Photo-Enhanced Chemo-Transistor Platform for Ultrasensitive Assay of Small Molecules.

Compared with traditional assay techniques, field-effect transistors (FETs) have advantages such as fast response, high sensitivity, being label-free, and point-of-care detection, while lacking generality to detect a wide range of small molecules since most of them are electrically neutral with a weak doping effect. Here, we demonstrate a photo-enhanced chemo-transistor platform based on a synergistic photo-chemical gating effect in order to overcome the aforementioned limitation. Under light irradiation, accumulated photoelectrons generated from covalent organic frameworks offer a photo-gating modulation, amplifying the response to small molecule adsorption including methylglyoxal, p-nitroaniline, nitrobenzene, aniline, and glyoxal when measuring the photocurrent. We perform testing in buffer, artificial urine, sweat, saliva, and diabetic mouse serum. The limit of detection is down to 10-19 M methylglyoxal, about 5 orders of magnitude lower than existing assay technologies. This work develops a photo-enhanced FET platform to detect small molecules or other neutral species with enhanced sensitivity for applications in fields such as biochemical research, health monitoring, and disease diagnosis.

Association between maternal metabolic profiles in pregnancy, dietary patterns during lactation and breast milk leptin: a retrospective cohort study.

Breast milk leptin plays a potential role in preventing childhood obesity. However, the associations of breast milk leptin with maternal metabolism in pregnancy and dietary patterns during lactation are still unclear. We aimed to explore associations of breast milk leptin with maternal metabolic profiles in pregnancy and dietary patterns during lactation. A total of 332 participants were recruited for this retrospective cohort study. Breast milk samples were collected at approximately 6 weeks postpartum. Breast milk leptin and twenty-three metabolic profiles in pregnancy were measured in this study. A semi-quantitative FFQ was used to gather dietary information during lactation. Both principal component analysis and the diet balance index were used to derive dietary patterns. Among twenty-three maternal metabolic profiles, maternal serum glucose (ß = 1·61, P = 0·009), γ-glutamyl transferase (ß = 0·32, P = 0·047) and albumin (ß = -2·96, P = 0·044) in pregnancy were correlated with breast milk leptin. All dietary patterns were associated with breast milk leptin. Given the joint effects of maternal metabolism in pregnancy and dietary patterns during lactation, only diet quality distance was significantly associated with leptin concentrations in breast milk (low level v. almost no diet problem: ß = -0·46, P = 0·011; moderate/high level v. almost no diet problem: ß = -0·43, P = 0·035). In conclusion, both maternal metabolism in pregnancy and dietary patterns during lactation were associated with breast milk leptin. Maternal diet balance during lactation was helpful to improve breast milk leptin concentration.

A novel embryo biopsy morphological analysis and genetic integrality criterion system significantly improves the outcome of preimplantation genetic testing.

PURPOSE: While efforts have been made to establish blastocyst grading systems in the past decades, little research has examined the quality of biopsy specimens. This study is the first to correlate the morphology of biopsied trophectoderm (TE) cells to their quality and subsequent genetic testing results of preimplantation genetic testing (PGT), through an innovative Morphological Analysis and Genetic Integrality Criterion (MAGIC) system. METHODS: Biopsied TE cells were first evaluated according to the MAGIC procedure, followed by whole-genome amplification (WGA) and library construction, and then sequenced using the Illumina X Ten Platform. Copy number variation (CNV) and allele drop-out (ADO) rates as well as test failure rates were compared and analyzed. RESULTS: Our data explores the relationship between TE cell morphology and its quality and final genetic testing outcome, which is established based on the MAGIC system. MAGIC guarantees that only high- or good-quality TE cells are used for genetic testing to generate excellent data uniformity and lower ADO rates. Low-quality cells containing biopsied TE cell mass are responsible for the "background noise" of CNV analysis. CONCLUSION: The MAGIC application has effectively decreased the false-positive mosaicism, hence to ensure the stability and veracity of detection results, to avoid misdiagnoses, and to improve accuracy, as well as to avoid re-biopsy procedures. The study also contributes to understand how the IVF laboratory and the molecular biology laboratory depend on each other to achieve good-quality PGT results, which are clinically relevant for the patients.

