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Background: Androgenetic alopecia (AGA) causes thinning hair, but poor hair quality in balding areas and damage from UV radiation have been overlooked. Plant extracts like Platycladus orientalis flavonoids (POFs) may improve hair quality in AGA. This study examines POFs’ effectiveness in treating AGA-affected hair and repairing UV-induced damage. Methods: Hair samples were analyzed using scanning electron microscopy (SEM) to examine surface characteristics, electron paramagnetic resonance (EPR) spectroscopy to measure free radicals in the hair, and spectrophotometry to assess changes in hair properties. Results: POFs effectively removed hydroxyl radicals from keratinocytes and had antioxidant properties. They also reduced UV-induced damage to AGA hair by mitigating the production of melanin free radicals. Following POF treatment, the reduction in peroxidized lipid loss in AGA hair was notable at 59.72%, thereby effectively delaying the progression of hair color change. Moreover, protein loss decreased by 191.1 μ/g and tryptophan loss by 15.03%, ultimately enhancing hair’s tensile strength. Conclusion: compared to healthy hair, hair damaged by AGA shows more pronounced signs of damage when exposed to UV radiation. POFs help protect balding hair by reducing oxidative damage and slowing down melanin degradation.

β-Nicotinamide mononucleotide (NMN) has shown promising effects on intestinal health, and it is extensively applied as an anti-aging and Alzheimer’s disease therapeutic, due to its medicinal properties. The effects of NMN on the growth of mouse hair were observed after hair removal. The results indicated that NMN can reverse the state of hair follicle atrophy, hair thinning, and hair sparsity induced by dihydrotestosterone (DHT), compared to that of minoxidil. In addition, the action mechanisms of NMN promoting hair growth in cultured human dermal papilla cells (HDPCs) treated with DHT were investigated in detail. The incubation of HDPCs with DHT led to a decrease in cell viability and the release of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1Beta (IL-1β) and tumor necrosis factor Alpha (TNF-α). It was found that NMN can significantly lower the release of inflammatory factors induced by DHT in HDPCs. HDPCs cells are protected from oxidative stress damage by NMN, which inhibits the NF-κB p65 inflammatory signaling pathway. Moreover, the levels of androgen receptor (AR), dickkopf-1 (DKK-1), and β-catenin in the HDPCs were assessed using PCR, indicating that NMN can significantly enhance the expression of VEGF, reduced IL-6 levels and suppress the expression of AR and DKK-1, and notably increase β-catenin expression in DHT-induced HDPCs.

In the electric propulsion system, the common mode voltage (CMV) is generated at the neutral end of the stator winding. With the development of hydrogen fuel electric aircraft, high-frequency CMV can induce leakage currents, while low-frequency CMV can meet electromagnetic compatibility standards and generate electromagnetic interference. Therefore, both pose a potential threat to system stability. Traditional inverters are powerless in eliminating CMV, while two parallel inverters can eliminate CMV theoretically. Therefore, this paper adopts parallel inverters as the driving topology. For parallel inverters, optimal modulation strategies have been widely adopted to suppress CMV, but most of the strategies have not considered the suppression of low-frequency CMV. In response to the above issues, this article proposes a zero common mode voltage SPWM (ZCMV-SPWM) to eliminate high-frequency CMV and low-frequency CMV. Firstly, four non-zero voltage vectors are used to synthesize the reference voltage of each inverter. Secondly, the restriction conditions of vector synthesis are added so that the same number of \"1\" and \"0\" have the same action time. Then, the two inverters use complementary switching sequences and compare the modulated signals with two carriers, where the phase difference between the two carriers is 180°. Finally, the effectiveness of the method is verified by experiments.

Background Normal breast tissues adjacent to cancer often harbor many of the same genomic alterations as the cancer itself. However, it remains unclear whether histologically normal breast tissues carry genomic changes related to cancer development years before a cancer diagnosis. Methods Whole exome sequencing was performed to examine germline and somatic alterations in histologically normal breast tissues from women who subsequently developed breast cancer ( n  = 79, pre-diagnosis tissues) and compared these with results from breast tissues of women who did not ( n  = 81). No patient had germline mutations in cancer predisposition genes. Results The pre-diagnosis tissues had significantly more high functional impact germline variants per sample than the healthy controls ( P  = 0.034), 36.5% of affected genes were cancer hallmark genes, among these 62.4% were involved with evading growth suppressors and 5.7% with genome instability. The average number of somatic mutations were similar between the two cohorts. Mutation signature analysis revealed COSMIC signatures 3 (associated with impaired homologous recombination) as a dominant signature more frequent in pre-diagnosis tissues. At gene and variant level, nine common germline polymorphisms in two immune regulatory genes, FCGBP and TPSBP2 , and along with three somatic mutations in F13A1 , FRY and TMLHE , were significantly more frequently mutated in the pre-diagnosis samples. Conclusions Individuals who develop breast cancer have a higher germline variant burden in normal breast tissues leading to subtle deficiencies in DNA repair that in the context of other germline and somatic mutations could facilitate malignant transformation.

