Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

CTD Sensors for Ocean Investigation Including State of Art and Commercially Available.

Over 70% of the earth's surface is covered by oceans; globally, oceans provides a huge source of wealth to humans. In the literature, several sensors have been developed to investigate oceans. Electrical conductivity temperature depth (CTD) sensors were used frequently and extensively. Long-term accurate CTD data is important for the study and utilization of oceans, e.g., for weather forecasting, ecological evolution, fishery, and shipping. Several kinds of CTD sensors based on electrics, optical, acoustic wave and radio waves have been developed. CTD sensors are often utilized by measuring electrical signals. The latest progress of CTD sensors will be presented in order of performance. The principles, structure, materials and properties of many CTD sensors were discussed in detail. The commercially available CTD sensors were involved and their respective performances were compared. Some possible development directions of CTD sensors for ocean investigation are proposed.

Leaf transcriptomic response mediated by cold stress in two maize inbred lines with contrasting tolerance levels.

Maize (Zea mays L.) is a thermophilic plant and a minor drop in temperature can prolong the maturity period. Plants respond to cold stress through structural and functional modification in cell membranes as well as changes in the photosynthesis and energy metabolism. In order to understand the molecular mechanisms underlying cold tolerance and adaptation, we employed leaf transcriptome sequencing together with leaf microstructure and relative electrical conductivity measurements in two maize inbred lines, having different cold stress tolerance potentials. The leaf physiological and transcriptomic responses of maize seedlings were studied after growing both inbred lines at 5 °C for 0, 12 and 24 h. Differentially expressed genes were enriched in photosynthesis antenna proteins, MAPK signaling pathway, plant hormone signal transduction, circadian rhythm, secondary metabolites related pathways, ribosome, and proteasome. The seedlings of both genotypes employed common stress responsive pathways to respond to cold stress. However, the cold tolerant line B144 protected its photosystem II from photooxidation by upregulating D1 proteins. The sensitive line Q319 was unable to close its stomata. Collectively, B144 exhibited a cold tolerance owing to its ability to mediate changes in stomata opening as well as protecting photosystem. These results increase our understanding on the cold stress tolerance in maize seedlings and propose multiple key regulators of stress responses such as modifications in photosystem II, stomata guard cell opening and closing, changes in secondary metabolite biosynthesis, and circadian rhythm. This study also presents the signal transduction related changes in MAPK and phytohormone signaling pathways in response to cold stress during seedling stage of maize.

Black Phosphorus Mid-Infrared Light-Emitting Diodes Integrated with Silicon Photonic Waveguides.

Light-emitting diodes (LEDs) based on III-V/II-VI materials have delivered a compelling performance in the mid-infrared (mid-IR) region, which enabled wide-ranging applications in sensing, including environmental monitoring, defense, and medical diagnostics. Continued efforts are underway to realize on-chip sensors via heterogeneous integration of mid-IR emitters on a silicon photonic chip, but the uptake of such an approach is limited by the high costs and interfacial strains, associated with the processes of heterogeneous integrations. Here, the black phosphorus (BP)-based van der Waals (vdW) heterostructures are exploited as room-temperature LEDs. The demonstrated devices emit linearly polarized light, and the spectra cover the technologically important mid-IR atmospheric window. Additionally, the BP LEDs exhibit fast modulation speed and exceptional operation stability. The measured peak extrinsic quantum efficiency is comparable to the III-V/II-VI mid-IR LEDs. By leveraging the integrability of vdW heterostructures, we further demonstrate a silicon photonic waveguide-integrated BP LED.

A Deep Learning Model for Fault Diagnosis with a Deep Neural Network and Feature Fusion on Multi-Channel Sensory Signals.

