3D-printed machines that manipulate microscopic objects using capillary forces.

Objects that deform a liquid interface are subject to capillary forces, which can be harnessed to assemble the objects1-4. Once assembled, such structures are generally static. Here we dynamically modulate these forces to move objects in programmable two-dimensional patterns. We 3D-print devices containing channels that trap floating objects using repulsive capillary forces5,6, then move these devices vertically in a water bath. Because the channel cross-sections vary with height, the trapped objects can be steered in two dimensions. The device and interface therefore constitute a simple machine that converts vertical to lateral motion. We design machines that translate, rotate and separate multiple floating objects and that do work on submerged objects through cyclic vertical motion. We combine these elementary machines to make centimetre-scale compound machines that braid micrometre-scale filaments into prescribed topologies, including non-repeating braids. Capillary machines are distinct from mechanical, optical or fluidic micromanipulators in that a meniscus links the object to the machine. Therefore, the channel shapes need only be controlled on the scale of the capillary length (a few millimetres), even when the objects are microscopic. Consequently, such machines can be built quickly and inexpensively. This approach could be used to manipulate micrometre-scale particles or to braid microwires for high-frequency electronics.

CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6.

BACKGROUND: T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear. METHODS: Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell-specific LGMN-knockout) mice (Lgmnf/f/CD4Cre), regulatory T cell (Treg)-specific LGMN-knockout mice (Lgmnf/f/Foxp3YFP Cre), and RR-11a (LGMN inhibitor)-treated C57BL/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development. RESULTS: LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II-induced or deoxycorticosterone acetate/salt-induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II-induced or deoxycorticosterone acetate/salt-induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II-induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II-induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor-associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-κB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II-induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects. CONCLUSIONS: LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.

Fibration of powdery materials.

Non-destructive processing of powders into macroscopic materials with a wealth of structural and functional possibilities has immeasurable scientific significance and application value, yet remains a challenge using conventional processing techniques. Here we developed a universal fibration method, using two-dimensional cellulose as a mediator, to process diverse powdered materials into micro-/nanofibres, which provides structural support to the particles and preserves their own specialties and architectures. It is found that the self-shrinking force drives the two-dimensional cellulose and supported particles to pucker and roll into fibres, a gentle process that prevents agglomeration and structural damage of the powder particles. We demonstrate over 120 fibre samples involving various powder guests, including elements, compounds, organics and hybrids in different morphologies, densities and particle sizes. Customized fibres with an adjustable diameter and guest content can be easily constructed into high-performance macromaterials with various geometries, creating a library of building blocks for different fields of applications. Our fibration strategy provides a universal, powerful and non-destructive pathway bridging primary particles and macroapplications.

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic phenotype. However, the function of HMGB2 in PH remains uninvestigated. METHODS: Smooth muscle cell (SMC)-specific HMGB2 knockout or HMGB2-OE (HMGB2 overexpression) mice and HMGB2 silenced rats were used to establish hypoxia+Su5416 (HySu)-induced PH mouse and monocrotaline-induced PH rat models, respectively. The effects of HMGB2 and its underlying mechanisms were subsequently elucidated using RNA-sequencing and cellular and molecular biology analyses. Serum HMGB2 levels were measured in the controls and patients with pulmonary arterial (PA) hypertension. RESULTS: HMGB2 expression was markedly increased in the PAs of patients with PA hypertension and PH rodent models and was predominantly localized in PASMCs. SMC-specific HMGB2 deficiency or silencing attenuated PH development and pulmonary vascular remodeling in hypoxia+Su5416-induced mice and monocrotaline-treated rats. SMC-specific HMGB2 overexpression aggravated hypoxia+Su5416-induced PH. HMGB2 knockdown inhibited PASMC proliferation in vitro in response to PDGF-BB (platelet-derived growth factor-BB). In contrast, HMGB2 protein stimulation caused the hyperproliferation of PASMCs. In addition, HMGB2 promoted PASMC proliferation and the development of PH by RAGE (receptor for advanced glycation end products)/FAK (focal adhesion kinase)-mediated Hippo/YAP (yes-associated protein) signaling suppression. Serum HMGB2 levels were significantly increased in patients with PA hypertension, and they correlated with disease severity, predicting worse survival. CONCLUSIONS: Our findings indicate that targeting HMGB2 might be a novel therapeutic strategy for treating PH. Serum HMGB2 levels could serve as a novel biomarker for diagnosing PA hypertension and determining its prognosis.

