KK-LC-1, a biomarker for prognosis of immunotherapy for primary liver cancer.

PURPOSE: There is mounting evidence that patients with liver cancer can benefit from Immune checkpoint inhibitors. However, due to the high cost and low efficacy, we aimed to explore new biomarkers for predicting the efficacy of immunotherapy. METHODS: Specimens and medical records of liver cancer patients treated at Drum Tower Hospital of Nanjing University were collected, and the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in tissues as well as the corresponding antibodies in serum were examined to find biomarkers related to the prognosis of immunotherapy and to explore its mechanism in the development of liver cancer. RESULTS: KK-LC-1 expression was found to be 34.4% in histopathological specimens from 131 patients and was significantly correlated with Foxp3 expression (P = 0.0356). The expression of Foxp3 in the tissues of 24 patients who received immunotherapy was significantly correlated with overall survival (OS) (P = 0.0247), and there was also a tendency for prolonged OS in patients with high expression of KK-LC-1. In addition, the expression of KK-LC-1 antibody in the serum of patients who received immunotherapy with a first efficacy evaluation of stable disease (SD) was significantly higher than those with partial response (PR) (P = 0.0413). CONCLUSIONS: Expression of KK-LC-1 in both tissues and serum has been shown to correlate with the prognosis of patients treated with immunotherapy, and KK-LC-1 is a potential therapeutic target for oncological immunotherapy.

Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted. METHODS: The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified. RESULTS: Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy. CONCLUSIONS: Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.

Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer.

Despite the successful application of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, the treatment efficacy in solid tumors remains unsatisfactory, largely due to the highly immunosuppressive tumor microenvironment and low density of specific tumor antigens. Natural killer group 2 member D (NKG2D) CAR-T cells have shown promising treatment effects on several cancers such as lymphoma and multiple myeloma. However, the application and efficacy of NKG2D-CAR-T cells in gastric cancer (GC) still needs further exploration. This study identified a novel combination immunotherapy strategy with Dickkopf-1 (DKK1) inhibition and NKG2D-CAR-T cells, exerting synergistic and superior antitumor effect in GC. We show that the baseline expression of NKG2D ligands (NKG2DLs) is at low levels in GC tissues from The Cancer Genome Atlas and multiple GC cell lines including NCI-N87, MGC803, HGC27, MKN45, SGC7901, NUGC4, and AGS. In addition, DKK1 inhibition by WAY-262611 reverses the suppressive tumor immune microenvironment (TIME) and upregulates NKG2DL expression levels in both GC cell lines and GC tissues from a xenograft NCG mouse model. DKK1 inhibition in GC cells markedly improves the immune-activating and tumor-killing ability of NKG2D-CAR-T cells as shown by cytotoxicity assays in vitro. Moreover, the combination therapy of NKG2D-CAR-T and WAY-262611 triggers superior antitumor effects in vivo in a xenograft NCG mouse model. In sum, our study reveals the role of DKK1 in remodeling GC TIME and regulating the expression levels of NKG2DLs in GC. We also provide a promising treatment strategy of combining DKK1 inhibition with NKG2D-CAR-T cell therapy, which could bring new breakthroughs for GC immunotherapy.

Piezo-Activated Atomic-Thin Molybdenum Disulfide/MXene Nanoenzyme for Integrated and Efficient Tumor Therapy via Ultrasound-Triggered Schottky Electric Field.