Collecting multi-channel sensory signals is a feasible way to enhance performance in the diagnosis of mechanical equipment. In this article, a deep learning method combined with feature fusion on multi-channel sensory signals is proposed. First, a deep neural network (DNN) made up of auto-encoders is adopted to adaptively learn representative features from sensory signal and approximate non-linear relation between symptoms and fault modes. Then, Locality Preserving Projection (LPP) is utilized in the fusion of features extracted from multi-channel sensory signals. Finally, a novel diagnostic model based on multiple DNNs (MDNNs) and softmax is constructed with the input of fused deep features. The proposed method is verified in intelligent failure recognition for automobile final drive to evaluate its performance. A set of contrastive analyses of several intelligent models based on the Back-Propagation Neural Network (BPNN), Support Vector Machine (SVM) and the proposed deep architecture with single sensory signal and multi-channel sensory signals is implemented. The proposed deep architecture of feature extraction and feature fusion on multi-channel sensory signals can effectively recognize the fault patterns of final drive with the best diagnostic accuracy of 95.84%. The results confirm that the proposed method is more robust and effective than other comparative methods in the contrastive experiments.

Association of klotho gene polymorphism and the regulation of calcium-phosphate metabolism disorders in patients with end-stage renal disease.

BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects. RESULTS: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders. CONCLUSION: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.

Ultrathin van der Waals Metalenses.

Ultrathin and flat optical lenses are essential for modern optical imaging, spectroscopy, and energy harvesting. Dielectric metasurfaces comprising nanoscale quasi-periodic resonator arrays are promising for such applications, as they can tailor the phase, amplitude, and polarization of light at subwavelength resolution, enabling multifunctional optical elements. To achieve 2π phase coverage, however, most dielectric metalenses need a thickness comparable to the wavelength, requiring the fabrication of high-aspect-ratio scattering elements. We report ultrathin dielectric metalenses made of van der Waals (vdW) materials, leveraging their high refractive indices and the incomplete phase design approach to achieve device thicknesses down to ∼λ/10, operating at infrared and visible wavelengths. These materials have generated strong interest in recent years due to their advantageous optoelectronic properties. Using vdW metalenses, we demonstrate near-diffraction-limited focusing and imaging and exploit their layered nature to transfer the fabricated metalenses onto flexible substrates to show strain-induced tunable focusing. Our work enables further downscaling of optical elements and opportunities for the integration of metasurface optics in ultraminiature optoelectronic systems.

Significance of M2 macrophage in tubulointerstitial disease secondary to primary Sjogren's disease.

OBJECTIVE: M2 Macrophages could improve tubulointerstitial disease in animal models. HIF-1αpromotes macrophage polarization and is involved in tubular injury. The study aims to observe the clinicopathologic significance of M2 macrophage and HIF-1α in tubulointerstitial injury secondary to primary Sjogren's disease. METHODS: Renal tissue samples from patients with tubulointerstitial disease secondary to primary Sjogren's disease (SS, n = 10), chronic tubulointerstitial nephritis secondary to drug (CIN, n = 8) were included in this study. The expression of CD163, CD68 and HIF-1α were examined by immunohistochemistry or immunofluorescence. RESULTS: (1) Renal involvement was the first manifestation in seven of ten (7/10) patients with pSS, including proteinuria, renal dysfunction, renal tubular acidosis and multiple renal stone; and two patient had intractable hypokalemia. (2) There were numerous CD163- positive cells and CD68- positive cells infiltration in tubulointerstitial injury of pSS, especially in patients with hypokalemia. CD163 positive cells and HIF-1αwere mainly expressed in acute tubulointerstitial injury of pSS, which positively correlated to N-acetyl-ß-D-glucosaminidase and ß2-microglobulin. (3) Compared with CIN, patients with pSS had higher serum globulin level, erythrocyte sedimentation rate (ESR) and lower urinary osmotic pressure. (4) During follow-up of one year, six patients with pSS and acute tubular injury acquired improved renal function on therapy of steroid and total glucosides of peony. The remaining four patients with pSS had stable renal function. CONCLUSION: M2 macrophages are involved in acute tubular injury in patients with primary Sjogren's disease. Early intervention can improve renal function of tubulointerstitial injury secondary to primary Sjogren's disease.

