Role of interatrial block in modulating cryptogenic stroke risk in patients with patent foramen ovale: a retrospective study.

BACKGROUND: The patent foramen ovale (PFO) and interatrial block (IAB) are associated with cryptogenic stroke (CS). However, the role of the interaction between PFO and IAB in CS remains unclear. METHODS: This case-control study enrolled 256 patients with CS and 156 individuals without a history of stroke or transient ischemic attack. IAB was defined as P wave duration > 120 ms. PFO was evaluated by contrast transesophageal echocardiography, and classified as no-PFO, low-risk PFO and high-risk PFO. Multiplicative and additive interaction analysis were used to assess the interaction between PFO and IAB in CS. RESULTS: Multiplicative interaction analysis unveiled a significant interaction between IAB and low-risk PFO in CS (OR for interaction = 3.653, 95% CI, 1.115-12.506; P = 0.037). Additive interaction analysis indicated that 68.4% (95% CI, 0.333-1.050; P < 0.001) of the increased risk of CS related to low-risk PFO was attributed to the interaction with IAB. The results were robust in multivariate analysis. However, but no significant multiplicative or additive interaction was observed between IAB and high-risk PFO. When stratified by IAB, high-risk PFO was associated with CS in both patients with IAB (OR, 4.186; 95% CI, 1.617-10.839; P = 0.003) and without IAB (OR, 3.476; 95% CI, 1.790-6.750; P < 0.001). However, low-risk PFO was only associated with CS in patients with IAB (OR, 2.684; 95% CI, 1.007-7.149; P = 0.048) but not in those without IAB (OR, 0.753; 95% CI, 0.343-1.651; P = 0.479). CONCLUSION: The interaction between IAB and PFO might play an important role in CS, particularly in cases with low-risk PFO.

Pixel-Level Domain Adaptation: A New Perspective for Enhancing Weakly Supervised Semantic Segmentation.

Recent attention has been devoted to the pursuit of learning semantic segmentation models exclusively from image tags, a paradigm known as image-level Weakly Supervised Semantic Segmentation (WSSS). Existing attempts adopt the Class Activation Maps (CAMs) as priors to mine object regions yet observe the imbalanced activation issue, where only the most discriminative object parts are located. In this paper, we argue that the distribution discrepancy between the discriminative and the non-discriminative parts of objects prevents the model from producing complete and precise pseudo masks as ground truths. For this purpose, we propose a Pixel-Level Domain Adaptation (PLDA) method to encourage the model in learning pixel-wise domain-invariant features. Specifically, a multi-head domain classifier trained adversarially with the feature extraction is introduced to promote the emergence of pixel features that are invariant with respect to the shift between the source (i.e., the discriminative object parts) and the target (i.e., the non-discriminative object parts) domains. In addition, we come up with a Confident Pseudo-Supervision strategy to guarantee the discriminative ability of each pixel for the segmentation task, which serves as a complement to the intra-image domain adversarial training. Our method is conceptually simple, intuitive and can be easily integrated into existing WSSS methods. Taking several strong baseline models as instances, we experimentally demonstrate the effectiveness of our approach under a wide range of settings.

The intersection of the nervous system and breast cancer.

Breast cancer (BC) represents a paradigm of heterogeneity, manifesting as a spectrum of molecular subtypes with divergent clinical trajectories. It is fundamentally characterized by the aberrant proliferation of malignant cells within breast tissue, a process modulated by a myriad of factors that govern its progression. Recent endeavors outline the interplay between BC and the nervous system, illuminate the complex symbiosis between neural structures and neoplastic cells, and elucidate nerve dependence as a cornerstone of BC progression. This includes the neural modulations on immune response, neurovascular formation, and multisystem interactions. Such insights have unveiled the critical impact of neural elements on tumor dynamics and patient prognosis. This revelation beckons a deeper exploration into the neuro-oncological interface, potentially unlocking novel therapeutic vistas. This review endeavors to delineate the intricate mechanisms between the nervous system and BC, aiming to accentuate the implications and therapeutic strategies of this intersection for tumor evolution and the formulation of innovative therapeutic approaches.

Suppressing Organic Bromine but Promoting Bromate: Is the Ultraviolet/Ozone Process a Double-Edged Sword for the Toxicity of Wastewater to Mammalian Cells?