Monolayer molybdenum disulfide (MoS2 ) nanoenzymes exhibit a piezoelectric polarization, which generates reactive oxygen species to inactivate tumors under ultrasonic strain. However, its therapeutic efficiency is far away from satisfactory, due to stackable MoS2 , quenching of piezo-generated charges, and monotherapy. Herein, chitosan-exfoliated monolayer MoS2 (Ch-MS) is composited with atomic-thin MXene, Ti3 C2 (TC), to self-assemble a multimodal nanoplatform, Ti3 C2 -Chitosan-MoS2 (TC@Ch-MS), for tumor inactivation. TC@Ch-MS not only inherits piezoelectricity from monolayer MoS2 , but also maintains remarkable stability. Intrinsic metallic MXene combines with MoS2 to construct an interfacial Schottky heterojunction, facilitating the separation of electron-hole pairs and endowing TC@Ch-MS increase-sensitivity magnetic resonance imaging responding. Schottky interface also leads to peroxidase mimetics with excellent catalytic performance toward H2 O2 in the tumor microenvironment under mechanical vibration. TC@Ch-MS possesses the superior photothermal conversion efficiency than pristine TC under near-infrared ray illumination, attributed to its enhanced interlaminar conductivity. Meanwhile, TC@Ch-MS realizes optimized efficiency on tumor apoptosis with immunotherapy. Therefore, TC@Ch-MS achieves an integrated diagnosis and multimodal treatment nanoplatform, whereas the toxicity to normal tissue cells is negligible. This work may shed fresh light on optimizing the piezoelectric materials in biological applications, and also give prominence to the significance of intrinsic metallicity in MXene.

A delayed spontaneous second-trimester tubo-abdominal pregnancy diagnosed and managed by laparotomy in a "self-identified" infertile woman, a case report and literature review.

BACKGROUND: Abdominal pregnancy, a rare form of ectopic pregnancy, is associated with high morbidity and adverse consequences for future fertility. Early recognition and management reduce mortality and allow minimal invasive and conservative treatment. In modern medicine, primitive prevention to unexpected fatal pregnancies is crucial. CASE PRESENTATION: A divorced 33-year-old "self-identified" infertile polycystic ovary woman diagnosed as repeated implantation failure in previous in vitro fertilization with her ex-husband ever presented in surgery department with a history of 15-day abdominal pain, nausea, and vomiting and 3-h worsening abdominal pain. The serum beta-human chorionic gonadotropin value was more than 10,000 m-international units per milliliter. Sonogram findings were significant for the absence of intrauterine gestation; a placenta and well-formed living fetus of second-trimester gestation were seen in the abdomen, accompanied by hemoperitoneum. A unique spontaneously second-trimester tubo-abdominal pregnancy was confirmed in emergent laparotomy by gynecologists, she received a removing of the living fetus, a right total salpingectomy, resection of partial omentum and blood transfusion. The patient recovered uneventfully and her serum beta-human chorionic gonadotropin returned to normal range on the 30th postoperative day, till now, she has weak fertility awareness because of her catastrophic experiences in the unexpected abdominal pregnancy. CONCLUSIONS: This case highlights woman with a previous in vitro fertilization history may be in is a high risk to be delayed or missed in diagnosis in an intended ectopic pregnancy due to a fixed belief in infertility. Educational interventions and contraceptive care should be provided by fertility and healthcare practitioner. The possibility of abdominal pregnancy must always be suspected and dealt with promptly and appropriately by the astute clinician.

Comparative clinical outcome following individualized follitropin delta dosing in Chinese women undergoing ovarian stimulation for in vitro fertilization /intracytoplasmic sperm injection.

BACKGROUND: To compare the efficacy and safety of follitropin delta in its individualized fixed-dose regimen with follitropin alfa in a conventional adjustable dosing regimen in Chinese women.  METHODS: This was a subgroup analysis of the randomized, multi-center, assessor-blind, non-inferiority trial (GRAPE) including 759 Chinese women (aged 20-40 years) recruited in 16 reproductive medicine clinics in China. Women were randomized in a 1:1 ratio to be treated with either follitropin delta dose based on anti-Müllerian hormone (AMH) and body weight or conventional dosing with follitropin alfa following a gonadotropin-releasing hormone (GnRH) antagonist protocol. The primary outcome was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority margin -10.0%). RESULTS: 378 in the follitropin delta group and 381 in the follitropin alfa group were randomized and exposed. Non-inferiority was confirmed with respect to ongoing pregnancy with rates of 31.0% vs. 25.7% for follitropin delta compared to follitropin alfa, estimated mean difference of 5.1% (95% confidence interval (CI) -1.3% to 11.5%). The clinical pregnancy rate (35.4% vs. 31.5%, P = 0.239) and live birth rate (31.0% vs. 25.5%, P = 0.101) were comparable between the follitropin delta group and the follitropin alfa group. Overall, the individualized follitropin delta treatment resulted in fewer oocytes retrieved compared to follitropin alfa treatment (10.3 ± 6.2 vs. 12.5 ± 7.5, P < 0.001), which was mainly due to fewer oocytes (10.5 ± 6.4 vs. 13.9 ± 7.8) in women with AMH ≥ 15 pmol/L. Accordingly there was a lower incidence of early ovarian hyper-stimulation syndrome (OHSS) and/or preventive interventions (6.1% vs. 11.0%, P = 0.013). A daily follitropin delta dose of 10.2 µg (95% CI: 9.3-11.2 µg) was estimated to provide the same number of oocytes retrieved as a starting dose of 150 IU/d of follitropin alfa. CONCLUSION: Follitropin delta in its individualized fixed-dose regimen showed similar efficacy and improved safety compared with follitropin alfa in a conventional adjustable dosing regimen in Chinese women. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296527.