Nanocavity Integrated van der Waals Heterostructure Light-Emitting Tunneling Diode.

Developing a nanoscale, integrable, and electrically pumped single mode light source is an essential step toward on-chip optical information technologies and sensors. Here, we demonstrate nanocavity enhanced electroluminescence in van der Waals heterostructures (vdWhs) at room temperature. The vertically assembled light-emitting device uses graphene/boron nitride as top and bottom tunneling contacts and monolayer WSe2 as an active light emitter. By integrating a photonic crystal cavity on top of the vdWh, we observe the electroluminescence is locally enhanced (>4 times) by the nanocavity. The emission at the cavity resonance is single mode and highly linearly polarized (84%) along the cavity mode. By applying voltage pulses, we demonstrate direct modulation of this single mode electroluminescence at a speed of ∼1 MHz, which is faster than most of the planar optoelectronics based on transition metal chalcogenides (TMDCs). Our work shows that cavity integrated vdWhs present a promising nanoscale optoelectronic platform.

[Interpreting the Methods for Blending Decoctions to Treat 60 Ailments in Tianhui bamboo slip medical manuscripts].

Among the medical texts excavated in 2012-2013 from the Han Dynasty tomb at Tianhui township in Sichuan province, we found a collection on the treatment of 60 ailments. Under each ailment, we found one or more formulas, for a total of 106 formulas. The authors of this paper compiled and analyzed these texts based on the original bamboo slips and named this collection with the title Methods for Blending Decoctions to Treat 60 Ailments because the content was focused on blending and making medicinal formulas, and also due to the historical connections with the texts the Record of the Court Scribe, "Biography of Bian Que and Cang Gong". For these reasons, this title was determined, where "blending decoctions" mean "blending and harmonizing medicines optimally in preparation for decocting". The Tianhui texts preserve ancient forms of medicinal formulas, including some once believed to be lost, such as "grain decoctions", "fermented alcohol decoctions", and "fiery decoctions". Based on the historical evidence, we can now ascertain that this text is the "Blending Formulas and Making Decoctions" mentioned in the Record of the Court Scribe written by Cang Gong. Moreover, the medical texts, Canon Formulas in Decoction Form (from the book of Han Dynasty) and the Imperial Pharmacy Formulas to Benefit the People in Song Dynasty are both of this genre of medical literature. The Tianhui text is therefore a representative of this genre of literature in the Western and eastern Han, acting as a key link between early medical formula books and later formula books.

Graphene Ambipolar Nanoelectronics for High Noise Rejection Amplification.

In a modern wireless communication system, signal amplification is critical for overcoming losses during multiple data transformations/processes and long-distance transmission. Common mode and differential mode are two fundamental amplification mechanisms, and they utilize totally different circuit configurations. In this paper, we report a new type of dual-gate graphene ambipolar device with capability of operating under both common and differential modes to realize signal amplification. The signal goes through two stages of modulation where the phase of signal can be individually modulated to be either in-phase or out-of-phase at two stages by exploiting the ambipolarity of graphene. As a result, both common and differential mode amplifications can be achieved within one single device, which is not possible in the conventional circuit configuration. In addition, a common-mode rejection ratio as high as 80 dB can be achieved, making it possible for low noise circuit application. These results open up new directions of graphene-based ambipolar electronics that greatly simplify the RF circuit complexity and the design of multifunction device operation.

Optical Control of Mechanical Mode-Coupling within a MoS2 Resonator in the Strong-Coupling Regime.

