Synergistic therapeutic effect of ginsenoside Rg3 modified minoxidil transfersomes (MXD-Rg3@TFs) on androgenic alopecia in C57BL/6 mice.

Inflammation in hair follicles will reduce the effectiveness of minoxidil (MXD) in the treatment of androgen alopecia (AGA) caused by elevated androgen levels. To target multiple physiological and pathological processes in AGA, a novel natural bioactive compound modified transfersomes (MXD-Rg3@TFs) was prepared to replace cholesterol that may disrupt hair growth, with ginsenosides Rg3 (Rg3) that have anti-inflammatory effects on AGA. The effects of MXD, Rg3 and their combination on AGA were evaluated using dihydrotestosterone (DHT) induced human dermal papilla cells (DPCs), and the results showed that the combination of MXD and Rg3 can significantly promote the proliferation, reduce the level of intracellular ROS and inflammatory factors, and inhibit the aging of DHT induced DPCs. Compared with cholesterol membrane transfersomes (MXD-Ch@TFs), MXD-Rg3@TFs has similar deformability, smaller particle size and better stability. MXD-Rg3@TFs has also significant advantages in shortening telogen phase and prolonging the growth period of hair follicles in C57BL/6 mice than MXD-Ch@TFs and commercial MXD tincture. The prominent ability of MXD-Rg3@TFs to inhibit the conversion of testosterone to DHT and reduce the level of inflammatory factors suggested that Rg3 and MXD in MXD-Rg3@TFs have synergistic effect on AGA therapy. MXD-Ch@TFs with no irritation to C57BL/6 mice skin is expected to reduce the dose of MXD and shorten the treatment time, which would undoubtedly provide a promising therapeutic option for treatment of AGA.

[Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia].

OBJECTIVE: To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). METHODS: From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. RESULTS: The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). CONCLUSION: The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

DSSS Signal Detection Based on CNN.

With the wide application of direct sequence spread spectrum (DSSS) signals, the comprehensive performance of DSSS communication systems has been continuously improved, making the electronic reconnaissance link in communication countermeasures more difficult. Electronic reconnaissance technology, as the fundamental means of modern electronic warfare, mainly includes signal detection, recognition, and parameter estimation. At present, research on DSSS detection algorithms is mostly based on the correlation characteristics of DSSS signals, and autocorrelation algorithm is the most mature and widely used method in practical engineering. With the continuous development of deep learning, deep-learning-based methods have gradually been introduced to replace traditional algorithms in the field of signal processing. This paper proposes a spread spectrum signal detection method based on convolutional neural network (CNN). Through experimental analysis, the detection performance of the CNN model proposed in this paper on DSSS signals in various situations has been compared and analyzed with traditional autocorrelation detection methods for different signal-to-noise ratios. The experiments verified the estimation performance of the model in this paper under different signal-to-noise ratios, different spreading code lengths, different spreading code types, and different modulation methods and compared it with the autocorrelation detection algorithm. It was found that the detection performance of the model in this paper was higher than that of the autocorrelation detection method, and the overall performance was improved by 4 dB.

Period Estimation of Spread Spectrum Codes Based on ResNet.

In order to more effectively monitor and interfere with enemy signals, it is particularly important to accurately and efficiently identify the intercepted signals and estimate their parameters in the increasingly complex electromagnetic environment. Therefore, in non-cooperative situations, it is of great practical significance to study how to accurately detect direct sequence spread spectrum (DSSS) signals in real time and estimate their parameters. The traditional time-delay correlation algorithm encounters the challenges such as peak energy leakage and false peak interference. As an alternative, this paper introduces a Pseudo-Noise (PN) code period estimation method utilizing a one-dimensional (1D) convolutional neural network based on the residual network (CNN-ResNet). This method transforms the problem of spread spectrum code period estimation into a multi-classification problem of spread spectrum code length estimation. Firstly, the In-phase/Quadrature(I/Q) two-way of the received DSSS signals is directly input into the CNN-ResNet model, which will automatically learn the characteristics of the DSSS signal with different PN code lengths and then estimate the PN code length. Simulation experiments are conducted using a data set with DSSS signals ranging from -20 to 10 dB in terms of signal-to-noise ratios (SNRs). Upon training and verifying the model using BPSK modulation, it is then put to the test with QPSK-modulated signals, and the estimation performance was analyzed through metrics such as loss function, accuracy rate, recall rate, and confusion matrix. The results demonstrate that the 1D CNN-ResNet proposed in this paper is capable of effectively estimating the PN code period of the non-cooperative DSSS signal, exhibiting robust generalization abilities.

[Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis. METHODS: A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ï¼»66 cases of them were screened by propensity score matching (PSM), as control groupï¼½. The early efficacy and survival between the two groups were compared. RESULTS: The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively. CONCLUSION: Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Climate suitability division of solar greenhouse in Inner Mongolia Autonomous Region, China.

To resolve the issue of scientific planning and rational layout of different vegetable greenhouses in Inner Mongolia Autonomous Region, we selected the days of low temperature in winter, sunshine hours, overcast days, extreme minimum temperature, days of monsoon disaster, days of snow cover in production season of greenhouse as the climate zoning indicators, based on ground-based observation data from 119 meteorological stations (1991 to 2020) and the growing demand of leafy and fruity vegetables in greenhouse, combined with the analysis of key meteorological factors in production season and the study of meteorological disaster indicators such as low temperature and cold damage, wind disaster, snow disaster. We analyzed the indices, classification and division of comprehensive climate suitability zoning of leafy and fruity vegetables at various slopes (35°, 40°) of solar greenhouse by the weighted sum method. The results showed that the climatic suitability zoning grades of leafy and fruity vegetables at 35° and 40° slope of greenhouse was highly consistent, and that the greenhouse climate suitability of leafy vegetables was higher than that of fruity vegetables in the same region. As the slope increased, wind disaster index decreased and snow disaster index increased. Climate suitability was different in areas affected by wind and snow disasters. The northeast of the study area was mainly affected by snow disasters, and the climate suitability of 40° slope was higher than 35°. The southeast of the study area was mainly affected by wind disasters, and the climate suitability of 35° slope was higher than 40°. Alxa League, Hetao Irrigation District, Tumochuan Plain, most parts of Ordos, southeast of Yanshan foothills and the south of West Liaohe Plain were the most suitable area for the solar greenhouse, because they had the suitable solar and hot resources and the low risks of wind and snow damage, which were also the key development areas of current and future facility agriculture. Due to the deficiency of solar and hot resources, high energy consumption in greenhouse production and frequent snow storms, the area around Khingan range in the northeast of Inner Mongolia was unsuitable for greenhouse.

LncRNA NEAT1 antagonizes the inhibition of melanoma proliferation, migration, invasion and EMT by Polyphyllin B.

Polyphyllin B (PPB) is a compound with anti-tumor effects. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long-stranded noncoding RNA that induces epithelial-mesenchymal transition (EMT) of tumor cells and promotes tumor growth and metastasis. However, the role and mechanism of PPB on melanoma and the correlation between them remain unclear. In this study we screened NEAT1 by using LncRNA transcriptomic sequencing, and then transfected B16F10 cells using OVER-NEAT1 lentivirus. Next, we found that PPB had significant proliferation inhibition of melanoma and B16F10 cells through MTT assay and establishment of mouse subcutaneous transplantation tumor model; in addition, through wound healing assay, transwell assay and establishment of mouse melanoma lung metastasis model, we found that PPB significantly inhibited the invasion and migration of B16F10 cells in vitro, and inhibited the metastasis of melanoma to lung, bone and liver in vivo. Finally, changes in the expression levels of EMT-related proteins were assessed by western blot (WB) and immunohistochemistry, and PPB significantly downregulated the expression levels of MMP-9, N-cadherin, etc., and upregulated E-cadherin. While overexpressed NEAT1 showed the ability to promote melanoma proliferation, migration and invasion, in addition to partially reversed the inhibition of proliferation, migration and invasion of melanoma by PPB mentioned above.