The association between serum fatty acids and pregnancy in PCOS women undergoing ovulation induction.

BACKGROUND: Long-term dietary fat intake is thought to affect metabolism and pregnancy of polycystic ovary syndrome (PCOS) patients, and the type of fatty acids one consumes plays an important role. Previous studies mostly used questionnaires to analyze the type and proportion of fatty acids. METHODS: This prospective study included 91 PCOS patients. Serum fatty acids were measured by the gas chromatograph-mass spectrometry method before ovulation induction. We compared the fatty acids between the pregnancy group and the nonpregnancy group and explored the influence of the fatty acids on live births and pregnancy loss. RESULTS: Nervonic acid was lower in the pregnancy group than in the nonpregnancy group (0.25% vs. 0.30%, p = .017). The following trans-fatty acids were significantly lower in the pregnancy group than in the nonpregnancy group: trans-10-heptadecenoic acid, trans-vaccenic acid, trans-11-eicosenoic acid, and brassidic acid. The level of polyunsaturated fatty acids in the live birth group was significantly higher than the pregnancy loss group (16.95% vs. 15.10%, p = .039). Among individual PUFAs, the levels of linoleic acid (p = .043), docosapentaenoic acid (p = .024), alpha-linolenic acid (p = .042), and eicosapentaenoic acid (p = .035) were higher in the live birth group than in the pregnancy loss group. After adjusting for infertility duration, age, and body mass index, our findings suggested an inverse association between pregnancy and nervonic acid, trans-10-heptadecenoic acid, trans-vaccenic acid, trans-11-eicosenoic acid, and brassidic acid and pregnancy. CONCLUSIONS: Our findings indicate that polyunsaturated fatty acids are associated with live birth in PCOS patients. Serum trans-fatty acids and nervonic acid might be risk factors for nonpregnancy. The mechanism of the influence of different fatty acids on pregnancy and live birth merits further exploration.

NIR-Activated Multimodal Photothermal/Chemodynamic/Magnetic Resonance Imaging Nanoplatform for Anticancer Therapy by Fe(II) Ions Doped MXenes (Fe-Ti3 C2 ).

2D MXene, Ti3 C2 (TC), has displayed enormous potential in applications in photothermal therapy (PTT), attributing to its biocompatibility and outstanding photothermal conversion capability. However, some tumor ablations are difficult to be realized completely by monotherapy due to the essential defects of monotherapy and intricate tumor microenvironment (TME). In this work, the appropriate doped Fe2+ ions are anchored into the layers of 2D ultrathin TC nanosheets (TC NSs) to synthesize a novel multifunctional nanoshell of Fe(II)-Ti3 C2 (FTC) through interlayer electrostatic adsorption. FTC possesses superior photothermal conversion efficiency (PTCE) than TC NSs, attributing to the enhanced conductivity promoted by interlaminar ferrous ion-channels. Moreover, Fenton reaction based on ferrous ions endows FTC the abilities of reactive oxide species (ROS) releasing and glutathione (GSH) suppression triggered by near-infrared (NIR) laser, featuring splendid biocompatibility and curative effect in hypoxic TME. Meanwhile, magnetic resonance imaging (MRI) responding in FTC reveals the potential as an integrated diagnosis and treatment nanoplatform. FTC could provide new insights into the development of multimoded synergistic nanoplatform for biological applications, especially breaking the shackles of MXenes merely used as a photo-thermal agent (PTA), adopting it to bioimaging sensor and drug loading.