Two-dimensional (2-D) materials including graphene and transition metal dichalcogenides (TMDs) are an exciting platform for ultrasensitive force and displacement detection in which the strong light-matter coupling is exploited in the optical control of nanomechanical motion. Here we report the optical excitation and displacement detection of a ∼ 3 nm thick MoS2 resonator in the strong-coupling regime, which has not previously been achieved in 2-D materials. Mechanical mode frequencies can be tuned by more than 12% by optical heating, and they exhibit avoided crossings indicative of strong intermode coupling. When the membrane is optically excited at the frequency difference between vibrational modes, normal mode splitting is observed, and the intermode energy exchange rate exceeds the mode decay rate by a factor of 15. Finite element and analytical modeling quantifies the extent of mode softening necessary to control intermode energy exchange in the strong coupling regime.

Ultrafast Lateral Photo-Dember Effect in Graphene Induced by Nonequilibrium Hot Carrier Dynamics.

The photo-Dember effect arises from the asymmetric diffusivity of photoexcited electrons and holes, which creates a transient spatial charge distribution and hence the buildup of a voltage. Conventionally, a strong photo-Dember effect is only observed in semiconductors with a large asymmetry between the electron and hole mobilities, such as in GaAs or InAs, and is considered negligible in graphene due to its electron-hole symmetry. Here, we report the observation of a strong lateral photo-Dember effect induced by nonequilibrium hot carrier dynamics when exciting a graphene-metal interface with a femtosecond laser. Scanning photocurrent measurements reveal the extraction of photoexcited hot carriers is driven by the transient photo-Dember field, and the polarity of the photocurrent is determined by the device's mobility asymmetry. Furthermore, ultrafast pump-probe measurements indicate the magnitude of photocurrent is related to the hot carrier cooling rate. Our simulations also suggest that the lateral photo-Dember effect originates from graphene's 2D nature combined with its unique electrical and optical properties. Taken together, these results not only reveal a new ultrafast photocurrent generation mechanism in graphene but also suggest new types of terahertz sources based on 2D nanomaterials.

[Abnormal percentage of memory B cells in tonsils and peripheral blood in clinical progression of IgA nephropathy].

OBJECTIVE: To observe an abnormal expression of humoral immune response induced by memory B cells in tonsils and peripheral blood of patients with IgA nephropathy (IgAN), the variation of memory B cells after tonsillectomy, and to discover the role of tonsillectomy in IgAN. METHODS: In the study, 28 patients were diagnosed as IgAN via renal biopsy, and 27 patients suffering from chronic tonsillitis without nephritis and 10 normal human beings were selected as controls. The expression of memory B cells in the tonsils and peripheral blood was tested by flow cytometry, and the same method was used to test the variation of the expression of memory B cells in peripheral blood of patients with IgAN after tonsillectomy. RESULTS: In this study, higher percentages of memory B cells were observed in tonsil and peripheral blood of IgAN patients, which were 5.72%±5.26%, 4.92%±5.10%. After tonsillectomy, the percentage of memory B cells was 1.10%±0.65%, lower than that before tonsillectomy (P<0.05). Meanwhile, in tonsils and peripheral blood, the percentage of memory B cells varied with the variation of the urinary findings of the IgAN patients. CONCLUSION: The percentage of memory B cell in tonsils and peripheral blood could predict disease progression of IgAN to a certain extent.

Global research trends in DNA methylation in rheumatoid arthritis: A bibliometric analysis and visual analysis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder with a significant global economic burden. Epigenetic modifications, particularly DNA methylation, play a crucial role in RA. This study conducted a bibliometric analysis to explore the evolving trends and predominant themes in RA and DNA methylation research over the past two decades. A total of 1800 articles met the inclusion criteria, and the analysis revealed consistent growth in the literature, with a notable increase in output after 2019. The research involved 70 countries, 2139 academic institutions, 23,365 unique authors, and 58,636 co-cited authors. The United States emerged as a dominant contributor in this research domain. The significance of DNA methylation in shaping research directions for RA management is increasingly evident. Recent investigations have shed light on the pivotal role of DNA methylation in RA, particularly in characterizing synovial tissue and exploring the underlying mechanisms of disease pathogenesis. This study provides valuable insights into the landscape of DNA methylation research in RA and highlights the importance of epigenetics in autoimmune diseases.