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease.

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.

One-Step Route to Fe2O3 and FeSe2 Nanoparticles Loaded on Carbon-Sheet for Lithium Storage.

Iron-based anode materials, such as Fe2O3 and FeSe2 have attracted widespread attention for lithium-ion batteries due to their high capacities. However, the capacity decays seriously because of poor conductivity and severe volume expansion. Designing nanostructures combined with carbon are effective means to improve cycling stability. In this work, ultra-small Fe2O3 nanoparticles loaded on a carbon framework were synthesized through a one-step thermal decomposition of the commercial C15H21FeO6 [Iron (III) acetylacetonate], which could be served as the source of Fe, O, and C. As an anode material, the Fe2O3@C anode delivers a specific capacity of 747.8 mAh g-1 after 200 cycles at 200 mA g-1 and 577.8 mAh g-1 after 365 cycles at 500 mA g-1. When selenium powder was introduced into the reaction system, the FeSe2 nano-rods encapsulated in the carbon shell were obtained, which also displayed a relatively good performance in lithium storage capacity (852 mAh g-1 after 150 cycles under the current density of 100 mA·g-1). This study may provide an alternative way to prepare other carbon-composited metal compounds, such as FeNx@C, FePx@C, and FeSx@C, and found their applications in the field of electrochemistry.

Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report.

BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid ß-glucosidase activity [glucocerebrosidase (GCase)]. This study aimed to identify and characterise compound heterozygous mutations in GBA1 in a patient with type 1 GD. CASE SUMMARY: Here, we report a rare adult-onset type 1 GD in a 46-year-old female patient with clinical manifestations of giant spleen, thrombocytopenia, and bone pain, diagnosed by enzymatic and genetic testing. Enzymology and whole exome sequencing revealed heterozygous missense mutations in exon 10 c.1448T>C (p.L483P) and exon 7 c.928A>G (p.S310G) of GBA1. The latter was first reported in patients with GD. Structural modelling showed that p.S310G and p.L483P were distant from the GCase active site. The p.S310G mutation in domain 1 may decrease stability between the α2 and α3 helices of GBA1. The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminal ß-sheet. The patient was treated with imiglucerase replacement therapy, and her condition was stable. CONCLUSION: The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely affects GCase protein function. This is the first description of p.S310G being associated with mild type 1 GD in the context of a coinherited p.L483P mutation.

Design and synthesis of three new copper coordination polymers: efficient degradation of an organic dye at alkaline pH.

Three new coordination polymers (CPs) based on Cu(II), namely {[Cu6(H2L)4(4,4'-bpy)6(H2O)2]·16H2O}n(1), {[Cu(H3L)(1,4-bib)]·3H2O}n(2), and {[Cu2(H2L)2(1,4-bib)2][Cu(1,4-bib)(H2O)2]}n·4nH2O(3) (H5L = 6-(3',4'-dicarboxyphenoxy)-2,3,5-benzene tricarboxylic acid, 4,4'-bpy = 4,4'-bipyridine and 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene) were synthesized under hydrothermal conditions and characterized. 1 adopts a three-dimensional structure and can be described with the point symbol {4·52}2{42·54·64·83·92}{5·104·12} whereas 2 shows a layered structure. 3 can be perceived as a complex salt of two coordination polymers: the cationic component [Cu(1,4-bib)(H2O)2]n2+ (3a) represents a chain polymer and the second anionic moiety [Cu2(H2L)2(1,4-bib)2]n2- (3b) corresponds to a 2D sub-structure. In the presence of H2O2, all complexes 1-3 act as efficient photocatalysts for the degradation of the dye methylene blue (MB). The effects of properties such as initial MB concentration, catalyst dosage, pH value, and H2O2 concentration on MB degradation were also investigated and analyzed in detail. Compounds 1-3 exhibit excellent structural stability during the catalytic process and can be reused at least three times. The hydroxyl radical (OH˙) and holes (h+) were confirmed as the main active species in the degradation process.