Brominated byproducts and toxicity generation are critical issues for ozone application to wastewater containing bromide. This study demonstrated that ultraviolet/ozone (UV/O3, 100 mJ/cm2, 1 mg-O3/mg-DOC) reduced the cytotoxicity of wastewater from 14.2 mg of pentol/L produced by ozonation to 4.3 mg of pentol/L (1 mg/L bromide, pH 7.0). The genotoxicity was also reduced from 1.65 to 0.17 µg-4-NQO/L by UV/O3. Compared with that of O3 alone, adsorbable organic bromine was reduced from 25.8 to 5.3 µg/L by UV/O3, but bromate increased from 32.9 to 71.4 µg/L. The UV/O3 process enhanced the removal of pre-existing precursors (highly unsaturated and phenolic compounds and poly aromatic hydrocarbons), while new precursors were generated, yet the combined effect of UV/O3 on precursors did not result in a significant change in toxicity. Instead, UV radiation inhibited HOBr concentration through both rapid O3 decomposition to reduce HOBr production and decomposition of the formed HOBr, thus suppressing the AOBr formation. However, the hydroxyl radical-dominated pathway in UV/O3 led to a significant increase of bromate. Considering both organic bromine and bromate, the UV/O3 process effectively controlled both cytotoxicity and genotoxicity of wastewater to mammalian cells, even though an emphasis should be also placed on managing elevated bromate. Futhermore, other end points are needed to evaluate the toxicity outcomes of the UV/O3 process.

Feasibility of Using Magnetic Resonance Spectroscopy Test Biomarkers to Diagnose Alzheimer's Disease: Systematic Evaluation and Meta-Analysis.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, resulting in impairments in memory, cognition, decision-making, and social skills. Thus, accurate preclinical diagnosis of Alzheimer's disease is paramount. The identification of biomarkers for Alzheimer's disease through magnetic resonance spectroscopy (MRS) represents a novel adjunctive diagnostic approach. OBJECTIVE: This study conducted a meta-analysis of the diagnostic results of this technology to explore its feasibility and accuracy. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched without restrictions, with the search period extending up to July 31, 2022. The search strategy employed a combination of subject headings and keywords. All retrieved documents underwent screening by two researchers, who selected them for meta-analysis. The included literature was analyzed using Review Manager 5.4 software, with corresponding bias maps, forest plots, and summary receiver operating characteristic (SROC) curves generated and analyzed. RESULTS: A total of 344 articles were retrieved initially, with 11 articles meeting the criteria for inclusion in the analysis. The analysis encompassed data from approximately 1766 patients. In the forest plot, both sensitivity (95% CI) and specificity (95% CI) approached 1. Examining the true positive rate, false positive rate, true negative rate, and false negative rate, all studies on the summary receiver operating characteristic (SROC) curve clustered in the upper left quadrant, suggesting a very high accuracy of biomarkers detected by MRS for diagnosing Alzheimer's disease. CONCLUSION: The detection of biomarkers by MRS demonstrates feasibility and high accuracy in diagnosing AD. This technology holds promise for widespread adoption in the clinical diagnosis of AD in the future.

Synergistic etching of nickel foam by Fe3+ and Cl- ions to synthesize nickel-iron-layered double hydroxide nanolayers with abundant oxygen vacancies for superior urea oxidation.

Urea electrolysis is an appealing topic for hydrogen production due to its ability to extract hydrogen at a lower potential. However, it is plagued by sluggish kinetics and noble-metal catalyst requirements. Herein, we developed nickel-iron-layered double hydroxide (NiFe-LDH) nanolayers with abundant oxygen vacancies (OV) via synergistically etching nickel foam with Fe3+ and Cl- ions, enabling the efficient conversion of urea into H2 and N2. The synthesized OV-NiFe-LDH exhibits a lower potential (1.30 vs. reversible hydrogen electrode, RHE) for achieving 10 mA cm-2 in the urea oxidation reaction (UOR), surpassing most recently reported Ni-based electrodes. OV provides favorable conductivity and a large surface area, which results in a 4.1-fold in electron transport and a 5.1-fold increase in catalyst reactive sites. Density Functional Theory (DFT) calculations indicate that OV can lower the adsorption energy of urea, and enhance the bonding strength of *CONHNH, giving rise to improved UOR. This study provides a viable path toward economical and efficient production of high-purity hydrogen.