Coherent control of enhanced second-harmonic generation in a plasmonic nanocircuit using a transition metal dichalcogenide monolayer.

Nonlinear nanophotonic circuits, renowned for their compact form and integration capabilities, hold potential for advancing high-capacity optical signal processing. However, limited practicality arises from low nonlinear conversion efficiency. Transition metal dichalcogenides (TMDs) could present a promising avenue to address this challenge, given their superior optical nonlinear characteristics and compatibility with diverse device platforms. Nevertheless, this potential remains largely unexplored, with current endeavors predominantly focusing on the demonstration of TMDs' coherent nonlinear signals via free-space excitation and collection. In this work, we perform direct integration of TMDs onto a plasmonic nanocircuitry. By controlling the polarization angle of the input laser, we show selective routing of second-harmonic generation (SHG) signals from a MoSe2 monolayer within the plasmonic circuit. Routing extinction ratios of 14.86 dB are achieved, demonstrating good coherence preservation in this hybrid nanocircuit. Additionally, our characterization indicates that the integration of TMDs leads to a 13.8-fold SHG enhancement, compared with the pristine nonlinear plasmonic nanocircuitry. These distinct features-efficient SHG generation, coupling, and controllable routing-suggest that our hybrid TMD-plasmonic nanocircuitry could find immediate applications including on-chip optical frequency conversion, selective routing, switching, logic operations, as well as quantum operations.

Engineering customized nanovaccines for enhanced cancer immunotherapy.

Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized nanovaccines through modification or functionalization has emerged as a promising approach. These tailored nanovaccines not only enhance antigen presentation, but also effectively modulate immunosuppression within the tumor microenvironment. Specifically, they are distinguished by their diverse sizes, shapes, charges, structures, and unique physicochemical properties, along with targeting ligands. These features of nanovaccines facilitate lymph node accumulation and activation/regulation of immune cells. This overview of bespoke nanovaccines underscores their potential in both prophylactic and therapeutic applications, offering insights into their future development and role in cancer immunotherapy.

Elevated polyclonal IgG4 mimicking a monoclonal gammopathy in IgG4-related disease-a case-based review.

IgG4-related diseases (IgG-RDs) are a group of fibroinflammatory diseases that affect a variety of tissues, resulting in tumour-like effects and/or organ dysfunction. Monoclonal gammopathies (MGPs) are a group of disorders characterized by clonal proliferation of plasma cells or lymphoid cells resulting in the secretion of a monoclonal immunoglobulin. Cases of MGPs in IgG4-RDs coexisting with plasma cell dyscrasias and lymphoid neoplasms have been reported over the past few years. Therefore, the results of examinations of M protein in IgG4-RD patients should be interpreted with caution. Herein, we report the case of a 58-year-old male with a history of type 2 diabetes who presented with submandibular masses, anosmia, swollen lymph nodes, proteinuria, and renal impairment. Laboratory tests revealed hyperglobulinemia and elevated levels of IgG4 (124 g/L) and serum-free light chains (sFLCs). Serum protein electrophoresis (SPEP) revealed an M spike of 5.6 g/dL, and immunofixation electrophoresis (IPE) revealed biclonal IgG-κ and IgG-λ. The patient underwent bone marrow, lymph node, and kidney biopsy, which ruled out plasma cell disorders and lymphoma. He was finally diagnosed with an IgG4-RD comorbid with diabetic nephropathy. The findings in this case highlight that significant activation of B cells in IgG4-RD patients, especially those with multiorgan involvement can lead to significant hyperglobulinemia and high sFLC and IgG4 levels, which are more pronounced in the setting of renal impairment. Relatively high concentrations of polyclonal IgG4 can give rise to a focal band bridging the ß and γ fractions, which may mimic the appearance of a monoclonal band on SPEP and monoclonal gammaglobulinemia in IFE. The patient experienced considerable improvement in his symptoms after rituximab combined with glucocorticoid therapy, and a monoclonal immunoglobulin was not detected.