Strangulated internal hernia following severe ovarian hyperstimulation syndrome: a case report.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian stimulation. Herein, we report a rare case of strangulated internal hernia in a woman with severe OHSS following ovulation induction. A delay in the diagnosis and management of acute abdominal pain can lead to serious problems. The aim of this case report was to highlight the diagnostic difficulties of abdominal pain in women with OHSS, and emphasize the positive effects of imaging and a timely differential diagnosis in clinical practice.

Novel compound heterozygous mutation in WEE2 is associated with fertilization failure: case report of an infertile woman and literature review.

BACKGROUND: Fertilization failure after intracytoplasmic sperm injection continues to affect couples and the etiology is not well-understood. CASE PRESENTATION: We characterized a couple with 2-year history of primary unexplained infertility. Three different assisted reproduction attempts (IVF + rescue ICSI, ICSI and ICSI-AOA) showed repeated fertilization failure for MII oocyte retrieval after controlled ovarian hyperstimulation. After whole-exome sequencing and sanger sequencing of the couple and their family members, variant pathogenicity was assessed using SIFT, PolyPhen2, Mutation Taster, and Human Splicing Finder software. We identified novel compound heterozygous mutations, c.1535 + 3A > G and c.946C > T (p. Leu316Phe), in WEE2 in the female proband. Trios analysis of the variations revealed an autosomal recessive pattern. c.1535 + 3A > G in WEE2 was predicted to break the wild-type donor site and affect splicing, and the missense mutation c.946C > T (p. Leu316Phe) of WEE2 was predicted to be pathogenic. CONCLUSION: A novel compound heterozygous mutation in WEE2 was identified in an infertile female who experienced repeated fertilization failure even after ICSI-AOA. These novel mutations in WEE2 provided genetic evidence for fertilization failure.

High level of visfatin and the activation of Akt and ERK1/2 signaling pathways are associated with endometrium malignant transformation in polycystic ovary syndrome.

This study aimed to assess the clinicopathological significance of serum levels and endometrium tissue expression of visfatin in polycystic ovary syndrome (PCOS) patients. A total of 80 PCOS patients and 80 matching controls were included in this study. We analyzed the relationship between the expression of visfatin in endometrium and clinicopathological characteristics in PCOS patients. The correlation between the expression of visfatin and p-Akt, Akt, p-ERK1/2, and ERK1/2 in PCOS tissues was evaluated as well. Visfatin expression in PCOS endometrial tissues were significantly higher than those in controls (p = .001). The expression of phosphorylation of Akt and ERK1/2 were significantly higher in PCOS endometrium tissues compared to controls (p < .05). Moreover, a high expression of tissue visfatin in PCOS tissues was positively correlated with the expression of p-Akt (p = .015), and p-ERK1/2 (p = .013). Western blotting revealed that protein expression of visfatin in PCOS patients with endometrial hyperplasia and cancer was higher than that in patients with normal endometrium tissues, and the difference was statistically significant (p = .027). The expression of p-Akt (p = .018) and p-ERK1/2 (p = .035) in PCOS patients with endometrial hyperplasia and cancer was significantly higher than that in patients with normal endometrium tissues. Visfatin may be a potential biomarker for endometrial malignant transformation in PCOS patients.

Hysteroscopic Resection of Endometrial Polyps and Assisted Reproductive Technology Pregnancy Outcomes Compared with No Treatment: A Systematic Review.