Ferrate(VI)/percarbonate for the oxidation of micropollutants: Interactive activation and release of low-concentration hydrogen peroxide for efficient electron utilization.

A novel "ferrate/percarbonate (Fe(VI)/SPC) co-oxidation process" was used to treat ciprofloxacin (CIP) and various micropollutants (MPs), which owned better performance than mixture of Fe(VI), Na2CO3 and H2O2. The mechanism investigation found that the low-concentration H2O2 (1-2 µM) released by SPC can promote the high-valent iron intermediates (Fe(IV)/Fe(V)) of Fe(VI) to the MP oxidation, and Fe(VI) products can also activate SPC to produce hydroxyl radical (·OH). The interactive activation of Fe(VI) and SPC was realized, which retained the high selectivity of Fe(VI) to electron-rich pollutants, and also made up the oxidation of electron-deficient pollutants through •OH, improving the degradation effect of various MPs by 20-30%, and the rate constant was increased by 1 to 3 times. Moreover, non-purgeable organic carbon (NPOC) determination confirmed that â€¢OH participation reduced the NPOC value of CIP from 5.43 mg/L to 4.37 mg/L. The transformation pathway of CIP showed that Fe(VI)/SPC resulted in more hydroxylation intermediates of CIP than Fe(VI) alone. Acute toxicity assays found that the photoinhibition rate of CIP treated with Fe(VI) alone was 14.5%, while the sample treated with Fe(VI)/SPC showed no significant photoinhibition effect, which proved that the new process had good detoxification properties for CIP.

How Should We Activate Ferrate(VI)? Fe(IV) and Fe(V) Tell Different Stories about Fluoroquinolone Transformation and Toxicity Changes.

Many studies have investigated activation of ferrate (Fe(VI)) to produce reactive high-valent iron intermediates to enhance the oxidation of micropollutants. However, the differences in the risk of pollutant transformation caused by Fe(IV) and Fe(V) have not been taken seriously. In this study, Fe(VI)-alone, Fe3+/Fe(VI), and NaHCO3/Fe(VI) processes were used to oxidize fluoroquinolone antibiotics to explore the different effects of Fe(IV) and Fe(V) on product accumulation and toxicity changes. The contribution of Fe(IV) to levofloxacin degradation was 99.9% in the Fe3+/Fe(VI) process, and that of Fe(V) was 89.4% in the NaHCO3/Fe(VI) process. The cytotoxicity equivalents of levofloxacin decreased by 1.9 mg phenol/L in the Fe(IV)-dominant process while they significantly (p < 0.05) increased by 4.7 mg phenol/L in the Fe(V)-dominant process. The acute toxicity toward luminescent bacteria and the results for other fluoroquinolone antibiotics also showed that Fe(IV) reduced the toxicity and Fe(V) increased the toxicity. Density functional theory calculations showed that Fe(V) induced quinolone ring opening, which would increase the toxicity. Fe(IV) tended to oxidize the piperazine group, which reduced the toxicity. These results show the different-pollutant transformation caused by Fe(IV) and Fe(V). In future, the different risk outcomes during Fe(VI) activation should be taken seriously.

Application of the Left Lateral Decubitus Position in Laparoscopic Right Posterior Lobectomy.