The function of Nucleoporin 37 on mouse oocyte maturation and preimplantation embryo development.

PURPOSE: Nucleoporin 37 (NUP37) has been reported to activate the YAP-TEAD signaling, which is crucial for early embryo development. However, whether NUP37 is involved in oocyte meiosis and embryo development remains largely unknown. The study aimed to clarify the function of Nup37 in oocyte maturation and early embryo development, and to explore the mechanism. METHODS: The expression level and subcellular localization of NUP37 were explored. After knocking down of Nup37 by microinjecting interfering RNA (siRNA), the oocyte maturation rate, aberrant PB1 extrusion rate, and blastocyst formation rate were evaluated. In addition, the effect of the downregulation of Nup37 on YAP-TEAD signaling was confirmed by immunofluorescence staining and real-time quantitative PCR. RESULTS: NUP37 was highly expressed in oocytes and early embryos; it mainly localized to the nuclear periphery at mice GV stage oocytes and early embryos. Nup37 depletion led to aberrant PB1 extrusion at the MII stage oocyte and a decreased blastocyst formation rate. The reduction of NUP37 caused YAP1 mislocalization and decreased the expression of Tead1, Tead2, and Tead4 during mice embryo development, thus affecting the YAP-TEAD activity and embryo developmental competence. CONCLUSIONS: In summary, NUP37 played an important role in mice oocyte maturation and preimplantation embryo development.

Direct SARS-CoV-2 Nucleic Acid Detection by Y-Shaped DNA Dual-Probe Transistor Assay.

Rapid screening of infected individuals from a large population is an effective means in epidemiology, especially to contain outbreaks such as COVID-19. The gold standard assays for COVID-19 diagnostics are mainly based on the reverse transcription polymerase chain reaction, which mismatches the requirements for wide-population screening due to time-consuming nucleic acid extraction and amplification procedures. Here, we report a direct nucleic acid assay by using a graphene field-effect transistor (g-FET) with Y-shaped DNA dual probes (Y-dual probes). The assay relies on Y-dual probes modified on g-FET simultaneously targeting ORF1ab and N genes of SARS-CoV-2 nucleic acid, enabling high a recognition ratio and a limit of detection (0.03 copy µL-1) 1-2 orders of magnitude lower than existing nucleic acid assays. The assay realizes the fastest nucleic acid testing (∼1 min) and achieves direct 5-in-1 pooled testing for the first time. Owing to its rapid, ultrasensitive, easily operated features as well as capability in pooled testing, it holds great promise as a comprehensive tool for population-wide screening of COVID-19 and other epidemics.

The methylome of a human polar body reflects that of its sibling oocyte and its aberrance may indicate poor embryo development.

