Adaptive resistance of tumor cells to anti-vascular endothelial growth factor therapy: A reversible phenomenon.

Vascular endothelial growth factor (VEGF) inhibition is an essential targeted strategy for malignant tumors, but its efficacy is severely constrained by drug resistance. The traditional view holds that the target of VEGF inhibition is endothelial cells, and thus compensatory angiogenesis is considered the main mechanism of drug resistance. In this study, we found that tumor cells themselves could develop acquired resistance to VEGF therapy, indicating an independent resistance mechanism apart from angiogenesis. Notably, this acquired resistance was temporary, disappearing completely four days after discontinuing exposure to the drug in vitro. Our findings suggest that tumor cells may also be targets of VEGF inhibition, and their response to treatment should not be overlooked in contributing to drug resistance.

Impacts of Perioperative Comprehensive Nursing Intervention on Postoperative Urinary Incontinence and Quality of Life of Patients Undergoing Laparoscopic Radical Prostatectomy.

To evaluate the impact of perioperative comprehensive nursing intervention on postoperative urinary incontinence, various aspects of patient well-being were assessed. The comprehensive group, that received the nursing intervention, demonstrated significant improvements in self-care skills, health knowledge level, self-care responsibility, and self-concept compared to the standard group. The findings indicate that perioperative comprehensive nursing intervention has a remarkable effect on patients undergoing laparoscopic radical prostatectomy. This nursing intervention not only effectively improves postoperative urinary incontinence and alleviates negative emotions, such as anxiety and depression. Therefore, the implementation of this nursing intervention model is highly recommended for clinical practice and wider application.

Lineage Tracing and Single-Nucleus Multiomics Reveal Novel Features of Adaptive and Maladaptive Repair after Acute Kidney Injury.

SIGNIFICANCE STATEMENT: Understanding the mechanisms underlying adaptive and maladaptive renal repair after AKI and their long-term consequences is critical to kidney health. The authors used lineage tracing of cycling cells and single-nucleus multiomics (profiling transcriptome and chromatin accessibility) after AKI. They demonstrated that AKI triggers a cell-cycle response in most epithelial and nonepithelial kidney cell types. They also showed that maladaptive proinflammatory proximal tubule cells (PTCs) persist until 6 months post-AKI, although they decreased in abundance over time, in part, through cell death. Single-nucleus multiomics of lineage-traced cells revealed regulatory features of adaptive and maladaptive repair. These included activation of cell state-specific transcription factors and cis-regulatory elements, and effects in PTCs even after adaptive repair, weeks after the injury event. BACKGROUND: AKI triggers a proliferative response as part of an intrinsic cellular repair program, which can lead to adaptive renal repair, restoring kidney structure and function, or maladaptive repair with the persistence of injured proximal tubule cells (PTCs) and an altered kidney structure. However, the cellular and molecular understanding of these repair programs is limited. METHODS: To examine chromatin and transcriptional responses in the same cell upon ischemia-reperfusion injury (IRI), we combined genetic fate mapping of cycling ( Ki67+ ) cells labeled early after IRI with single-nucleus multiomics-profiling transcriptome and chromatin accessibility in the same nucleus-and generated a dataset of 83,315 nuclei. RESULTS: AKI triggered a broad cell cycle response preceded by cell type-specific and global transcriptional changes in the nephron, the collecting and vascular systems, and stromal and immune cell types. We observed a heterogeneous population of maladaptive PTCs throughout proximal tubule segments 6 months post-AKI, with a marked loss of maladaptive cells from 4 weeks to 6 months. Gene expression and chromatin accessibility profiling in the same nuclei highlighted differences between adaptive and maladaptive PTCs in the activity of cis-regulatory elements and transcription factors, accompanied by corresponding changes in target gene expression. Adaptive repair was associated with reduced expression of genes encoding transmembrane transport proteins essential to kidney function. CONCLUSIONS: Analysis of genome organization and gene activity with single-cell resolution using lineage tracing and single-nucleus multiomics offers new insight into the regulation of renal injury repair. Weeks to months after mild-to-moderate IRI, maladaptive PTCs persist with an aberrant epigenetic landscape, and PTCs exhibit an altered transcriptional profile even following adaptive repair.

Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies.

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs. To examine their functional significance, we deleted 'hotspot' enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis.

Renoprotective and Immunomodulatory Effects of GDF15 following AKI Invoked by Ischemia-Reperfusion Injury.