LncRNA LINC00974 Downregulates miR-122 to Upregulate RhoA in Oral Squamous Cell Carcinoma.

Background: LncRNA LINC00974 participates in oral fibrogenesis, indicating possible involvement in other oral diseases. Results: The authors found that LINC00974 was upregulated in oral squamous cell carcinoma (OSCC) and predicted poor survival. In OSCC tissues, LINC00974 was inversely correlated with miR-122 and positively correlated with RhoA. In OSCC cells, LINC00974 overexpression resulted in upregulated, whereas overexpression of miR-122 led to downregulated RhoA. Moreover, downregulated miR-122 was observed after LINC00974 overexpression, whereas LINC00974 expression was not significantly affected by miR-122 overexpression. In invasion and migration assay, miR-122 overexpression resulted in reduced, whereas LINC00974 and RhoA overexpression resulted in increased rate of cancer cell migration and invasion. In addition, miR-122 overexpression reduced the effects of LINC00974 overexpression. Conclusion: Therefore, LINC00974 can downregulate miR-122 to upregulate RhoA in OSCC, thereby promoting cell invasion and migration.

[Exploration of the pathogenesis for a SRY-negative male with 46,XX disorder of sex development].

OBJECTIVE: To explore the pathogenesis for a SRY-negative male with 46,XX disorder of sex development (DSD). METHODS: Peripheral blood samples of the patient and his family members were subjected to chromosomal karyotyping, routine PCR, real-time fluorescence quantitative PCR, whole exome sequencing and whole genome sequencing. The data was analyzed with NextGENe software. RESULTS: Both the proband and his brother presented a 46,XX karyotype with negative SRY gene, while their father presented normal phenotype and karyotype with positive SRY gene. No pathogenic variant associated with sex development was detected by whole exome sequencing, while a 243 kb duplication was detected by whole genome sequencing in the 5' upstream region of the SOX9 gene in the proband, his brother and father. The same duplication was not found in his sister and mother. CONCLUSION: The 243 kb duplication at the 5' upstream of the SOX9 gene may predispose to the 46,XX DSD in this family. It is speculated that there exist an unknown core regulatory element in the upstream of the SOX9, and its duplication may trigger expression of SOX9 and initiate testicular differentiation in the absence of SRY gene.

BRF Negatively Regulates Thermotolerance Defect of fes1a in Arabidopsis.

FES1A is a heat shock protein 70 binding protein. Mutation of FES1A leads to a defect in thermotolerance of Arabidopsis; however, independent fes1a mutants exhibit a range in the extent of thermosensitivity. Here, we found that BRF2, a gene adjacent to FES1A and encoding a component of transcription factor IIIB, affects the thermosensitivity of fes1a mutants. Knockout of BRF2 suppressed fes1a thermosensitivity, while overexpression of BRF2 increased thermosensitivity of fes1a. BRF2 in fes1a mutants regulates the transcriptional strength of RNA Polymerase II and accumulation of heat shock proteins and eventually affects the thermotolerance of fes1a. There is a cross-talking between RNA Pol III and Pol II. The cross-talking is initiated by BRF, magnified by the mutation of FES1A, and finally has an effect on thermotolerance.

Targeted exome sequencing reveals a novel GLI3 mutation in a Chinese family with nonsyndromic polydactyly.