OBJECTIVE: To investigate the value of the left lateral decubitus position in laparoscopic right posterior lobe tumor resection. PATIENTS AND METHODS: The clinical data of patients who underwent laparoscopic right posterior lobectomy from January 2020 to March 2023 were retrospectively collected and divided into group A (left lateral decubitus position group, n=30) and group B (conventional position group, n=35) according to different body positions. Intraoperative and postoperative data were collected and compared between the 2 groups. RESULTS: The operation time (210.43±57.56 vs. 281.97±65.89, t =5.887, P <0.05), hilar occlusion time (23.97±14.25 vs. 35.79±12.62, t =4.791, P <0.05), intraoperative blood loss (162.14±72.61 vs. 239.65±113.56, t =5.713, P <0.05), postoperative feeding time (1.13±0.36 vs. 1.57±0.67, t =3.681, P <0.05), postoperative visual analog scale score (5.16±0.89 vs. 7.42±1.31, t =3.721, P <0.05), postoperative abdominal drainage tube indwelling time (4.58±1.34 vs. 5.42±1.52, t =4.553, P <0.05), incidence rate of complications (43.33% vs. 82.86%, χ 2 =11.075, P <0.05) in group A were lower than those in group B ( P <0.05). Symptoms/side effects (32.42±3.42 vs. 27.44±3.31, t =4.331, P <0.05), and there were significant differences in social function (33.55±2.56 vs. 29.31±3.32, t =4.863, P <0.05). CONCLUSION: For right posterior lobe tumors of the liver, the left lateral decubitus position has many advantages in laparoscopic right posterior lobectomy, such as a wide field of view, simple steps, a short operation time, less bleeding, and a high postoperative quality of life. It is an effective treatment for right posterior lobe tumors of the liver and is worthy of being widely popularized.

Ferrate(VI) assists in reducing cytotoxicity and genotoxicity to mammalian cells and organic bromine formation in ozonated wastewater.

Ozonation of wastewater containing bromide (Br-) forms highly toxic organic bromine. The effectiveness of ozonation in mitigating wastewater toxicity is minimal. Simultaneous application of ozone (O3) (5 mg/L) and ferrate(VI) (Fe(VI)) (10 mg-Fe/L) reduced cytotoxicity and genotoxicity towards mammalian cells by 39.8% and 71.1% (pH 7.0), respectively, when the wastewater has low levels of Br-. This enhanced reduction in toxicity can be attributed to increased production of reactive iron species Fe(IV)/Fe(V) and reactive oxygen species (•OH) that possess higher oxidizing ability. When wastewater contains 2 mg/L Br-, ozonation increased cytotoxicity and genotoxicity by 168%-180% and 150%-155%, respectively, primarily due to the formation of organic bromine. However, O3/Fe(VI) significantly (p < 0.05) suppressed both total organic bromine (TOBr), BrO3-, as well as their associated toxicity. Electron donating capacity (EDC) measurement and precursor inference using Orbitrap ultra-high resolution mass spectrometry found that Fe(IV)/Fe(V) and •OH enhanced EDC removal from precursors present in wastewater, inhibiting electrophilic substitution and electrophilic addition reactions that lead to organic bromine formation. Additionally, HOBr quenched by self-decomposition-produced H2O2 from Fe(VI) also inhibits TOBr formation along with its associated toxicity. The adsorption of Fe(III) flocs resulting from Fe(VI) decomposition contributes only minimally to reducing toxicity. Compared to ozonation alone, integration of Fe(VI) with O3 offers improved safety for treating wastewater with varying concentrations of Br-.

Disinfection of wastewater by a complete equipment based on a novel ultraviolet light source of microwave discharge electrodeless lamp: Characteristics of bacteria inactivation, reactivation and full-scale studies.

Ultraviolet (UV) light is widely used for wastewater disinfection. Traditional electrode-excited UV lamps, such as low-pressure mercy lamps (LPUV), encounter drawbacks like electrode aging and rapid light attenuation. A novel UV source of microwave discharge electrodeless lamp (MDEL) has aroused attention, yet its disinfection performance is unclear and still far from practical application. Here, we successfully developed a complete piece of equipment based on MDELs and achieved the application for disinfection in wastewater treatment plants (WWTPs). The light emitted by an MDEL (MWUV) shared a spectrum similar to that of LPUV, with the main emission wavelength at 254 nm. The inactivation rate of Gram-negative E. coli by MWUV reached 4.5 log at an intensity of 1.6 mW/cm2 and a dose of 20 mJ/cm2. For Gram-positive B. subtilis, an MWUV dose of 50 mJ/cm2 and a light intensity of 1.2 mW/cm2 reached an inactivation rate of 3.4 log. A higher MWUV intensity led to a better disinfection effect and a lower photoreactivation rate of E. coli. When inactivated by MWUV with an intensity of 1.2 mW/cm2 and a dose of 16 mJ/cm2, the maximum photoreactivation rate and reactivation rate constant Kmax of E. coli were 0.63 % and 0.11 % h-1 respectively. Compared with the photoreactivation, the dark repair of E. coli was insignificant. The full-scale application of the MDEL equipment was conducted in two WWTPs (10,000 m3/d and 15,000 m3/d). Generally 2-3 log inactivation rates of fecal coliforms in secondary effluent were achieved within 5-6 s contact time, and the disinfected effluent met the emission standard (1000 CFU/L). This study successfully applied MDEL for disinfection in WWTPs for the first time and demonstrated that MDEL has broad application prospects.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

GK921, a transglutaminase inhibitor, strengthens the antitumor effect of cisplatin on pancreatic cancer cells by inhibiting epithelial-to-mesenchymal transition.

