. A total of 5138 and 5839 recombination events generated 954 bins in WAP and 1027 bins in MAP with the average size of 321.3 Kb and 301.4 Kb respectively. All bins were mapped onto 12 linkage groups in WAP and MAP. The total lengths of two linkage maps were 904.4 cM (WAP) and 874.5 cM (MAP), covering 86.6% and 87.4% of the melon genome. Two loci for fruit size were identified on chromosome 11 in WAP and chromosome 5 in MAP, respectively. An auxin response factor and a YABBY transcription factor were inferred to be the candidate genes for both loci. CONCLUSION: The high-resolution genetic maps and QTLs analyses for fruit size described here will provide a better understanding the genetic basis of domestication and differentiation, and provide a valuable tool for map-based cloning and molecular marker assisted breeding.

Understanding the Effect of Conformational Rigidity on Rheological Behavior and Formation of Polysaccharide-Based Hybrid Hydrogels.

The importance of conformational rigidity on macroscopic rheological properties was revealed using two model polysaccharides, namely, xanthan gum and hyaluronic acid. Xanthan gum has a rigid tertiary conformation due to its ordered double-helical structure, and the interactions between the tertiary structures result in the formation of a network/quaternary structure. In comparison, hyaluronic acid possesses a relatively flexible tertiary conformation due to its secondary random coil structure. Xanthan gum exhibits a much stronger shear thinning and more solidlike behavior compared to hyaluronic acid, owing to its network/quaternary structure. The rigid tertiary structure and the presence of a network/quaternary structure also endow xanthan gum with better resistance against environmental changes (e.g., salt and/or urea addition, temperature change) compared to hyaluronic acid. The network/quaternary structure allows xanthan gum to form gels with chitosan via electrostatic interactions when using the vapor-induced gelation technique, which is not possible for hyaluronic acid due to its flexible tertiary conformation under similar conditions.

Robust Cobalt Catalyst for Nitrile/Alkyne [2+2+2] Cycloaddition: Synthesis of Polyarylpyridines and Their Mechanochemical Cyclodehydrogenation to Nitrogen-Containing Polyaromatics*.

The transition-metal-catalyzed [2+2+2] cycloaddition of nitriles and alkynes is an established synthetic approach to pyridines; however, these cycloadditions often rely on the use of tethered diynes or cyanoalkynes as one of the reactants. Thus, examples of efficient, fully intermolecular catalytic [2+2+2] pyridine synthesis, especially those employing unactivated nitriles and internal alkynes leading to pentasubstituted pyridines, remain scarce. Herein, we report on simple and inexpensive catalytic systems based on cobalt(II) iodide, 1,3-bis(diphenylphosphino)propane, and Zn that promote [2+2+2] cycloaddition of various nitriles and diarylacetylenes for the synthesis of a broad range of polyarylated pyridines. DFT studies support a reaction pathway involving oxidative coupling of two alkynes, insertion of the nitrile into a cobaltacyclopentadiene, and C-N reductive elimination. The resulting tetra- and pentaarylpyridines serve as precursors to hitherto unprecedented nitrogen-containing polycyclic aromatic hydrocarbons via mechanochemically assisted multifold reductive cyclodehydrogenation.