STUDY QUESTION: Is it possible to evaluate the methylome of individual oocytes to investigate the DNA methylome alterations in metaphase II (MII) oocytes with reduced embryo developmental potential? SUMMARY ANSWER: The DNA methylome of each human first polar body (PB1) closely mirrored that of its sibling MII oocyte; hypermethylated long interspersed nuclear element (LINE) and long terminal repeats (LTRs) and methylation aberrations in PB1 promoter regions may indicate poor embryo development. WHAT IS KNOWN ALREADY: The developmental potential of an embryo is determined by the oocyte's developmental competence, and the PB1 is a good substitute to examine the chromosomal status of the corresponding oocyte. However, DNA methylation, a key epigenetic modification, also regulates gene expression and embryo development. STUDY DESIGN, SIZE, DURATION: Twelve pairs of PB1s and sibling MII oocytes were biopsied and sequenced to compare their methylomes. To further investigate the methylome of PB1s and the potential epigenetic factors that may affect oocyte quality, MII oocytes (n = 74) were fertilized through ICSI, while PB1s were biopsied and profiled to measure DNA methylation. The corresponding embryos were further cultured to track their development potential. The oocytes and sperm samples used in this study were donated by healthy volunteers with signed informed consent. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single-cell methylome sequencing was applied to obtain the DNA methylation profiles of PB1s and oocytes. The DNA methylome of PB1s was compared between the respective group of oocytes that progressed to blastocysts and the group of oocytes that failed to develop. DNA methylation levels of corresponding regions and differentially methylated regions were calculated using customized Perl and R scripts. RNA-seq data were downloaded from a previously published paper and reanalysed. MAIN RESULTS AND THE ROLE OF CHANCE: The results from PB1-MII oocyte pair validated that PB1 contains nearly the same methylome (average Pearson correlation is 0.92) with sibling MII oocyte. LINE and LTR expression increased markedly after fertilization. Moreover, the DNA methylation levels in LINE (including LINE1 and LINE2) and LTR were significantly higher in the PB1s of embryos that could not reach the blastocyst stage (Wilcoxon-Matt-Whitney test, P < 0.05). DNA methylation in PB1 promoters correlated negatively with gene expression of MII oocyte. Regarding the methylation status of the promoter regions, 66 genes were hypermethylated in the developmental arrested group, with their related functions (significantly enriched in several Gene Ontology terms) including transcription, positive regulation of adenylate cyclase activity, mitogen-activated protein kinase (MAPK) cascade and intracellular oestrogen receptor signalling pathway. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Data analysis performed in this study focused on the competence of human oocytes and compared them with maternal genetic and epigenetic profiles. Therefore, data regarding the potential regulatory roles of paternal genomes in embryo development are lacking. WIDER IMPLICATIONS OF THE FINDINGS: The results from PB1-oocyte pairs demonstrated that PB1s shared similar methylomes with their sibling oocytes. The selection of the good embryos for transfer should not only rely on morphology but also consider the DNA methylation of the corresponding PB1 and therefore MII oocyte. The application of early-stage analysis of PB1 offers an option for high-quality oocyte and embryo selection, which provides an additional tool for elective single embryo transfer in assisted reproduction. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2018YFC1004003, 2017YFA0103801), the National Natural Science Foundation of China (81730038, 3187144, 81521002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020703). The authors have no conflicts of interest to declare.

Template-Induced Structuring and Tunable Polymorphism of Three-Dimensionally Ordered Mesoporous (3DOm) Metal Oxides.

Convectively assembled colloidal crystal templates, composed of size-tunable (ca. 15-50 nm) silica (SiO2) nanoparticles, enable versatile sacrificial templating of three-dimensionally ordered mesoporous (3DOm) metal oxides (MOx) at both mesoscopic and microscopic size scales. Specifically, we show for titania (TiO2) and zirconia (ZrO2) how this approach not only enables the engineering of the mesopore size, pore volume, and surface area but can also be leveraged to tune the crystallite polymorphism of the resulting 3DOm metal oxides. Template-mediated volumetric (i.e., interstitial) effects and interfacial factors are shown to preserve the metastable crystalline polymorphs of each corresponding 3DOm oxide (i.e., anatase TiO2 (A-TiO2) and tetragonal ZrO2 (t-ZrO2)) during high-temperature calcination. Mechanistic investigations suggest that this polymorph stabilization is derived from the combined effects of the template-replica (MOx/SiO2) interface and simultaneous interstitial confinement that limit the degree of coarsening during high-temperature calcination of the template-replica composite. The result is the identification of a facile yet versatile templating strategy for realizing 3DOm oxides with (i) surface areas that are more than an order of magnitude larger than untemplated control samples, (ii) pore diameters and volumes that can be tuned across a continuum of size scales, and (iii) selectable polymorphism.

Multimodal Neuronavigation in Microsurgery Resection of BrainStem Tumors.

BACKGROUND: Microsurgery is a common treatment of brainstem tumors. However, misdirection, vascular damage, nerves injuries, paralysis, even death are all well-known complications, and the risk of adverse events is more likely in less experienced operators. This study was aimed to validate the accuracy of multimodal neuronavigation during microsurgery resection of brainstem tumors. METHODS: Ten patients with brainstem tumors underwent preoperative MRI, diffusion tensor imaging, computed tomography, three-dimensional print, and images loaded into the neuronavigation platform were used for its segmentation and preoperative planning. After patients' registration and subsequent surgical exposure, each segmented brain element was validated by manual placement of the navigation probe to the target. RESULTS: Preoperative images of the brain matched with three-dimensional print and neuronavigation played important role in all patients. Excellent correspondence between image-based segmentation and microscope view was also evident at the surface of tumors and at the tumor-normal gland interfaces. CONCLUSION: Multimodal navigation is a safe and effective method in surgery for patients with brain stem tumors. Our preliminary study is conducted to encourage for future more research with larger numbers of patients.

