Low frequency of SLC26A4 c.919-2A > G variant among patients with nonsyndromic hearing loss in Yunnan of Southwest China.

BACKGROUND: Gene variants are responsible for more than half of hearing loss, particularly in nonsyndromic hearing loss (NSHL). The most common pathogenic variant in SLC26A4 gene found in East Asian populations is c.919-2A > G followed by c.2168A > G (p.H723R). This study was to evaluate their variant frequencies in patients with NSHL from special education schools in nine different areas of Southwest China's Yunnan. METHODS: We performed molecular characterization by PCR-products directly Sanger sequencing of the SLC26A4 c.919-2AG and c.2168 A > G variants in 1167 patients with NSHL including 533 Han Chinese and 634 ethnic minorities. RESULTS: The SLC26A4 c.919-2A > G variant was discovered in 8 patients with a homozygous state (0.69%) and twenty-five heterozygous (2.14%) in 1167 patients with NSHL. The total carrier rate of the c.919-2A > G variant was found in Han Chinese patients with 4.50% and ethnic minority patients with 1.42%. A significant difference existed between the two groups (P < 0.05). The c.919-2A > G allele variant frequency was ranged from 3.93% in Kunming to zero in Lincang and Nvjiang areas of Yunnan. We further detected the SLC26A4 c.2168 A > G variant in this cohort with one homozygotes (0.09%) and seven heterozygotes (0.60%), which was detected in Baoshan, Honghe, Licang and Pu`er areas. Between Han Chinese group (0.94%) and ethnic minority group (0.47%), there was no statistical significance (P > 0.05). Three Han Chinese patients (0.26%) carried compound heterozygosity for c.919-2A > G and c.2168 A > G. CONCLUSION: These data suggest that the variants in both SLC26A4 c.919-2A > G and c.2168 A > G were relatively less frequencies in this cohort compared to the average levels in most regions of China, as well as significantly lower than that in Han-Chinese patients. These results broadened Chinese population genetic information resources and provided more detailed information for regional genetic counselling for Yunnan.

Successful therapy using high-dose furmonertinib for non-small cell lung cancer with leptomeningeal metastasis: a case report and literature review.

Background: Lung cancer is the second most common form of malignant tumor and has the highest mortality rate worldwide. Among its subtypes, lung adenocarcinoma is the most prevalent. Leptomeningeal metastasis (LM) is rare and is characterized by a dismal prognosis, with overall survival periods typically spanning 4 to 6 weeks without treatment. However, in specific cases, survival can be extended to 4 to 6 months with appropriate therapy. The recent approval of third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, aumolertinib, and furmonertinib, has introduced promising treatment options for individuals with non-small cell lung cancer (NSCLC) who develop LM after developing resistance to first- and second-generation TKIs. These third-generation TKIs exhibit an enhanced ability to penetrate the blood-brain barrier (BBB), opening up new avenues for managing this challenging condition. Case summary: We report the case of a 48-year-old Chinese man diagnosed with advanced NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. Following a pulmonary lobectomy and postoperative adjuvant therapy with gefitinib, the patient was diagnosed with LM, which was confirmed by his neurologic symptoms, cerebrospinal fluid cytologic analysis, and cranial enhancement magnetic resonance imaging. Subsequently, he received oral treatment in the form of 160 mg of furmonertinib daily. After 5 days of furmonertinib therapy, the patient recovered from lethargy, with an obvious improvement in cognitive function. Follow-up visits revealed a 6-month survival period following the LM diagnosis. Patients with NSCLC and LM typically present with severe symptoms, and the efficacy of systemic treatment, intrathecal chemotherapy, and radiotherapy remains unsatisfactory. We hope that this specific case provide valuable insights into the management of patients with EGFR mutation-associated NSCLC with LM. Conclusion: Furmonertinib, a third-generation EGFR TKI with notable BBB penetration, shows promise in LM control and the rapid alleviation of intracranial symptoms. Further investigations into appropriate dosage and toxicity management are imperative.