Endometrial polyps are frequently encountered in the uterine cavity of infertile women. There is much debate regarding the treatment of endometrial polyps in patients who are undergoing assisted reproductive technology (ART). A systematic review was performed by searching PubMed, Embase, and the Cochrane Library for retrospective or prospective studies that compared the effect of hysteroscopic resection of polyps with no treatment on pregnancy outcomes of patients who underwent ART. The primary outcomes were clinical pregnancy, live birth, miscarriage, and implantation rates after ART. Eight studies with a total of 2267 patients were included. The results showed that hysteroscopic resection of endometrial polyps (mean size <2 cm) was associated with an increased rate of clinical pregnancy in patients who underwent intrauterine insemination. No clear benefit was observed for clinical pregnancy, live birth, miscarriage, or implantation rates in patients who underwent in vitro fertilization/intracytoplasmic sperm injection cycles. In conclusion, the effect of hysteroscopic polypectomy on pregnancy outcomes of patients who have undergone ART remains unclear. More prospective, randomized controlled trials are warranted to determine appropriate treatment.

Less-invasive chromosome screening of embryos and embryo assessment by genetic studies of DNA in embryo culture medium.

PURPOSE: To perform a preliminary exploration of a new embryo rank in clinical practice by combining the embryo chromosome copy number and mitochondrial copy number analysis of DNA extracted from embryo culture medium and blastocoel fluid. METHOD: Eighty-three ICSI embryos from day 2 or day 3 were cultured to day 5 or day 6. Thirty-two blastocysts of 3 cc or above were obtained. Culture medium and blastocoel fluid were collected at 24 h before blastocyst formation. The genomic DNA and mitochondrial DNA (mtDNA) from the culture medium combined with blastocoel fluid and the whole blastocyst were amplified and sequenced by MALBAC-NGS. We compared the chromosomal information generated by the new protocol from the culture medium and the information employed by the whole embryo method. A multivariable linear regression was performed to study the impact of the blastocyst morphological score, chromosomal abnormality, embryo mtDNA copy number, and female age on the culture medium mtDNA copy number. RESULTS: (1) The DNA from 31 blastocysts was successfully amplified, and the successful amplification rate was 96.9% (31/32). The success rate of the amplification of genomic DNA extracted from the culture medium was 87.5% (28/32). (2) There were 18 blastocysts in which the less invasive method and the whole embryo method revealed the same results. The consistency rate was 66.7% (18/27). (3) The culture medium mitochondrial DNA copy number (MCN) had a significantly positive correlation with the blastocyst mitochondrial DNA copy number (P = 0.001), female age (P = 0.012), and blastocyst score (P = 0.014), but there was no obvious correlation with blastocyst chromosome (P = 0.138). CONCLUSIONS: The preliminary exploration result of the less invasive approach for having an embryo rank was not satisfying, which still awaits further long-term evaluation.

A novel single-stranded RNA virus in Nesidiocoris tenuis.

The complete genome sequence of a novel single-stranded RNA virus in Nesidiocoris tenuis was determined by RNA-seq and rapid amplification of cDNA ends (RACE) methodologies and was named N. tenuis virus 1. The genomic RNA was 3970 nucleotides (nt) in length and contained two putative open reading frames (ORFs). ORF1 encoded a polypeptide with 283 amino acids containing a viral (superfamily 1) RNA helicase (Hel) domain, and ORF2 encoded a polypeptide with 294 amino acids containing an RNA-dependent RNA polymerase (RdRP) domain. Phylogenetic analysis using the deduced amino acid sequences indicated that the N. tenuis virus 1 clustered with Blackford virus; however, the low bootstrap values and unique genomic structure suggested that the virus is a prototype of a new type of unclassified viruses. The prevalence of N. tenuis virus 1 infection in field populations of N. tenuis differed between three locations, with 28.32% of the 113 sampled individuals testing positive for the virus.

[CatSper in sperm hyperactivation and male infertility: Advances in studies].