The Construction of a Lattice Image and Dislocation Analysis in High-Resolution Characterizations Based on Diffraction Extinctions.

This paper introduces a method for high-resolution lattice image reconstruction and dislocation analysis based on diffraction extinction. The approach primarily involves locating extinction spots in the Fourier transform spectrum (reciprocal space) and constructing corresponding diffraction wave functions. By the coherent combination of diffraction and transmission waves, the lattice image of the extinction planes is reconstructed. This lattice image is then used for dislocation localization, enabling the observation and analysis of crystal planes that exhibit electron diffraction extinction effects and atomic jump arrangements during high-resolution transmission electron microscopy (HRTEM) characterization. Furthermore, due to the method's effectiveness in localizing dislocations, it offers a unique advantage when analyzing high-resolution images with relatively poor quality. The feasibility of this method is theoretically demonstrated in this paper. Additionally, the method was successfully applied to observed edge dislocations, such as 1/6[211-], 1/6[2-11-], and 1/2[01-1], which are not easily observable in conventional HRTEM characterization processes, in electro-deposited Cu thin films. The Burgers vectors were determined. Moreover, this paper also attempted to observe screw dislocations that are challenging to observe in high-resolution transmission electron microscopy. By shifting a pair of diffraction extinction spots and superimposing the reconstructed images before and after the shift, screw dislocations with a Burgers vector of 1/2[011-] were successfully observed in electro-deposited Cu thin films.

LINC00460-FUS-MYC feedback loop drives breast cancer metastasis and doxorubicin resistance.

Therapeutic resistance and metastasis largely contribute to mortality from breast cancer and therefore understanding the underlying mechanisms of such remains an urgent challenge. By cross-analysis of TCGA and GEO databases, LINC00460 was identified as an oncogenic long non-coding RNA, highly expressed in Doxorubicin resistant breast cancer. LINC00460 was further demonstrated to promote stem cell-like and epithelial-mesenchymal transition (EMT) characteristics in breast cancer cells. LINC00460 interacts with FUS protein with consequent enhanced stabilization, which further promotes MYC mRNA maturation. LINC00460 expression was transcriptionally enhanced by c-MYC protein, forming a positive feedback loop to promote metastasis and Doxorubicin resistance. LINC00460 depletion in Doxorubicin-resistant breast cancer cells restored sensitivity to Doxorubicin and increased the efficacy of c-MYC inhibitor therapy. Collectively, these findings implicate LINC00460 as a promising prognostic biomarker and potential therapeutic target to overcome Doxorubicin resistance in breast cancer.

Characteristics of intestinal microbiota in infants with late-onset breast milk jaundice.

Introduction: In this paper, microbiota analysis was determined to analyze the structure and difference of intestinal microbiota between LBMJ (late-onset breast milk jaundice) infants and healthy individuals. Methods: We collected fresh fecal samples from 13 infants with LBMJ and 13 healthy individuals, then determined the intestinal microbiota by 16 s rRNA sequencing. The differences of microbiota structure, diversity and functional characteristics between the two groups were analyzed, and the correlation between dominant genus and TcB (transcutaneous bilirubin) value was calculated. Results: In this study, there were no significant differences in maternal demographic characteristics, neonatal status and macronutrients in breast milk between the two groups (p > 0.05). There are differences in the structure of intestinal microbiota between LBMJ and the control group. At the genus level, the relative abundance of Klebsiella in the case group is high (p < 0.05). At the same time, correlation analysis indicates that the abundance of Klebsiella is positively correlated with TcB value. The intestinal microbiota richness and diversity (Alpha diversity and Beta diversity) of the two groups were significantly different (p < 0.05). LEfSe analysis showed that 25 genera including Klebsiella was significantly enriched in the LBMJ infants, and the other 17 species are enriched in the control group. Functional prediction analysis indicated that 42 metabolic pathways may be related to the occurrence of LBMJ. Conclusion: In conclusion, characteristic changes are seen in intestinal microbiota compositions between LBMJ infants and the healthy controls. Klebsiella is closely associated with the severity of the disease, which may be due to enhanced ß-glucuronidase activity.