Half-metallic antiferromagnets induced by non-magnetic adatoms on bilayer silicene.

Transition metal-free magnetism and two-dimensional p-state half-metals have been a fascinating subject of research due to their potential applications in nanoelectronics and spintronics. By applying density functional theory calculations, we predict that bilayer silicene can be an interlayer antiferromagnetic ground state. Interestingly, the half-metallicity is realized by adsorbing non-magnetic atoms on the antiferromagnetic bilayer silicene in the absence of transition magnetic atoms, nanoribbons, ferromagnetic substrates and magnetic field. Then, on the basis of first principles calculations and theoretical analysis, we show that the realization of half-metallicity is induced by the split of antiferromagnetic degeneracy due to the localization of transfer charge from the adatom to silicene. Our findings may open a new avenue to silicene-based electronic and spintronic devices.

High mobility and enhanced photoelectric performance of two-dimensional ternary compounds NaCuX (X = S, Se, and Te).

Two-dimensional (2D) materials have attracted great interest in the field of optoelectronics in recent years due to their atomically thin structure and various electronic properties. Based on the first-principles calculations combined with the non-equilibrium Green's function (NEGF) method, we predict a set of new 2D ternary materials, sodium copper chalcogenides (NaCuX, X = S, Se, and Te). These materials not only have direct band gaps ranging from 1.2 to 1.6 eV, but also possess relatively small carrier effective masses (0.1-0.2m0) at the band edges thus high carrier mobilities (103-104 cm2 V-1 s-1), which collectively imply that they are suitable for optical-electronic applications in the visible (even in the infrared) light region. Moreover, based on the high photo responsivity (Rph), e.g., up to 0.105 A W-1 for NaCuTe, we design a series of NaCuX monolayer based high performance optoelectronic junctions. These properties indicate that NaCuX monolayers are promising candidate materials for photodetectors and photovoltaic units.

Emerging Light-Emitting Materials for Photonic Integration.

The arrival of the information explosion era is urging the development of large-bandwidth high-data-rate optical interconnection technology. Up to now, the biggest stumbling block in optical interconnections has been the lack of efficient light sources despite significant progress that has been made in germanium-on-silicon (Ge-on-Si) and III-V-on-silicon (III-V-on-Si) lasers. 2D materials and metal halide perovskites have attracted much attention in recent years, and exhibit distinctive advantages in the application of on-chip light emitters. Herein, this Progress Report reviews the recent progress made in light-emitting materials with a focus on new materials, i.e., 2D materials and metal halide perovskites. The report briefly introduces the current status of Ge-on-Si and III-V-on-Si lasers and discusses the advances of 2D and perovskite light-emitting materials for photonic integration, including their optical properties, preparation methods, as well as the light sources based on these materials. Finally, challenges and perspectives of these emerging materials on the way to the efficient light sources are discussed.

Iizukines C-E from a saline soil fungus Aspergillus iizukae.

Three new alkaloids, iizukines C-E (1-3), including two aspochalasins (1 and 2), and one brasiliamide derivative (3), along with two known aspochalasins, rosellichalasin (4) and cytochalasin Z17 (5), were isolated from the culture of Aspergillus iizukae. Compound 1 was the first aspochalasin uniquely featuring a 1,2,4-triazole functionality, and 3 showed a pair of NMR signals in CDCl3 with a ratio of about 2:1 due to the existence of conformational isomers. Their structures were determined by extensive spectroscopic analyses and single-crystal X-ray diffractions. In particular, the 1,2,4-triazole moiety in 1 was assigned on the basis of extremely valuable 1H-15N HMBC spectrum. Compound 1 exhibited cytotoxic effect towards HL-60 and A549 cell lines with IC50 values of 3.8 and 7.2 µM, respectively.

New Butenolides and Cyclopentenones from Saline Soil-Derived Fungus Aspergillus Sclerotiorum.