Pancreatic adenocarcinoma (PAAD), a common digestive malignant tumor, presents high mortality rates and limited treatment methods. Currently, chemotherapy remains the main therapy method for patients with PAAD. As a classical chemotherapy drug, cisplatin (DDP) is limited by dose-related toxicity in patients with PAAD. In this study, we demonstrated that TGM2 may be a treatment and prognosis marker in pancreatic cancer patients. Co-treatment of low dose of DDP and GK921, a transglutaminase (TGM2) inhibitor, is capable of synergistically inhibiting the PAAD cell viability and proliferation in vitro and in vivo. Based on in vitro study, GK921 inhibited the epithelial-to-mesenchymal transition (EMT) induced by TGM2 as well as aggravated cell cycle arrest and apoptosis resulted from DDP, making pancreatic cancer cells more sensible to DDP. Our results showed that GK921 increased the protein levels regarding E-cadherin as well as decreased the protein level regarding Snail2, N-cadherin, which indicated that GK921 inhibited EMT in pancreatic cancer cells. Snail2 overexpression inhibited GK921/DDP-induced cell apoptosis, as well as mitigated the GK921/DDP-caused cell death and the EMT inhibition. In vivo studies also found GK921/DDP combination can further inhibit the growth of PAAD without significantly side effects. To sum up, we showed that GK921 increased PAAD cells sensitivity to DDP via inhibiting EMT. As revealed, DDP/GK921 co-treatment could promisingly serve for treating PAAD patients.

Phototransformation of Brominated Disinfection Byproducts and Toxicity Elimination in Sunlit-Ozonated Reclaimed Water.

Ozonation is universally used during water treatment but can form hazardous brominated disinfection byproducts (Br-DBPs). While sunlight exposure is advised to reduce the risk of Br-DBPs, their phototransformation pathways remain insufficiently understood. Here, sunlight irradiation was found to reduce adsorbable organic bromine by 63%. Applying high-resolution mass spectrometry, the study investigated transformations of dissolved organic matter in sunlit-ozonated reclaimed water, revealing the number and abundance of assigned formulas decreased after irradiation. The Br-DBPs with O/C < 0.6 and MW > 400 Da were decreased or removed after irradiation, with the majority being CHOBr compounds. The peak intensity reduction ratio of CHOBr compounds correlated positively with double bound equivalent minus oxygen ratios but negatively with O/C, suggesting that photo-susceptible CHOBr compounds were highly unsaturated. Mass difference analysis revealed that the photodegradation pathways were mainly oxidation aligned with debromination. Three typical CHOBr molecular structures were resolved, and their photoproducts were proposed. Toxicity estimates indicated decreased toxicity in these photoproducts compared to their parent compounds, in line with experimentally determined values. Our proposed phototransformation pathways for Br-DBPs enhance our comprehension of their degradation and irradiation-induced toxicity reduction in reclaimed water, further illuminating their transformation under sunlight in widespread environmental scenarios.

Efficient wastewater disinfection using a novel microwave discharge electrodeless ultraviolet system with ozone at an ultra-low dose.