Strain in Copper/Ceria Heterostructure Promotes Electrosynthesis of Multicarbon Products.

Elastic strains in metallic catalysts induce enhanced selectivity for carbon dioxide reduction (CO2R) toward valuable multicarbon (C2+) products. However, under working conditions, the structure of catalysts inevitably undergoes reconstruction, hardly retaining the initial strain. Herein, we present a metal/metal oxide synthetic strategy to introduce and maintain the tensile strain in a copper/ceria heterostructure, enabled by the presence of a thin interface layer of Cu2O/CeO2. The tensile strain in the copper domain and deficient electron environment around interfacial Cu sites resulted in strengthened adsorption of carbonaceous intermediates and promoted *CO dimerization. The strain effect in the copper/ceria heterostructure leads to an improved C2+ selectivity with a maximum Faradaic efficiency of 76.4% and a half-cell power conversion efficiency of 49.1%. The fundamental insights gained from this system can facilitate the rational design of heterostructure catalysts for CO2R.

Effect of Carbohydrate-Restricted Dietary Pattern on Insulin Treatment Rate, Lipid Metabolism and Nutritional Status in Pregnant Women with Gestational Diabetes in Beijing, China.

Carbohydrates play an important role in blood glucose control in pregnant women with GDM. Carbohydrate-restricted dietary (CRD) pattern for gestational diabetes mellitus (GDM) has been widely used in clinics, but the change in insulin utilization rate beyond CRD intervention in GDM remains unclear. The aim of the present study was to explore the application of insulin in pregnancy with GDM, as well as the influence of CRD pattern on lipid metabolism and nutritional state. A retrospective study of 265 women with GDM who delivered in Peking University People's Hospital from July 2018 to January 2020 was conducted using a questionnaire survey. Women were divided into a CRD group or a control group according to whether they had received CRD intervention during pregnancy. There was no statistically significant difference in the rate of insulin therapy between the two groups (p > 0.05), the initial gestational week of the CRD group combined with insulin treatment was significantly higher than that of the control group (p < 0.05), and the risk of insulin therapy was positively correlated with fasting plasma glucose (FPG) in early pregnancy (p < 0.05). The incidence of abnormal low-density lipoprotein cholesterol levels in the CRD group was significantly lower than that in the control group (p < 0.05). There were no significant differences in nutritional indexes between the two groups. The results indicate that CRD intervention may be effective in delaying the use of insulin and improving the blood lipids metabolism during GDM pregnancy, while nutritional status may not be significantly affected under CRD intervention, and a high FPG in early pregnancy with GDM may be a risk factor for combined insulin therapy with CRD intervention.

Exploring the role of autophagy during early human embryonic development through single-cell transcriptome and methylome analyses.

Early human embryogenesis is a very sophisticated process due to its unique gene regulatory network. Autophagy has been suggested to play an important role in mediating the development of early embryonic cells in mammals. However, evidence showing how autophagy regulates early human embryogenesis remains to be further explored. In this study, we systematically investigated the human transcriptome and methylome patterns of autophagy-related (ATG) genes in early embryonic cells at single-cell resolution. We analyzed the transcriptomic data of 365 cells and methylome data of 265 cells. The results showed that most ATG genes remained epigenetically active and were expressed stably throughout early embryogenesis, whereas the dynamics varied among different developmental stages. This evidence indicated that the autophagy pathway was constitutively activated and exerted a fundamental role in early human embryo development. Our work, for the first time, comprehensively reveals the features of autophagy during early human embryo development.

Impact of maternal nutrition during early pregnancy and diet during lactation on lactoferrin in mature breast milk.