BACKGROUND: Polydactyly is a phenotypically and genetically highly heterogeneous limb malformation with preaxial, postaxial, and central subtypes. The aim of this study was to identify genetically pathogenic factor in a Chinese nonsyndromic polydactyly family. RESULTS: Seven family members and 100 healthy controls were recruited, and the genetically pathogenic factor of the polydactyly family was investigated by targeted exome sequencing. Targeted exome sequencing revealed a novel frameshift mutation c.2148delA (p.Gln716Hisfs*17) of GLI3 in the family. This GLI3 variant was absent in 100 healthy controls and predicted to be highly damaging to the function of the GLI3 by causing half truncation of the protein. CONCLUSION: This novel variant extended the mutational and phenotypic spectra of GLI3 and demonstrated the feasibility of targeted exome sequencing in clinical application of molecular diagnosis.

Double mutation of BRF1 and BRF2 leads to sterility in Arabidopsis thaliana.

The TFIIB-related factor (BRF) family plays vital roles in RNA polymerase (Pol) III transcription initiation. However, little is known about the role of BRF in plants. Here, we report BRF1 and BRF2 are involved in Arabidopsis reproduction. In this study, we generated BRF1 and BRF2 double mutant plants. We found that no homozygous double mutants of brf1brf2 were obtained when brf1 and brf2 were crossed, although brf1 and brf2 mutants individually developed and reproduced normally. Further experiments revealed that heterozygous brf1/ + brf2/ + produced abnormal pollen and had no seeds in some placentas of siliques. Genetic data derived from reciprocal crosses showed that BRF2 plays a dominant role in Arabidopsis reproduction. Taken together, a double mutation of BRF1 and BRF2 results in a high degree of aborted macrogametes and microgametes and complete failure in zygote generation, ultimately leading to sterility.

Increased fes1a thermotolerance is induced by BAG6 knockout.

KEY MESSAGE: (1) The fes1a bag6 double mutant shows an increased short term thermotolerance compared to fes1a. BAG6 is a suppressor of Fes1A; (2) IQ motif is essential to effective performance of BAG6. (3) Calmodulin was involved in signal transduction. (4) BAG6 is localized in the nucleus. HSP70s play an important role in the heat-induced stress tolerance of plants. However, effective HSP70 function requires the assistance of many co-chaperones. BAG6 and Fes1A are HSP70-binding proteins that are critical for Arabidopsis thaliana thermotolerance. Despite this importance, little is known about how these co-chaperones interact. In this study, we assessed the thermotolerance of a fes1a bag6 double mutant. We found that the fes1a bag6 double mutant shows an increased short-term thermotolerance compared to fes1a. However, calmodulin inhibitors diminished this enhanced thermotolerance in the fes1a bag6 double mutant. In addition, we found the IQ motif to be essential for effective BAG6 performance. Since BAG6 is localized in the nucleus, the signal transduction is likely to involve nuclear calcium signaling.

One-step growth of triangular silver nanoplates with predictable sizes on a large scale.

A one-step growth of triangular silver nanoplates on a large scale is developed by a coordination-based kinetically controlled seeded growth method, with their edge length precisely tuned from 150 nm to 1.5 µm, and surface plasmon resonance extends to full near-infrared.

Size-tailored synthesis of silver quasi-nanospheres by kinetically controlled seeded growth.

This paper describes a simple and convenient procedure to synthesize monodisperse silver (Ag) quasi-nanospheres with size tunable in a range of 19-140 nm through a one-step seeded growth strategy. Acetonitrile was employed as a coordinating ligand of a Ag(I) salt in order to achieve a low concentration of elemental Ag after reduction and thus suppression of new nucleation events. Since the addition of the seeds significantly accelerates the reduction reaction of Ag(I) by ascorbic acid, the reaction kinetics was further delicately balanced by tuning the reaction temperature, which proved to be critical in producing Ag quasi-nanospheres with uniform size and shape. This synthesis is highly scalable, so that it provides a simple yet very robust process for producing Ag quasi-nanospheres for many biological, analytical, and catalytic applications which often demand samples in large quantity and widely tunable particle sizes.