Microwave discharge electrodeless lamp (MDEL) is a novel ultraviolet (UV) light source. Synergistic disinfection using UV light emitted by MDEL (MWUV) coupled with ozone (O3) at an ultra-low dose was investigated. Escherichia coli and Bacillus subtilis were deactivated more effectively by MWUV/O3 than by either MWUV or O3 alone. MWUV/O3 treatment using an O3 concentration of 0.4 mg/L gave an E. coli inactivation rate of 5.52 log. The photoreactivation degree and rate of E. coli were lower after inactivation by MWUV/O3 treatment than after MWUV treatment alone. The maximum photoreactivation rates after the MWUV/O3 and MWUV treatments were 2.90% and 16.08%, respectively. MWUV/O3 disinfection also inhibited dark resurrection of E. coli and gave a maximum dark resurrection rate of 0.0036%. Electron paramagnetic resonance spectroscopy indicated that more hydroxyl radicals were generated during MWUV/O3 treatment. Scanning electron microscopy and laser confocal scanning microscopy observations indicated that O3 played a key role in breaking down the cell structure. MWUV/O3 treatment gave a good disinfection effect on fecal coliform bacteria in actual domestic wastewater. The results indicated that inactivation of bacteria can be more effectively achieved by MWUV treatment with O3.

Associations of 10 dietary habits with breast cancer: a Mendelian randomization study.

Introduction: Epidemiological studies have revealed a link between dietary habits and the breast cancer risk. The causality of the association between food consumption and breast cancer requires further investigation. Methods: Using Mendelian randomization, we assessed the causal effects of 10 dietary habits on the risks of breast cancer and its subtypes (estrogen receptor [ER] + and ER- breast cancer). We obtained dietary pattern data in 2018 (number of single-nucleotide polymorphisms [SNPs] = 9,851,867) and breast cancer data in 2017 (number of SNPs = 10,680,257) from IEU OpenGWAS. Rigorous sensitivity analyses were conducted to ensure that the study results were credible and robust. Results: We identified that genetic predisposition to higher dried fruit intake was linked to a reduced risk of overall breast cancer (inverse variance-weighted [IVW] odds ratio [OR] = 0.55; 95% confidence interval [CI]: 0.43-0.70; p = 1.75 × 10-6), ER+ breast cancer (IVW OR = 0.62; 95% CI: 0.47-0.82; p = 8.96 × 10-4) and ER- breast cancer (IVW OR = 0.48; 95% CI: 0.34-0.68; p = 3.18 × 10-5), whereas genetic predisposition to more oily fish intake was linked to a lower risk of ER+ breast cancer (IVW OR = 0.73; 95% CI: 0.53-0.99; p = 0.04). Discussion: Our findings suggest that a genetic predisposition for dried fruit and oily fish consumption may be protective against breast cancer; however, further investigation is required.

A Homochiral Fulgide Organic Ferroelectric Crystal with Photoinduced Molecular Orbital Breaking.

Thermally triggered spatial symmetry breaking in traditional ferroelectrics has been extensively studied for manipulation of the ferroelectricity. However, photoinduced molecular orbital breaking, which is promising for optical control of ferroelectric polarization, has been rarely explored. Herein, for the first time, we synthesized a homochiral fulgide organic ferroelectric crystal (E)-(R)-3-methyl-3-cyclohexylidene-4-(diphenylmethylene)dihydro-2,5-furandione (1), which exhibits both ferroelectricity and photoisomerization. Significantly, 1 shows a photoinduced reversible change in its molecular orbitals from the 3 π molecular orbitals in the open-ring isomer to 2 π and 1 σ molecular orbitals in the closed-ring isomer, which enables reversible ferroelectric domain switching by optical manipulation. To our knowledge, this is the first report revealing the manipulation of ferroelectric polarization in homochiral ferroelectric crystal by photoinduced breaking of molecular orbitals. This finding sheds light on the exploration of molecular orbital breaking in ferroelectrics for optical manipulation of ferroelectricity.

Causal pathways linking polycystic ovary syndrome to distinct breast cancer subtypes through mediator factors: a multivariable mendelian randomization analysis.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovarian cysts, high androgen levels, and irregular menstruation. The causality between PCOS and breast cancer (BC) has been widely discussed as they share a significant intersection in clinical manifestations. Previous epidemiological studies have not provided consistent conclusions in association between PCOS and BC, while mendelian randomization (MR) analyses have confirmed the causality between PCOS and estrogen receptor-positive breast cancer (ER + BC), but among a series of clinical manifestations resulting from PCOS, which related traits mediate the causal effect remains unknown. In this study, we conducted multivariable mendelian randomization (MVMR) analysis to explore the potential mediator variables in the mechanism linking PCOS to distinct subtypes of BC, and calculated the mediating effects proportion. We analyzed 13 PCOS-related traits and found that age at menopause may mediate PCOS-induced ER + BC (with -4.82% proportion) with a weak protective effect through the repair of DNA double-strand breaks by homologous recombination. This study helps to better comprehend the shared mechanisms contributing to the development of both PCOS and BC, and to screen high-risk populations for BC and take appropriate preventive measures.