Engineering and functional analysis of yeast with a monotypic 40S ribosome subunit.

Emerging evidence reveals that ribosomes are not monolithic but dynamic machines with heterogeneous protein compositions that can reshape ribosomal translational abilities and cellular adaptation to environmental changes. Duplications of ribosomal protein (RP) genes are ubiquitous among organisms and are believed to affect cell function through paralog-specific regulation (e.g., by generating heterogeneous ribosomes) and/or gene dose amplification. However, direct evaluations of their impacts on cell function remain elusive due to the highly heterogeneous cellular RP pool. Here, we engineered a yeast with homogeneous 40S RP paralog compositions, designated homo-40S, by deleting the entire set of alternative duplicated genes encoding yeast 40S RP paralogs. Homo-40S displayed mild growth defects along with high sensitivity to the translation inhibitor paromomycin and a significantly increased stop codon readthrough. Moreover, doubling of the remaining RP paralogous genes in homo-40S rescued these phenotypes markedly, although not fully, compared to the wild-type phenotype, indicating that the dose of 40S RP genes together with the heterogeneity of the contents was vital for maintaining normal translational functionalities and growth robustness. Additional experiments revealed that homo-40S improved paromomycin tolerance via acquisition of bypass mutations or evolved to be diploid to generate fast-growing derivatives, highlighting the mutational robustness of engineered yeast to accommodate environmental and genetic changes. In summary, our work demonstrated that duplicated RP paralogs impart robustness and phenotypic plasticity through both gene dose amplification and paralog-specific regulation, paving the way for the direct study of ribosome biology through monotypic ribosomes with a homogeneous composition of specific RP paralogs.

HRD1 promotes non-small cell lung carcinoma metastasis by blocking autophagy-mediated MIEN1 degradation.

Dysregulation of autophagy has been implicated in the development of many diseases, including cancer. Here, we revealed a novel function of the E3 ubiquitin ligase HRD1 in non-small cell lung carcinoma (NSCLC) metastasis by regulating autophagy. Mechanistically, HRD1 inhibits autophagy by promoting ATG3 ubiquitination and degradation. Additionally, a pro-migratory and invasive factor, MIEN1 (migration and invasion enhancer 1), was found to be autophagically degraded upon HRD1 deficiency. Importantly, expression of both HRD1 and MIEN1 are upregulated and positively correlated in lung tumors. Based on these results, we proposed a novel mechanism of HRD1 function that the degradation of ATG3 protein by HRD1 leads to autophagy inhibition and MIEN1 release, thus promoting NSCLC metastasis. Therefore, our findings provided new insights into the role of HRD1 in NSCLC metastasis and new therapeutic targets for lung cancer treatment.

HER2-low heterogeneity between primary and paired recurrent/metastatic breast cancer: Implications in treatment and prognosis.