BACKGROUND: Gdf15 encodes a TGF-ß superfamily member that is rapidly activated in response to stress in multiple organ systems, including the kidney. However, there has been a lack of information about Gdf15 activity and effects in normal kidney and in AKI. METHODS: We used genome editing to generate a Gdf15nuGFP-CE mouse line, removing Gdf15 at the targeted allele, and enabling direct visualization and genetic modification of Gdf15-expressing cells. We extensively mapped Gdf15 expression in the normal kidney and following bilateral ischemia-reperfusion injury, and quantified and compared renal responses to ischemia-reperfusion injury in the presence and absence of GDF15. In addition, we analyzed single nucleotide polymorphism association data for GDF15 for associations with patient kidney transplant outcomes. RESULTS: Gdf15 is normally expressed within aquaporin 1-positive cells of the S3 segment of the proximal tubule, aquaporin 1-negative cells of the thin descending limb of the loop of Henle, and principal cells of the collecting system. Gdf15 is rapidly upregulated within a few hours of bilateral ischemia-reperfusion injury at these sites and new sites of proximal tubule injury. Deficiency of Gdf15 exacerbated acute tubular injury and enhanced inflammatory responses. Analysis of clinical transplantation data linked low circulating levels of GDF15 to an increased incidence of biopsy-proven acute rejection. CONCLUSIONS: Gdf15 contributes to an early acting, renoprotective injury response, modifying immune cell actions. The data support further investigation in clinical model systems of the potential benefit from GDF15 administration in situations in which some level of tubular injury is inevitable, such as following a kidney transplant.

A novel distal convoluted tubule-specific Cre-recombinase driven by the NaCl cotransporter gene.

Cre-lox technology has revolutionized research in renal physiology by allowing site-specific genetic recombination in individual nephron segments. The distal convoluted tubule (DCT), consisting of distinct early (DCT1) and late (DCT2) segments, plays a central role in Na+ and K+ homeostasis. The only established Cre line targeting the DCT is Pvalb-Cre, which is limited by noninducibility, activity along DCT1 only, and activity in neurons. Here, we report the characterization of the first Cre line specific to the entire DCT. CRISPR/Cas9 targeting was used to introduce a tamoxifen-inducible IRES-Cre-ERT2 cassette downstream of the coding region of the Slc12a3 gene encoding the NaCl cotransporter (NCC). The resulting Slc12a3-Cre-ERT2 mice were crossed with R26R-YFP reporter mice, which revealed minimal leakiness with 6.3% of NCC-positive cells expressing yellow fluorescent protein (YFP) in the absence of tamoxifen. After tamoxifen injection, YFP expression was observed in 91.2% of NCC-positive cells and only in NCC-positive cells, revealing high recombination efficiency and DCT specificity. Crossing to R26R-TdTomato mice revealed higher leakiness (64.5%), suggesting differential sensitivity of the floxed site. Western blot analysis revealed no differences in abundances of total NCC or the active phosphorylated form of NCC in Slc12a3-Cre-ERT2 mice of either sex compared with controls. Plasma K+ and Mg2+ concentrations and thiazide-sensitive Na+ and K+ excretion did not differ in Slc12a3-Cre-ERT2 mice compared with controls when sex matched. These data suggest genetic modification had no obvious effect on NCC function. Slc12a3-Cre-ERT2 mice are the first line generated demonstrating inducible Cre recombinase activity along the entire DCT and will be a useful tool to study DCT function.

A New Family of Disorder-Free Rare-Earth-Based Kagome Lattice Magnets: Structure and Magnetic Characterizations of RE3BWO9 (RE = Pr, Nd, Gd-Ho) Boratotungstates.

Exploration of rare-earth (RE)-based Kagomé lattice magnets with spin-orbital entangled jeff = 1/2 moments will provide a new platform for investigating the exotic magnetic phases. Here, we report a new family of RE3BWO9 (RE = Pr,Nd,Gd-Ho) boratotungstates with magnetic RE3+ ions arranged on Kagomé lattice and perform its structure and magnetic characterizations. These serial compounds crystallize in a hexagonal coordinated structure with space group P63 (no. 173), where magnetic RE3+ ions have distorted Kagomé lattice connections within the ab plane and stacked in an AB-type fashion along the c axis. The interlayer RE-RE separation is comparable with that of the intralayer distance, forming 3-dimensional (3D) exchange coupled magnetic framework of RE3+ ions. The magnetic susceptibility data of RE3BWO9 (RE = Pr, Nd, Gd-Ho) reveal dominant antiferromagnetic interactions between magnetic RE3+ ions, but without visible magnetic ordering down to 2 K. The magnetization analyses for different RE3+ ions show diverse anisotropic behaviors, making RE3BWO9 as an appealing Kagomé-lattice antiferromagnet to explore exotic magnetic phases.