Three new γ-hydroxyl butenolides (1-3), a pair of new enantiomeric spiro-butenolides (4a and 4b), a pair of enantiomeric cyclopentenones (5a new and 5b new natural), and six known compounds (6-11), were isolated from Aspergillus sclerotiorum. Their structures were established by spectroscopic data and electronic circular dichroism (ECD) spectra. Two pairs of enantiomers [(+)/(-)-6c and (+)/(-)-6d] obtained from the reaction of 6 with acetyl chloride (AcCl) confirmed that 6 was a mixture of two pairs of enantiomers. In addition, the X-ray data confirmed that 7 was also a racemate. The new metabolites (1-5) were evaluated for their inhibitory activity against cancer and non-cancer cell lines. As a result, compound 1 exhibited moderate cytotoxicity to HL60 and A549 with IC50 values of 6.5 and 8.9 µM, respectively, and weak potency to HL-7702 with IC50 values of 17.6 µM. Furthermore, compounds 1-9 were screened for their antimicrobial activity using the micro-broth dilution method. MIC values of 200 µg/mL were obtained for compounds 2 and 3 towards Staphylococcus aureus and Escherichia coli, while compound 8 exhibited a MIC of 50 µ/mL towards Candida albicans.

A Review: Enhanced Anodes of Li/Na-Ion Batteries Based on Yolk-Shell Structured Nanomaterials.

Lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) have received much attention in energy storage system. In particular, among the great efforts on enhancing the performance of LIBs and SIBs, yolk-shell (YS) structured materials have emerged as a promising strategy toward improving lithium and sodium storage. YS structures possess unique interior void space, large surface area and short diffusion distance, which can solve the problems of volume expansion and aggregation of anode materials, thus enhancing the performance of LIBs and SIBs. In this review, we present a brief overview of recent advances in the novel YS structures of spheres, polyhedrons and rods with controllable morphology and compositions. Enhanced electrochemical performance of LIBs and SIBs based on these novel YS structured anode materials was discussed in detail.

Potential Antiviral Xanthones from a Coastal Saline Soil Fungus Aspergillus iizukae.

Five new (1⁻5) and two known xanthones (6 and 7), one of the latter (6) obtained for the first time as a natural product, together with three known anthraquinones, questin, penipurdin A, and questinol, were isolated from the coastal saline soil-derived Aspergillus iizukae by application of an OSMAC (one strain many compounds) approach. Their structures were determined by interpretation of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, as well as comparison of these data with those of related known compounds. Antiviral activity of xanthones 1-7 was evaluated through the cytopathic effect (CPE) inhibition assay, and compound 2 exhibited distinctly strong activity towards influenza virus (H1N1), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) with IC50 values of 44.6, 21.4, and 76.7 µM, respectively, which indicated that it was worth to further investigate it as a potential lead compound. The preliminary structure-activity relationship of the xanthones is discussed.

Raistrickiones A-E from a Highly Productive Strain of Penicillium raistrickii Generated through Thermo Change.

Three new diastereomers of polyketides (PKs), raistrickiones A−C (1⁻3), together with two new analogues, raistrickiones D and E (4 and 5), were isolated from a highly productive strain of Penicillium raistrickii, which was subjected to an experimental thermo-change strategy to tap its potential of producing new secondary metabolites. Metabolites 1 and 2 existed in a diastereomeric mixture in the crystal packing according to the X-ray data, and were laboriously separated by semi-preparative HPLC on a chiral column. The structures of 1⁻5 were determined on the basis of the detailed analyses of the spectroscopic data (UV, IR, HRESIMS, 1D, and 2D NMR), single-crystal X-ray diffractions, and comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1⁻5 represented the first case of 3,5-dihydroxy-4-methylbenzoyl derivatives of natural products. Compounds 1⁻5 exhibited moderate radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH).

Pyran Rings Containing Polyketides from Penicillium raistrickii.