BACKGROUND: With the largest sample size to date, the authors' objective was to investigate the incidence of primary-to-metastatic human epidermal growth factor 2 (HER2) conversion and the predictors for such conversion. Moreover, no previous studies have evaluated the prognosis of patients who have negative HER2 expression (HER2-0) versus low HER2 expression (HER2-low) when HER2 status was assessed based on all recurrent/metastatic lesions. METHODS: The authors included 1299 patients who had available HER2 status of primary breast tumors and paired recurrent/metastatic lesions at Fudan University Shanghai Cancer Center and West China Hospital. RESULTS: In total, 370 patients (28.5%) experienced primary-to-metastatic HER2 conversion. Intrapatient intermetastasis spatial heterogeneity and temporal heterogeneity of HER2 were detected. When assessing HER2 based on recurrent/metastatic tumors, patients who had HER2-0 tumors had significantly shorter overall survival than those who had HER2-low tumors in the overall population and in the estrogen receptor (ER)-negative subgroup. However, when assessing HER2 based on primary tumors, there was no difference in overall survival between patients who had HER2-0 versus HER2-low tumors. Moreover, patients who had tumors that converted from HER2-0 to HER2-low had longer overall survival than those who had consistent HER2-0 status in the ER-negative subgroup. By combining four predictors (ER status, Ki67 index, biopsy site, and disease-free interval), the authors established the first prediction tool to estimate the probability of HER2-0 tumors converting to HER2-low/positive tumors. CONCLUSIONS: Intrapatient primary-to-metastatic and intermetastatic HER2 heterogeneity were observed in this large-scale cohort study. When evaluating HER2 based on recurrent/metastatic tumors, an overall survival difference was observed between patients who had HER2-0 versus HER2-low, recurrent/metastatic breast tumors. The developed prediction tool might help clinicians screen out patients with primary HER2-0 tumors that have a high probability of HER2 status conversion and recommend them for re-biopsy, thus helping to screen out candidate patients for trastuzumab deruxtecan treatment.

Efficient sum-frequency generation of a yellow laser in a thin-film lithium niobate waveguide.

Yellow lasers with high efficiency and tunability play an essential role in many applications. Here, we demonstrate the sum-frequency generation (SFG) of yellow light on a periodically poled thin-film lithium niobate (PP-TFLN) waveguide. Taking advantage of large χ(2) nonlinearity, a high normalized conversion efficiency of 10,097% (W·cm2) is obtained with pump wavelengths of 1317.7 and 1064 nm. An absolute conversion efficiency of 24.17% is recorded with on-chip pump powers of 10.4 dBm (O-band) and 13.5 dBm (1064 nm).

Virtual-State Model for Analyzing Electro-Optical Modulation in Ring Resonators.

Ring resonators play a crucial role in optical communication and quantum technology applications. However, these devices lack a simple and intuitive theoretical model to describe their electro-optical modulation. When the resonance frequency is rapidly modulated, the filtering and modulation within a ring resonator become physically intertwined, making it difficult to analyze the complex physical processes involved. We address this by proposing an analytical solution for electro-optic ring modulators based on the concept of a "virtual state." This approach equates a lightwave passing through a dynamic ring modulator to one excited to a virtual state by a cumulative phase and then returning to the real state after exiting the static ring. Our model simplifies the independent analysis of the intertwined physical processes, enhancing its versatility in analyzing various incident signals and modulation formats. Experimental results, including resonant and detuning modulation, align with the numerical simulation of our model. Notably, our findings indicate that the dynamic modulation of the ring resonator under detuning driving approximates phase modulation.

Effect of frozen-thawed embryo transfer with a poor-quality embryo and a good-quality embryo on pregnancy and neonatal outcomes.