Stiffened tumor microenvironment enhances perineural invasion in breast cancer via integrin signaling.

BACKGROUND: Accumulating studies have shown that tumors are regulated by nerves, and there is abundant nerve infiltration in the tumor microenvironment. Many solid tumors including breast cancer (BRCA) have different degrees of perineural invasion (PNI), which is closely related to the tumor occurrence and progression. However, the regulatory mechanism of PNI in BRCA remains largely unexplored. METHODS: PNI-related molecular events are analyzed by the RNAseq data of BRCA samples deposited in The Cancer Genome Atlas (TCGA) database. Extracellular matrix (ECM) components within the tumor microenvironment are analyzed by immunohistochemical staining of α-SMA, Sirius red staining, and Masson trichrome staining. Soft and stiff matrix gels, living cell imaging, and dorsal root ganglion (DRG) coculture assay are used to monitor cancer cell invasiveness towards nerves. Western blotting, qRT-PCR, enzyme-linked immunosorbent assay combined with neutralizing antibody and small molecular inhibitors are employed to decode molecular mechanisms. RESULTS: Comparative analysis that the ECM was significantly associated with PNI status in the TCGA cohort. BRCA samples with higher α-SMA activity, fibrillar collagen, and collagen content had higher frequency of PNI. Compared with soft matrix, BRCA cells cultured in stiff matrix not only displayed higher cell invasiveness to DRG neurons but also had significant neurotrophic effects. Mechanistically, integrin ß1 was identified as a functional receptor to the influence of stiff matrix on BRCA cells. Moreover, stiffened matrix-induced activation of integrin ß1 transduces FAK-YAP signal cascade, which enhances cancer invasiveness and the neurotrophic effects. In clinical setting, PNI-positive BRCA samples had higher expression of ITGB1, phosphorylated FAK, YAP, and NGF compared with PNI-negative BRCA samples. CONCLUSIONS: Our findings suggest that stiff matrix induces expression of pro-metastatic and neurotrophic genes through integrin ß1-FAK-YAP signals, which finally facilitates PNI in BRCA. Thus, our study provides a new mechanism for PNI in BRCA and highlights nerve-based tumor treatment strategies.

pH-dependent bisphenol A transformation and iodine disinfection byproduct generation by peracetic acid: Kinetic and mechanistic explorations.

Peracetic acid (PAA) is regarded as an environmentally friendly oxidant because of its low formation of toxic byproducts. However, this study revealed the potential risk of generating disinfection byproducts (DBPs) when treating iodine-containing wastewater with PAA. The transformation efficiency of bisphenol A (BPA), a commonly detected phenolic contaminant and a surrogate for phenolic moieties in dissolved organic matter, by PAA increased rapidly in the presence of I-, which was primarily attributed to the formation of active iodine (HOI/I2) in the system. Kinetic model simulations demonstrated that the second-order rate constant between PAA and HOI was 54.0 M-1 s-1 at pH 7.0, which was lower than the generation rate of HOI via the reaction between PAA and I-. Therefore, HOI can combine with BPA to produce iodine disinfection byproducts (I-DBPs). The transformation of BPA and the generation of I-DBPs in the I-/PAA system were highly pH-dependent. Specifically, acidic conditions were more favorable for BPA degradation because of the higher reaction rates of BPA and HOI. More iodinated aromatic products were detected after 5 min of the reaction under acidic and neutral conditions, resulting in higher toxicity towards E. coli. After 12 h of the reaction, more adsorbable organic iodine (AOI) was generated at alkaline conditions because HOI was not able to efficiency transform to IO3-. The presence of H2O2 in the PAA solution played a role in the reaction with HOI, particularly under alkaline conditions. This study significantly advances the understanding of the role of I- in BPA oxidation by PAA and provides a warning to further evaluate the potential environmental risk during the treatment of iodine-bearing wastewater with PAA.