Gelatin sponge functionalized with gold/silver clusters for antibacterial application.

Pathogenic bacterial infection, especially in the wound, may threaten human health. Developing new antibacterial materials for wound healing is still urgent. Metal nanoclusters have been explored as a novel antibacterial agent. Herein, biomolecule gelatin was chosen as a substrate and functionalized with gold/silver clusters for bacterial killing. Through a simple amidation reaction, gold/silver clusters were successfully conjugated in a gelatin substrate to obtain a Au/Ag@gelatin sponge. The presence of gold/silver clusters modified the porous structure of the gelatin. Thus, the water absorption and water retention of the Au/Ag@gelatin sponge were enhanced. More importantly, the gold/silver clusters show aggregation-enhanced emission and strong reactive oxygen generation, that endow the Au/Ag@gelatin sponge with a good antibacterial property. The good physical performance and favorable bactericidal activity of the Au/Ag@gelatin sponge suggest its potential for application as a wound dressing.

Combined application of soluble organic and chemical fertilizers in drip fertigation improves nitrogen use efficiency and enhances tomato yield and quality.

BACKGROUND: Sustainable greenhouse tomato production requires optimal fertilizer management to achieve the double-win strategy of producing high yields and maximizing profits with less environmental pollution. The objective of this study was to seek an optimal fertilization strategy maintaining high productivity of greenhouse tomato, improving nitrogen use efficiency and reducing nitrate leaching risk. RESULTS: The combined application of soluble organic and chemical fertilizers for topdressing (SOSC) not only produced more fruit yield (75.18 Mg ha-1 ) and plant dry matter (10 449.12 kg ha-1 ), but also enhanced plant nutrients uptake, nitrogen recovery efficiency (39.22%), nitrogen agronomic efficiency (176.78 kg kg-1 ), soluble solids, vitamin C and lycopene content in tomato fruits compared with the other treatments, that is chicken manures for basal application and chemical fertilizer for topdressing (CC), soluble organic fertilizer for topdressing (SO) and soluble chemical fertilizer for topdressing (SC). In terms of soil nutrients residue, SOSC had no obvious NO3 - -N accumulation area in the 0-60 cm soil layer, unlike large accumulation in the soil layer below 30 cm in SO and SC. CONCLUSION: The combined application of soluble organic and chemical fertilizers is highly recommended to sustain fruit yield, improve nitrogen use efficiency and reduce soil degradation risks in commercial greenhouse tomato production.

Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning.

The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal-distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, we identified a novel nephron subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature nephron. Significant conservation was observed between human and mouse patterning. We also determined the time at which markers for mature nephron cell types first emerge-critical data for the renal organoid field. These findings have conceptual implications for the evolutionary processes driving the diversity of mammalian organ systems. Furthermore, these findings provide practical insights beyond those gained with mouse and rat models that will guide in vitro efforts to harness the developmental programs necessary to build human kidney structures.

Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney.

Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1, were readily detected within SIX2+ NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2+ NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2, are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs.

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.

Optical vector network analyzer based on double-sideband modulation.

We report an optical vector network analyzer (OVNA) based on double-sideband (DSB) modulation using a dual-parallel Mach-Zehnder modulator. The device under test (DUT) is measured twice with different modulation schemes. By post-processing the measurement results, the response of the DUT can be obtained accurately. Since DSB modulation is used in our approach, the measurement range is doubled compared with conventional single-sideband (SSB) modulation-based OVNA. Moreover, the measurement accuracy is improved by eliminating the even-order sidebands. The key advantage of the proposed scheme is that the measurement of a DUT with bandpass response can also be simply realized, which is a big challenge for the SSB-based OVNA. The proposed method is theoretically and experimentally demonstrated.

Electrochemical detection of C-reactive protein using Copper nanoparticles and hybridization chain reaction amplifying signal.