The CatSper channel is known as one of the most important Ca²âº channels on the cell membrane of mammalian sperm and plays a key role in the motility, hyperactivation and fertilization function of sperm. The CatSper protein, expressed exclusively in the principal piece of the sperm tail, is composed of CatSper1-4 and 5 auxiliary unitsß,γ,δ and ε, and has an essential part in the functional and structural domains of Ca²âºas well as in the spatiotemporal regulation of the P-Tyr protein, sperm hyperactivation, efficient sperm migration in the oviduct, egg penetration, and normal fertility. Recent studies show that functional deficiency of CatSper seriously affects sperm function,and the loss of any one of its 9 subunits may lead to male reproductive dysfunction. This paper outlines recent advances in the studies of the CatSperprotein, focusing on its expression, location, structure, and regulation,as well as itsinfluence on sperm hyperactivation and male reproduction.

Characterization and Distribution Analysis of a Densovirus Infecting Myzus persicae nicotianae (Hemiptera: Aphididae).

Densoviruses (DVs) are a group of viruses that contain a linear single-stranded DNA genome between 4­6 kb in length. Herein, we report a DV with a 5,480-nt genome, isolated from tobacco aphid (Myzus persicae nicotianae Blackman), named MpnDV. Unlike the genome of M. persicae densovirus (MpDV), which possesses five open reading frames (ORFs), the genome of MpnDV contains four putative ORFs­the nonstructural protein 1 (NS1) and NS2 from MpnDV are 98- and 52-amino acids longer than those of MpDV, respectively, at the N-terminus, and the capsid proteins (VP) are 102 amino acids longer at the C-terminus than those of MpDV. Mapping of the MpnDV transcripts by RACE method indicated that the ORF of NS2 started at nt 340 and the right two putative ORFs were combined together by deleting two introns, one of 95 bp located at nt 2,932­3,026 and the other of 145 bp located at nt 4,715­4,859, suggesting transcript mapping was necessary for analyzing of genome organization. Alignment analysis indicated that MpnDV shows 97% sequence identity with MpDV, and that the shortened ORFs resulted from nucleotide indels, suggesting MpnDV and MpDV were two isolates of the same virus. Thus, MpnDV and MpDV clustered together in a tree-based analysis. The prevalence of MpnDV infection in wild populations of tobacco aphids differed among 29 locations; 34% of the 622 individuals sampled were positive. The genome organization, transcript strategy, and widespread distribution in wild populations suggest that MpnDV might possess a biological function different from that of MpDV.

Prevalence and predictors of metabolic abnormalities in Chinese women with PCOS: a cross- sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition estimated to affect 5.61% of Chinese women of reproductive age, but little is known about the prevalence and predictors in Chinese PCOS patients. This study aimed to determine the prevalence and predictors of the metabolic abnormalities in Chinese women with and without PCOS. METHODS: A large-scale national epidemiological investigation was conducted in reproductive age women (19 to 45 years) across China. 833 reproductive aged PCOS women, who participated in the healthcare screening, were recruited from ten provinces in China. Clinical history, ultrasonographic exam (ovarian follicle), hormonal and metabolic parameters were the main outcome measures. RESULTS: The prevalence of metabolic syndrome (MetS) as compared in PCOS and non-PCOS women from community were 18.2% vs 14.7%, and IR (insulin resistance) were 14.2% vs 9.3% (p < 0.001) respectively. After adjusting for age, the indicators (central obesity, hypertension, fasting insulin, SHBG, dyslipinaemia) for metabolic disturbances were significantly higher in PCOS than in non-PCOS groups. Using multivariate logistic regression, central obesity and FAI were risk factors, while SHBG was a protective factor on the occurrence of Mets and IR in PCOS women (OR: 1.132, 1.105 and 0.995). CONCLUSIONS: The risk factors of the metabolic syndrome and insulin resistance were BMI and FAI for PCOS women, respectively. The decrease of SHBG level was also a risk factor for insulin resistance in both PCOS and metabolic disturbance.

Quantum Dots as a Potential Multifunctional Material for the Enhancement of Clinical Diagnosis Strategies and Cancer Treatments.