BACKGROUND: To evaluate the impact of embryo quality and quantity, specifically a poor quality embryo (PQE) in combination with a good quality embryo (GQE), by double embryo transfer (DET) on the live birth rate (LBR) and neonatal outcomes in patients undergoing frozen-thawed embryo transfer (FET) cycles. METHODS: A study on a cohort of women who underwent a total of 1462 frozen-thawed cleavage or blastocyst embryo transfer cycles with autologous oocytes was conducted between January 2018 and December 2021. To compare the outcomes between single embryo transfer (SET) with a GQE and DET with a GQE and a PQE, propensity score matching (PSM) was applied to control for potential confounders, and a generalized estimating equation (GEE) model was used to determine the association between the effect of an additional PQE and the outcomes. Subgroup analysis was also performed for patients stratified by female age. RESULTS: After PS matching, DET-GQE + PQE did not significantly alter the LBR (adjusted odds ratio [OR] 1.421, 95% CI 0.907-2.228) compared with SET-GQE in cleavage-stage embryo transfer but did increase the multiple birth rate (MBR, [OR] 3.917, 95% CI 1.189-12.911). However, in patients who underwent blastocyst-stage embryo transfer, adding a second PQE increased the live birth rate by 7.8% ([OR] 1.477, 95% CI 1.046-2.086) and the multiple birth rate by 19.6% ([OR] 28.355, 95% CI 3.926-204.790), and resulted in adverse neonatal outcomes. For patients who underwent cleavage-stage embryo transfer, transferring a PQE with a GQE led to a significant increase in the MBR ([OR] 4.724, 95% CI 1.121-19.913) in women under 35 years old but not in the LBR ([OR] 1.227, 95% CI 0.719-2.092). The increases in LBR and MBR for DET-GQE + PQE compared with SET-GQE in women older than 35 years were nonsignificant toward. For patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE had a greater LBR ([OR] 1.803, 95% CI 1.165-2.789), MBR ([OR] 24.185, 95% CI 3.285-178.062) and preterm birth rate (PBR, [OR] 4.092, 95% CI 1.153-14.518) than did SET-GQE in women under 35 years old, while no significant impact on the LBR ([OR] 1.053, 95% CI 0.589-1.884) or MBR (0% vs. 8.3%) was observed in women older than 35 years. CONCLUSIONS: The addition of a PQE has no significant benefit on the LBR but significantly increases the MBR in patients who underwent frozen-thawed cleavage-stage embryo transfer. However, for patients who underwent blastocyst-stage embryo transfer, DET-GQE + PQE resulted in an increase in both the LBR and MBR, which may lead to adverse neonatal outcomes. Thus, the benefits and risks of double blastocyst-stage embryo transfer should be balanced. In patients younger than 35 years, SET-GQE achieved satisfactory LBR either in cleavage-stage embryo transfer or blastocyst-stage embryo transfer, while DET-GQE + PQE resulted in a dramatically increased MBR. Considering the low LBR in women older than 35 years who underwent single cleavage-stage embryo transfer, selective single blastocyst-stage embryo transfer appears to be a more promising approach for reducing the risk of multiple live births and adverse neonatal outcomes.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Braiding, twisting, and weaving microscale fibers with capillary forces.

Soft materials made from braided or woven microscale fibers can display unique properties that can be exploited in electromagnetic, mechanical, and biomedical applications. These properties depend on the topology of the braids or weaves-that is, the order in which fibers cross one another. Current industrial braiding and weaving machines cannot easily braid or weave micrometer-scale fibers into controllable topologies; they typically apply forces that are large enough to break the fibers, and each machine can typically make only one topology. Here we use a 3D-printed device called a "capillary machine" to manipulate micrometer-scale fibers without breaking them. The operating principle is the physics of capillary forces: as the machines move vertically, they exert lateral capillary forces on floating objects, which in turn move small fibers connected to them. We present a new type of capillary machine that is based on principles of braid theory. It implements all the possible fiber-swapping operations for a set of four fibers and can therefore make any four-strand topology, including braids, twists, hierarchical twists, and weaves. We make these different topologies by changing the pattern of vertical motion of the machine. This approach is a mechanically simple, yet versatile way to make micro- and nano-textiles. We describe the prospects and limitations of this new type of machine for applications.

A confinement-regulated (H3C-NH3)+ ion as a smallest dual-wheel rotator showing bisected rotation dynamics.

On the basis of variable-temperature single-crystal X-ray diffraction, rotational energy barrier analysis, variable-temperature/frequency dielectric response, and molecular dynamics simulations, here we report a new crystalline supramolecular rotor (CH3NH3)(18-crown-6)[CuCl3], in which the (H3C-NH3)+ ion functions as a smallest dual-wheel rotator showing bisected rotation dynamics, while the host 18-crown-6 macrocycle behaves as a stator that is not strictly stationary. This study also provides a helpful insight into the dynamics of ubiquitous -CH3/-NH3 groups confined in organic or organic-inorganic hybrid solids.