Five new pyran rings containing polyketides, penicipyrans A-E (1-5), together with the known pestapyrone A (6), were isolated from the saline soil-derived Penicillium raistrickii. Their structures were determined by interpretation of NMR and HRESIMS data. The absolute configurations of compounds 4 and 5 were established by the modified Mosher's method and single-crystal X-ray diffraction analysis, respectively. These compounds possessed high structural diversity including two α-pyrones (1, 2), three isocoumarins (3, 4, 6), and one dihydropyran derivative (5). Among them, Compound 5 exhibited cytotoxicity against HL-60 and K562 cell lines with IC50 values of 4.4 and 8.5 µM, respectively.

Polaron spin filtering in an organic ferromagnetic polymer: a dynamics simulation.

We present a model study of the dynamic properties of a polaron in an organic ferromagnetic polymer by focusing on the spin correlation between the polymer backbone and the side radicals. The simulations are performed by using a tight-binding description coupled with a nonadiabatic dynamics method. We find that, in the presence of an external electric field, the polarons with both up and down spins can get trapped near the side radicals of the polymer chain unless the electric field is stronger than a critical field. However, the magnitudes of the critical electric field vary quite differently for the spin-up and spin-down polarons as a function of the number of side radicals in the polymer, leading to the exponential change of the range of the electric field within which the spin-filtering takes place. The range of the electric field increases nearly in a linear manner with the strength of the electron-lattice coupling as a result of the increase of the polaron binding energy. The impact of the strength of the spin correlation between the backbone and the side radicals on the polaron spin filtering is also discussed. These findings are expected to be useful for the design of organic-based spin filters.

Rectification inversion in oxygen substituted graphyne-graphene-based heterojunctions.

Current rectification is found in oxygen-substituted zigzag graphyne nanoribbon/hydrogen-terminated zigzag graphene nanoribbon heterostructure junctions, from the application of nonequilibrium Green's function formalism combined with density functional theory. This behavior could be tuned by varying the number and location of oxygen atoms in the zigzag graphyne nanoribbon parts, and the rectification direction could be reversed due to the parity limitation tunneling effect. Moreover, an obvious negative differential resistance behavior is found and may be explained by two different mechanisms.

Impact of MDM2 single nucleotide polymorphism on oral squamous cell carcinoma risk.

Mouse Double Minute 2 (MDM2) has emerged as a pivotal cellular antagonist of p53 by destructing the suppressive function of p53 against tumorigenesis. The MDM2 309 T > G polymorphism has been studied for its association with oral squamous cell carcinoma (OSCC) susceptibility, but the evidence was confusing and inconclusive. Here, we performed a meta-analysis to estimate the effects of the 309 T > G polymorphism on the development of OSCC. The relevant studies were searched on both PubMed and Embase. We estimated the risk of OSCC using odds ratio (OR) and 95 % confidence interval (CI). In addition, between-study heterogeneity was measured by the χ (2)-based statistic test; sensitivity analysis, and the funnel plots and Egger's test were also performed in this meta-analysis. Based on five case-control studies with a total of 1,369 OSCC cases and 2,167 control subjects, the meta-analysis result showed neither increased nor decreased risk of OSCC associated with any genetic model of the 309 T > G polymorphism. Similar results were observed in the subgroup of Asians. No significant heterogeneity and publication bias were detected in the meta-analysis. The evidence provided in our study indicated that the 309 T > G polymorphism might have no significant contribution to susceptibility toward OSCC.

Association of periodontal disease with oral cancer: a meta-analysis.

The objective is to evaluate the association of periodontal disease with the risk of oral cancer. Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model to pool the odds ratio (OR) according to the test of heterogeneity. A total of five eligible studies included 1,191 oral cancer patients and 1,992 healthy control subjects were analyzed. By meta-analysis, we found a significant association of periodontal disease with oral cancer [OR = 3.53, 95 % CI (1.52-8.23); P = 0.003]. Patients with periodontal disease have increased susceptibility to oral cancer.