Quantum dots (QDs) represent a class of nanoscale wide bandgap semiconductors, and are primarily composed of metals, lipids, or polymers. Their unique electronic and optical properties, which stem from their wide bandgap characteristics, offer significant advantages for early cancer detection and treatment. Metal QDs have already demonstrated therapeutic potential in early tumor imaging and therapy. However, biological toxicity has led to the development of various non-functionalized QDs, such as carbon QDs (CQDs), graphene QDs (GQDs), black phosphorus QDs (BPQDs) and perovskite quantum dots (PQDs). To meet the diverse needs of clinical cancer treatment, functionalized QDs with an array of modifications (lipid, protein, organic, and inorganic) have been further developed. These advancements combine the unique material properties of QDs with the targeted capabilities of biological therapy to effectively kill tumors through photodynamic therapy, chemotherapy, immunotherapy, and other means. In addition to tumor-specific therapy, the fluorescence quantum yield of QDs has gradually increased with technological progress, enabling their significant application in both in vivo and in vitro imaging. This review delves into the role of QDs in the development and improvement of clinical cancer treatments, emphasizing their wide bandgap semiconductor properties.

Transition Metal Oxide Nanomaterials: New Weapons to Boost Anti-Tumor Immunity Cycle.

Semiconductor nanomaterials have emerged as a significant factor in the advancement of tumor immunotherapy. This review discusses the potential of transition metal oxide (TMO) nanomaterials in the realm of anti-tumor immune modulation. These binary inorganic semiconductor compounds possess high electron mobility, extended ductility, and strong stability. Apart from being primary thermistor materials, they also serve as potent agents in enhancing the anti-tumor immunity cycle. The diverse metal oxidation states of TMOs result in a range of electronic properties, from metallicity to wide-bandgap insulating behavior. Notably, titanium oxide, manganese oxide, iron oxide, zinc oxide, and copper oxide have garnered interest due to their presence in tumor tissues and potential therapeutic implications. These nanoparticles (NPs) kickstart the tumor immunity cycle by inducing immunogenic cell death (ICD), prompting the release of ICD and tumor-associated antigens (TAAs) and working in conjunction with various therapies to trigger dendritic cell (DC) maturation, T cell response, and infiltration. Furthermore, they can alter the tumor microenvironment (TME) by reprogramming immunosuppressive tumor-associated macrophages into an inflammatory state, thereby impeding tumor growth. This review aims to bring attention to the research community regarding the diversity and significance of TMOs in the tumor immunity cycle, while also underscoring the potential and challenges associated with using TMOs in tumor immunotherapy.

Analyzing the quality differences between healthy and moldy cigar tobacco leaves during the air-curing process through fungal communities and physicochemical components.

Introduction: The air-curing process of cigar tobacco, as a key step in enhancing the quality of cigars, is often susceptible to contamination by mold spores, which severely constrains the quality of cigar tobacco. Methods: This study employed high-throughput Illumina sequencing technology and a continuous flow analysis system to analyze the differences between the microbial communities and physicochemical components of moldy and healthy cigar tobacco leaves. Furthermore, correlation analysis was performed to reveal the impact of mold on the quality of cigar tobacco. Results: The differences between the microbial flora and physicochemical compositions of moldy (MC) and healthy (HC) tobacco leaves were analyzed, revealing significant disparities between the two groups. Aspergillus spp. represented the dominant mold in MC, with nine out of twelve isolated molds showing higher quantities on MC than on HC. Mold contamination notably decreased the total nitrogen (TN), total phosphorus (TP), total alkaloids (TA), starch, protein, and flavor constituents while increasing the total fatty acid esters (TFAA), which was accompanied by a shift towards weakly acidic pH in the leaves. Fungal community analysis indicated a significant reduction in the fungal operational taxonomic unit (OUT) numbers and diversity indices in MC, contrasting with the bacterial trends. Aspergillus exhibited significantly higher relative abundance in MC, with LEfSe analysis pinpointing it as the primary driver of differentiation. Furthermore, significant negative correlations were observed between Aspergillus and TP, starch, TA, and protein, while a significant positive association was evident with TFAA. Network analysis underscored the pivotal role of Aspergillus as the species influencing disparities between HC and MC, with its abundance serving as a critical determinant during the air-curing process. Discussion: This study elucidated substantial quality distinctions between MC and HC during air-curing, with Aspergillus emerging as the key species contributing to leaf mold.