In this study, a sandwich-type electrochemical immunosensor for the detection of C-reactive protein (CRP) is described. In design, Copper nanoparticles (Cu NPs) were used for signal tag and hybridization chain reaction (HCR)amplified output signal. The immunosensor fabrication involved three steps: (i) primary antibodies (Ab1) were immobilized on the surface of gold nanoparticles (Au NPs); (ii) the sandwich-type structure formation contained "primary antibodies-antigen-secondary antibodies conjugated with primer (Ab2-S0)"; and (iii) long DNA concatemers intercalating amounts of Cu NPs was linked to the sandwich-type structure via hybridization reaction. Differential pulse voltammetry (DPV) was used to record the response signal of the immunosensor in phosphate-buffered saline (PBS). Under optimal conditions, the anodic peak currents of Cu NPs at the peak potential of about 0.08V(VS.SCE) were linear with the logarithm of CRP concentration in the range of 1.0 fg mL-1 to 100 ng mL-1 with a detection limit of 0.33 fg mL-1 (at signal/noise [S/N] = 3). In addition, the practical application of immunosensor was evaluated by analyzing CRP in real human serum samples, the recoveries obtained were within 95.3%-103.8%, indicating the immunosensor possessed potential application ability for practical disease diagnosis.

Collecting duct-derived cells display mesenchymal stem cell properties and retain selective in vitro and in vivo epithelial capacity.

We previously described a mesenchymal stem cell (MSC)-like population within the adult mouse kidney that displays long-term colony-forming efficiency, clonogenicity, immunosuppression, and panmesodermal potential. Although phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent protein (GFP) mice identified the collecting duct as a source of kidney MSC-like cells, with these cells undergoing an epithelial-to-mesenchymal transition to form clonogenic, long-term, self-renewing MSC-like cells. Notably, after extensive passage, kidney MSC-like cells selectively integrated into the aquaporin 2-positive medullary collecting duct when microinjected into the kidneys of neonatal mice. No epithelial integration was observed after injection of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial structures in vitro and in vivo, and conditioned media from these cells supported epithelial repair in vitro. To investigate the origin of kidney MSC-like cells, we further examined Hoxb7(+) fractions within the kidney across postnatal development, identifying a neonatal interstitial GFP(lo) (Hoxb7(lo)) population displaying an expression profile intermediate between epithelium and interstitium. Temporal analyses with Wnt4(GCE/+):R26(tdTomato/+) mice revealed evidence for the intercalation of a Wnt4-expressing interstitial population into the neonatal collecting duct, suggesting that such intercalation may represent a normal developmental mechanism giving rise to a distinct collecting duct subpopulation. These results extend previous observations of papillary stem cell activity and collecting duct plasticity and imply a role for such cells in collecting duct formation and, possibly, repair.

Identification of molecular compartments and genetic circuitry in the developing mammalian kidney.

Lengthy developmental programs generate cell diversity within an organotypic framework, enabling the later physiological actions of each organ system. Cell identity, cell diversity and cell function are determined by cell type-specific transcriptional programs; consequently, transcriptional regulatory factors are useful markers of emerging cellular complexity, and their expression patterns provide insights into the regulatory mechanisms at play. We performed a comprehensive genome-scale in situ expression screen of 921 transcriptional regulators in the developing mammalian urogenital system. Focusing on the kidney, analysis of regional-specific expression patterns identified novel markers and cell types associated with development and patterning of the urinary system. Furthermore, promoter analysis of synexpressed genes predicts transcriptional control mechanisms that regulate cell differentiation. The annotated informational resource (www.gudmap.org) will facilitate functional analysis of the mammalian kidney and provides useful information for the generation of novel genetic tools to manipulate emerging cell populations.

Horseradish peroxidase functionalized gold nanorods as a label for sensitive electrochemical detection of alpha-fetoprotein antigen.

In this study, a novel tracer, horseradish peroxidase (HRP) functionalized gold nanorods (Au NRs) nanocomposites (HRP-Au NRs), was designed to label the signal antibodies for sensitive electrochemical measurement of alpha-fetoprotein (AFP). The preparation of HRP-Au NRs nanocomposites and the labeling of secondary antibody (Ab2) were performed by one-pot assembly of HRP and Ab2 on the surface of Au NRs. The immunosensor was fabricated by assembling carbon nanotubes (CNTs), Au NRs, and capture antibodies (Ab1) on the glassy carbon electrode. In the presence of AFP antigen, the labels were captured on the surface of the Au NRs/CNTs via specific recognition of antigen-antibody, resulting in the signal intensity being clearly increased. Differential pulse voltammetry (DPV) was employed to record the response signal of the immunosensor in phosphate-buffered saline (PBS) containing hydrogen peroxide (H2O2) and 3,3',5,5'-tetramethylbenzidine (TMB). Under optimal conditions, the signal intensity was linearly related to the concentration of AFP in the range of 0.1-100 ng ml(-1), and the limit of detection was 30 pg ml(-1) (at signal/noise [S/N] = 3). Furthermore, the immunoassay method was evaluated using human serum samples, and the recovery obtained was within 99.0 and 102.7%, indicating that the immunosensor has potential clinical applications.

Neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways.

Clara cells of mammalian airways have multiple functions and are morphologically heterogeneous. Although Notch signaling is essential for the development of these cells, it is unclear how Notch influences Clara cell specification and if diversity is established among Clara cell precursors. Here we identify expression of the secretoglobin Scgb3a2 and Notch activation as early events in a program of secretory cell fate determination in developing murine airways. We show that Scgb3a2 expression in vivo is Notch-dependent at early stages and ectopically induced by constitutive Notch1 activation, and also that in vitro Notch signaling together with the pan-airway transcription factor Ttf1 (Nkx2.1) synergistically regulate secretoglobin gene transcription. Furthermore, we identified a subpopulation of secretory precursors juxtaposed to presumptive neuroepithelial bodies (NEBs), distinguished by their strong Scgb3a2 and uroplakin 3a (Upk3a) signals and reduced Ccsp (Scgb1a1) expression. Genetic ablation of Ascl1 prevented NEB formation and selectively interfered with the formation of this subpopulation of cells. Lineage labeling of Upk3a-expressing cells during development showed that these cells remain largely uncommitted during embryonic development and contribute to Clara and ciliated cells in the adult lung. Together, our findings suggest a role for Notch in the induction of a Clara cell-specific program of gene expression, and reveals that the NEB microenvironment in the developing airways is a niche for a distinct subset of Clara-like precursors.

Multichannel optical filters with an ultranarrow bandwidth based on sampled Brillouin dynamic gratings.

We first propose a multichannel optical filter with an ultra-narrow 3-dB bandwidth based on sampled Brillouin dynamic gratings (SBDGs). The multichannel optical filter is generated when an optical pulse interfaces with an optical pulse train based on an ordinary stimulated Brillouin scattering (SBS) process in a birefringent optical fiber. Multichannel optical filter based on SBDG is generated with a 3-dB bandwidth from 12.5 MHz to 1 GHz. In addition, a linearly chirped SBDG is proposed to generate multichannel dispersion compensator with a 3-dB bandwidth of 300 MHz and an extremely high dispersion value of 432 ns/nm. The proposed multichannel optical filters have important potential applications in the optical filtering, multichannel dispersion compensation and optical signal processing.

The association between prenatal exposure to bisphenol A and offspring obesity: A systematic review.

In recent years, the global prevalence of childhood overweight and obesity has surged. Bisphenol A (BPA), prevalent in the manufacture of polycarbonate plastics and epoxy resins, is associated with this escalating obesity pattern. Both early life stages and pregnancy emerge as pivotal windows of vulnerability. This review systematically evaluates human studies to clarify the nexus between prenatal BPA exposure and offspring obesity. Our extensive literature search covered databases like PubMed, Web of Science, Cochrane Library, Embase, and Scopus, encompassing articles from their inception until July 2023. We utilized the Newcastle-Ottawa Scale (NOS) to evaluate the methodological rigor of the included studies, the Oxford Center for Evidence-Based Medicine Levels of Evidence Working Group (OCEBM) table to determine the level of the evidence, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidelines to evaluate the certainty of the evidence with statistical significance. We centered on primary studies investigating the link between urinary BPA levels during pregnancy and offspring obesity. Our analysis included thirteen studies, with participant counts ranging from 173 to 1124 mother-child dyads. Among them, eight studies conclusively linked prenatal BPA exposure to increased obesity in offspring. Evaluation metrics for the effect of prenatal BPA on offspring obesity comprised BMI z-score, waist circumference, overweight/obesity classification, aggregate skinfold thickness, body fat percentage, and more. Present findings indicate that prenatal BPA exposure amplifies offspring obesity risk, with potential effect variations by age and gender. Therefore, further research is needed to explore the causal link between prenatal BPA exposure and obesity at different developmental stages and genders, and to elucidate the underlying mechanisms.