Peniciketals A-C, new spiroketals from saline soil derived Penicillium raistrichii.

Peniciketals A-C (1-3), three new spiroketals with a benzo-fused 2,8-dioxabicyclo[3.3.1]nonane moiety, were isolated from the saline soil derived fungus Penicillium raistrichii. Their structures including absolute configurations were established by NMR, X-ray diffraction, and ECD calculations. Their cytotoxicities were tested against A549, HL-60, and K562 cell lines, and 1-3 showed the selective effects on HL-60 cells with IC50 values of 3.2, 6.7, and 4.5 µM, respectively.

Effects of disordered interchain interactions on polaron dynamics in semiconducting polymers.

Polaron dynamics in a system of two randomly coupled polymer chains is simulated using a nonadiabatic evolution method. The simulations are performed within the framework of the Su-Schrieffer-Heeger model modified to include disordered interchain interactions and an external electric field. By analysing the polaron velocity statistically, we find that the polaron motion is determined by the competition between the electric field and the disordered interchain interactions. Polaron dynamics are classified into two types, weak-coupling dynamics and strong-coupling dynamics. It is found that the strength of interchain interactions is the dominant factor controlling charge propagation in weak-coupling dynamics, whereas the effects of disorder are dominant in strong-coupling dynamics. The charge carriers tend to have higher mobility for stronger interchain coupling, and interchain coupling disorder can be favorable for charge transport depending on the coupling strength and the electric field.

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro.

AIM: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. METHODS: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPE-LC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-(127)I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC(50)) of sifuvirtide on cell fusion was determined by co-cultivation assay. RESULTS: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 microg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626+/-2886 microg/L and 528+/-191 microg/L, and the terminal elimination half-lives (T(1/2)) were 6.3+/-0.9 h and 5.5+/-1.0 h, respectively. After sc, T(max) was 0.25-2 h, and the absolute bioavailability was 49%+/-13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC(50) of 0.33 microg/L. CONCLUSION: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T(1/2) of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC(50) in vitro.

Reverse polarization in charged pi-conjugated oligomers.

Single-photon excitation in a charged pi-conjugated oligomer is studied theoretically. An apparent reverse polarization is obtained through single-photon excitation, which is different from that obtained through a double-photon excitation. The polarizability is calculated and it is found that a maximum reverse polarization will appear at a suitable conjugation length. In addition, we indicate that the reverse polarization is a nonlinear behavior with the induced electric field. Effects of nondegenerate confinement and interchain interactions on the reverse polarization are also discussed.

[Genetic alteration of p16 gene in oral and maxillofacial squamous cell carcinomas].

OBJECTIVE: To detect p16 gene alteration in oral and maxillofacial squamous cell carcinomas (OMSCC) and its relation with this tumor type. METHODS: To examine 33 paraffin-embedded cases of primary oral and maxillofacial squamous cell carcinoma by PCR-SSCP method and analyze relationship of p16 gene alteration with clinical stages, histological grades, lymphatic metastasis in OMSCC. RESULTS: It revealed 9 of 33(27%) with p16 gene change including 7 (21%) homozygous deletions and 2 (6%) point mutations. There were no significant differences among clinical stage I-IV each other (P>0.05),but there were significant differences between clinical stage I+II and clinical stage III+IV (P<0.05); P16 gene alteration did not significantly differ among histological grading, lymphatic metastasis positive group and negative group in OMSCC. CONCLUSION: Genetic deletion and mutation of p16 gene are frequent molecular events in this kind of tumor, its inactivation has played a important role in the developmental course of OMSCC. p16 gene alteration closely correlates with clinical stages, and the frequency of its alteration may increase following the development of tumor clinical course. The results can be used to evaluate the prognosis and assist in diagnosis of the patients. But no relation with histological grades and lymphatic metastasis which still remains to further study.