OBJECTIVE: Lactoferrin supplementation is a promising strategy to prevent infections in neonates. Exploring whether maternal nutritional status in early pregnancy and maternal diet during lactation are associated with lactoferrin concentrations in mature human milk can provide early warning and allow timely adjustment. METHODS: In this follow-up cohort study, 206 participants were recruited at Peking University People's Hospital from June 2018 to June 2019. The levels of albumin and thyroid-stimulating hormones (TSH) were determined as nutritional indicators during early pregnancy. Information on maternal diet during lactation was collected with a semiquantitative food frequency questionnaire, and the lactoferrin concentrations in breast milk were examined at around 42 d postpartum. RESULTS: The median level (interquartile range) of lactoferrin in breast milk was 2844.2 (2568.1, 3103.1) µg/mL. Overall, 5.5% of participants had lower albumin (<40 g/L), and 21.6% had elevated TSH (>2.5 mIU/L), respectively. The concentration of lactoferrin was higher (216.8 [13.4, 420.2] µg/mL) in women with lower albumin levels than in those with normal levels, and elevated TSH had no effect. A 1 g increase in egg intake led to a 0.3 (0.0, 0.6) µg/mL increase in lactoferrin concentration. Lactoferrin levels were also affected by intake of energy, protein, cholesterol, and vitamin A. CONCLUSIONS: Women with lower albumin levels in early pregnancy had higher levels of lactoferrin in mature breast milk. TSH was not related to lactoferrin levels. Intake of energy, protein, cholesterol, and vitamin A may have contributed to lactoferrin concentrations in milk, and egg intake was positively associated with lactoferrin.

Effect of Epidermal Growth Factor in Human Milk and Maternal Diet on Late-Onset Breast Milk Jaundice: A Case-Control Study in Beijing.

Breast milk is crucial in the development of late-onset breast milk jaundice (BMJ), possibly due to the composition of breast milk and the lactating mother's diet. To explore the possible nutritional pathogenesis of late-onset BMJ, we investigated the lactation diet and collected breast milk by following the 42-day postpartum mother−infants pairs in Beijing and a total of 94 pairs were enrolled. The macronutrient content of breast milk was measured, and the epidermal growth factor (EGF) content in breast milk was determined by ELISA. Data on in-hospital and out-of-hospital breastfeeding, infant growth, jaundice-related vaccination, and puerperium diet were collected. The BMJ group received the second dose of hepatitis B vaccine later than the control group, and the difference was statistically significant (p < 0.001). The EGF concentration in breast milk was lower in the BMJ group than in the control group (p = 0.03). When EGF increased by 1 ng/mL, the transcutaneous bilirubin (TcB) value decreased by 0.33 ng/mL and 0.27 ng/mL before and after the adjustment, respectively. A 1 g increase in oil intake led to a 0.38 ng/mL increase in EGF concentration before the adjustment. With a 1 g increase in oil intake, the TcB value decreased by 0.27 ng/mL before the adjustment, and with a 1 g increase in soybean and soybean product intake, the TcB value decreased by 0.34 ng/mL after the adjustment. Collectively, EGF in breast milk may inhibit the occurrence of late-onset BMJ, and the dietary intake of oil in lactating mothers may affect the level of EGF in breast milk, thus affecting the occurrence of late-onset BMJ. Finally, dietary oil intake may be a protective factor for the occurrence of late-onset BMJ by increasing EGF levels in breast milk.

Analysis of the Estrogen Receptor-Associated LncRNA Landscape Identifies a Role for ERLC1 in Breast Cancer Progression.

Estrogen receptor alpha (ERα) plays a vital role in the development of normal breast tissue and in breast cancer. By cross-analyzing The Cancer Genome Atlas (TCGA) database, ERα-regulated long noncoding RNA 1 (ERLC1) was identified as a long noncoding RNA exhibiting a strong association with ERα signaling and high specificity of expression in breast tissue. ERLC1 was transcriptionally activated by ERα, and ERLC1 stabilized the ESR1 transcript by sequestering miR-129 and tethering FXR1 to maintain a positive feedback loop that potentiated ERα signaling. ERLC1 was elevated in tamoxifen-resistant breast cancer cells, where ERLC1 depletion restored sensitivity to tamoxifen and increased the efficacy of palbociclib or fulvestrant therapy. Collectively, these data warrant further investigation of ERLC1 as a modulator of therapeutic response and potential therapeutic target in ER+ breast cancer. SIGNIFICANCE: This study identifies an estrogen-regulated lncRNA and the mechanism by which it positively regulates ERα activity, demonstrating a feedback loop that can promote resistance to antiestrogen therapies in ER+ breast cancer.