Evaluating the therapeutic response and survival of lung cancer patients receiving first‐line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long‐term survival of lung cancer patients receiving first‐line chemotherapy are discovered. Whole‐exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non‐small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1–C4). The long‐term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed (P < 0.001). NSCLC patients can be divided into three subtypes (S1–S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first‐line chemotherapy in lung cancer. Evaluating the therapeutic response and survival of lung cancer patients receiving first‐line chemotherapy has always been difficult. In this study whole‐exome sequencing is performed on pretherapeutic tissue samples of 186 patients (145 non‐small cell lung cancer and 41 small cell lung cancer). Several molecular signatures associated with response and survival to first‐line chemotherapy in lung cancer are identified.

In this paper, we investigate the L² boundedness of Fourier integral operator T ϕ,a with rough symbol a ∈ L ∞ S ρ m and rough phase ϕ ∈ L ∞Φ² which satises |{x : |▽ξϕ(x,ξ) - y| ≤ r}| ≤ C(r n-1 + r n ) for any ξ, y ∈ ℝ n and r > 0. We obtain that T;a is bounded on L² if m < ρ(n - 1)/2 - n/2 when 0 ≤ ρ ≤ 1/2 or m < -(n + 1)/4 when 1/2 1. When ρ = 0 or n = 1, the condition of m is sharp. Moreover, the maximal wave operator is a special class of T ϕ,a which is studied in this paper. Thus, our main theorem substantially extends and improves some known results about the maximal wave operator.

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion 1 . The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H + -ATPase that pumps protons into the apoplast 2 , yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H + -ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis . Auxin induced interactions between TMKs and H + -ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H + -ATPase and are required for auxin-induced H + -ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H + -ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling. Auxin induces transmembrane-kinase-dependent activation of H + -ATPase in the plasma membrane through phosphorylation of its penultimate threonine residue, promoting apoplastic acidification and hypocotyl cell elongation in Arabidopsis .

β-Nicotinamide mononucleotide (NMN) has shown promising effects on intestinal health, and it is extensively applied as an anti-aging and Alzheimer’s disease therapeutic, due to its medicinal properties. The effects of NMN on the growth of mouse hair were observed after hair removal. The results indicated that NMN can reverse the state of hair follicle atrophy, hair thinning, and hair sparsity induced by dihydrotestosterone (DHT), compared to that of minoxidil. In addition, the action mechanisms of NMN promoting hair growth in cultured human dermal papilla cells (HDPCs) treated with DHT were investigated in detail. The incubation of HDPCs with DHT led to a decrease in cell viability and the release of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1Beta (IL-1β) and tumor necrosis factor Alpha (TNF-α). It was found that NMN can significantly lower the release of inflammatory factors induced by DHT in HDPCs. HDPCs cells are protected from oxidative stress damage by NMN, which inhibits the NF-κB p65 inflammatory signaling pathway. Moreover, the levels of androgen receptor (AR), dickkopf-1 (DKK-1), and β-catenin in the HDPCs were assessed using PCR, indicating that NMN can significantly enhance the expression of VEGF, reduced IL-6 levels and suppress the expression of AR and DKK-1, and notably increase β-catenin expression in DHT-induced HDPCs.

Dehydroepiandrosterone (DHEA) has a promising market due to its capacity to regulate human hormone levels as well as preventing and treating various diseases. We have established a chemical esterification coupled biocatalytic-based scheme by lipase-catalyzed 4-androstene-3,17-dione (4-AD) hydrolysis to obtain the intermediate product 5-androstene-3,17-dione (5-AD), which was then asymmetrically reduced by a ketoreductase from Sphingomonas wittichii (SwiKR). Co-enzyme required for KR is regenerated by a glucose dehydrogenase (GDH) from Bacillus subtilis . This scheme is more environmentally friendly and more efficient than the current DHEA synthesis pathway. However, a significant amount of 4-AD as by-product was detected during the catalytic process. Focused on the control of by-products, we investigated the source of 4-AD and identified that it is mainly derived from the isomerization activity of SwiKR and GDH. Increasing the proportion of glucose in the catalytic system as well as optimizing the catalytic conditions drastically reduced 4-AD from 24.7 to 6.5% of total substrate amount, and the final yield of DHEA achieved 40.1 g/L. Furthermore, this is the first time that both SwiKR and GDH have been proved to be promiscuous enzymes with dehydrogenase and ketosteroid isomerase (KSI) activities, expanding knowledge of the substrate diversity of the short-chain dehydrogenase family enzymes. Key points • A strategy of coupling lipase, ketoreductase, and glucose dehydrogenase in producing DHEA from 4-AD • Both SwiKR and GDH are identified with ketosteroid isomerase activity. • Development of catalytic strategy to control by-product and achieve highly selective DHEA production Graphical abstract