Agronomic, physiological and transcriptional characteristics provide insights into fatty acid biosynthesis in yellowhorn (Xanthoceras sorbifolium Bunge) during fruit ripening.

Yellowhorn (Xanthoceras sorbifolium Bunge) is an oil-bearing tree species in northern China. In this study, we used yellowhorn from Heilongjiang to analyze the morphological and physiological changes of fruit development and conducted transcriptome sequencing. The results showed that the fruit experienced relatively slow growth from fertilization to DAF20 (20 days after flowering). From DAF40 to DAF60, the fruit entered an accelerated development stage, with a rapid increase in both transverse and longitudinal diameters, and the kernel contour developed completely at DAF40. From DAF60 to DAF80, the transverse and vertical diameters of the fruit developed slowly, and the overall measures remained stable until maturity. The soluble sugar, starch, and anthocyanin content gradually accumulated until reaching a peak at DAF80 and then rapidly decreased. RNA-seq analysis revealed differentially expressed genes (DEGs) in the seed coat and kernel, implying that seed components have different metabolite accumulation mechanisms. During the stages of seed kernel development, k-means clustering separated the DEGs into eight sub-classes, indicating gene expression shifts during the fruit ripening process. In subclass 8, the fatty acid biosynthesis pathway was enriched, suggesting that this class was responsible for lipid accumulation in the kernel. WGCNA revealed ten tissue-specific modules for the 12 samples among 20 modules. We identified 54 fatty acid biosynthesis pathway genes across the genome, of which 14 was quantified and confirmed by RT-qPCR. Most genes in the plastid synthesis stage showed high expression during the DAF40-DAF60 period, while genes in the endoplasmic reticulum synthesis stage showed diverse expression patterns. EVM0012847 (KCS) and EVM0002968 (HCD) showed similar high expression in the early stages and low expression in the late stages. EVM0022385 (HCD) exhibited decreased expression from DAF40 to DAF60 and then increased from DAF60 to DAF100. EVM0000575 (KCS) was increasingly expressed from DAF40 to DAF60 and then decreased from DAF60 to DAF100. Finally, we identified transcription factors (TFs) (HB-other, bHLH and ARF) that were predicted to bind to fatty acid biosynthesis pathway genes with significant correlations. These results are conducive to promoting the transcriptional regulation of lipid metabolism and the genetic improvement in terms of high lipid content of yellowhorn.

Neutrophil hitchhiking nanoparticles enhance bacteria-mediated cancer therapy via NETosis reprogramming.

Bacteria have shown great potential in anti-tumor treatment, and an attenuated strain of Salmonella named VNP20009 has been shown to be safe in clinical trials. However, colonized bacteria recruit neutrophils into the tumor, which release NETs to capture and eliminate bacteria, compromising bacterial-based tumor treatment. In this study, we report a neutrophil hitchhiking nanoparticles (SPPS) that block the formation of NET to enhance bacteria-mediated tumor therapy. In the 4 T1 tumor-bearing mouse model, following 24 h of bacterial therapy, there was an approximately 3.0-fold increase in the number of neutrophils in the bloodstream, while the amount of SPPS homing to tumor tissue through neutrophil hitchhiking increased approximately 2.0-fold. It is worth noting that the NETs in tumors significantly decreased by approximately 2.0-fold through an intracellular ROS scavenging-mediated NETosis reprogramming, thereby increasing bacterial vitality by 1.9-fold in tumors. More importantly, the gene drug (siBcl-2) loaded in SPPS can be re-encapsulated in apoptotic bodies by reprogramming neutrophils from NETosis to apoptosis, and enable the redelivery of drugs to tumor cells, further boosting the antitumor efficacy with a synergistic effect, resulting in about 98% tumor inhibition rate and 90% survival rate.