Efficacy and mechanism of osimertinib combined with bevacizumab in the treatment of postoperative EGFR positive stage II-IIIA lung adenocarcinoma.

OBJECTIVE: To explore the efficacy and mechanism of osimertinib combined with bevacizumab in treating postoperative epidermal growth factor receptor (EGFR) positive stage II-IIIA lung adenocarcinoma. METHODS: In this retrospective study, one hundred and thirty patients with postoperative EGFR positive stage II-IIIA lung adenocarcinoma were divided into two groups according to different treatment methods. Patients treated with osimertinib alone were included in the single group (65 patients). Patients treated with bevacizumab on the basis of the single group were included in the joint group (65 patients). The short-term efficacy, side effects and survival results of the two groups were counted. The changes of serum vascular endothelial growth factor, serum tumor markers and life quality before and after the treatment were observed. RESULTS: The ORR (66.15%) and DCR (86.15%) in the joint group were significantly higher than those in the single group (47.69% and 70.77%) (both P<0.05). The serum levels of VEGFA, VEGFB, VEGFC, BFGF, HDGF, SDF-1, CEA, CA153, CYFRA21-1 and CA199 in the joint group were lower than those in the single group after the treatment (all P<0.05). No significant difference was shown in the incidence of adverse reactions such as rash, diarrhea, constipation, albuminuria, hypertension and interstitial pneumonia between the joint group and the single group (all P>0.05). After the treatment, the ZPS score of the joint group was lower than that of the single group, and the KPS score was higher than that of the single group (both P<0.05). There was no significant difference in the two-year median DFS and the one or two-year DFS rate between the joint group and the single group (all P>0.05). CONCLUSION: Osimertinib combined with bevacizumab in the treatment of postoperative EGFR positive stage II-IIIA lung adenocarcinoma has evident short-term efficacy and mild side effects, which is helpful in improving the disease control rate and life quality. The mechanism may be related to the regulation of serum CEA, CA153, CYFRA21-1, CA199 levels and inhibition of VEGFA, VEGFB, VEGFC, BFGF, HDGF, and SDF-1 levels.

An Alternatively Spliced p62 Isoform Confers Resistance to Chemotherapy in Breast Cancer.

Resistance to chemotherapy remains a major obstacle to the successful treatment of breast cancer. More than 80% of patients who receive neoadjuvant chemotherapy (NAC) do not achieve a pathologic complete response. In this study, we report a novel p62 mRNA isoform with a short 3'-UTR (untranslated region; p62-SU, 662-nt) that is associated with chemoresistance in breast cancer cells and tissue specimens. The p62 mRNA isoform was identified by RNA sequencing with qRT-PCR, 3'-RACE, and Northern blot analysis. In vitro and in vivo, ectopic expression of p62-SU promoted breast cancer cell proliferation, migration, invasion, and chemoresistance compared with the p62 mRNA isoform with a full-length 3'-UTR (p62-LU, 1,485-nt). Mechanistically, cleavage and polyadenylation specific factor 1 (CPSF1) modulated the 3'-UTR of p62 through alternative polyadenylation. In addition, p62-SU escaped miR-124-3p-mediated repression and upregulated p62-SU protein expression, thereby inducing p62-dependent chemoresistance. These data suggest that a CPSF1-p62-miR-124-3p signaling axis is responsible for reduced sensitivity of breast cancer to chemotherapy. SIGNIFICANCE: Resistance to NAC in breast cancer is driven by a novel p62 mRNA isoform that escapes miRNA-mediated repression and leads to increased p62 protein expression.

Short-wavelength ultraviolet dosimeters based on DNA nanostructure-modified graphene field-effect transistors.

Direct and sensitive short-wavelength ultraviolet (UVC) dosimeters could provide a safer disinfection environment against viruses. We developed direct, quantitative, specific and highly sensitive UVC dosimeters based on DNA nanostructure-modified graphene field-effect transistors. Detectable doses of the dosimeters range from 0.005 to 6 kJ m-2 and such dosimeters have at least 5 times better sensitivity than the current direct UV dosimeters.