Molecular rotators anchored on a rod-like anionic coordination polymer adhered by charge-assisted hydrogen bonds.

On the basis of variable-temperature single-crystal X-ray diffraction, variable-temperature/frequency dielectric analysis, variable-temperature solid-state nuclear magnetic resonance spectroscopy, and molecular dynamics simulations, here we present a new model of crystalline supramolecular rotor (i-PrNHMe2)[CdBr3], where a conformationally flexible near-spherical (i-PrNHMe2)+ cation functions as a rotator and a rod-like anionic coordination polymer {[CdBr3]-}∞ acts as the stator, and the adhesion of them is realized by charge-assisted hydrogen bonds.

Locally advanced breast cancer patients should be cautious about the immediate breast reconstruction after mastectomy: a pooling analysis of safety and efficacy.

BACKGROUND: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients. METHODS: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3. RESULTS: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group. CONCLUSIONS: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided.

Let-7b-5p inhibits colon cancer progression by prohibiting APC ubiquitination degradation and the Wnt pathway by targeting NKD1.

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/ß-catenin pathway, but it is highly expressed in colon cancer and can promote colon cancer cell proliferation. miRNAs are involved in the occurrence and progression of many tumors. However, miRNAs that can regulate NKD1 and the mechanisms by which NKD1 regulates tumor progression remain ambiguous. This research aims to reveal the potential regulatory network of NKD1 in colon cancer. miRNA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed by bioinformatics to screen for potential miRNAs targeting NKD1. Let-7b-5p was found to inhibit proliferation, migration, and invasion of colon cancer cells targeting NKD1. Further studies suggested that let-7b-5p can modulate Wnt signaling activity, and the nuclear accumulation of ß-catenin was significantly restrained by let-7b-5p through targeting NKD1. Moreover, NKD1 could prohibit the expression of the APC protein. Further studies manifested that NKD1 bound to APC and promoted the ubiquitination degradation of APC through restraining the expression of the deubiquitinating enzyme USP15 and blocking the combination between USP15 and APC. Functionally, NKD1 enhanced the proliferation and migration of colon cancer cells by inhibiting APC expression. This research revealed a novel mechanism by which the let-7b-5p-NKD1-APC-ß-catenin signaling pathway inhibited colon cancer cell progression.

Inhibition of ferroptosis protects sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a serious and common complication of sepsis. To study the ferroptosis in the pathogenesis of SAE and demonstrate the protection effect of ferroptosis resistance, cognitive function, neurological deficits, blood-brain barrier integrity and neuroinflammation were detected. SAE model was established by cecal ligation and puncture (CLP) in mice and an in vitro model was created by introducing LPS to HT22 cells. Ferroptosis inducer Fe-citrate (Fe) and ferroptosis inhibitor ferrostatin-1 (Fer-1) was post-treated in the models, respectively. SAE caused ferroptosis, as evidenced by an increase in reactive oxygen species (ROS), iron content and malondialdehyde (MDA) and a decrease in glutathione (GSH) level, as well as changes in the expression of ferroptosis-related proteins as acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and cystine-glutamate antiporter (SLC7A11), and harmed mitochondrial function. In contrast, inhibiting ferroptosis with Fer-1 attenuated ferroptosis. Meanwhile, Fer-1 attenuated neurologic severity score, learning and memory impairment, Fluoro-Jade C (FJC) staining, and decreased Evans Blue (EB) extravasation, microglia activation and TNF-α and IL-1ß production following SAE. The benefit of Fer-1 was diminished by ferroptosis inducer Fe. In addition, Fer-1 up-regulated the nuclear factor erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1(HO-1) signaling axis both in vivo and in vitro. In conclusion, our study revealed that Fer-1 might inhibit feroptosis in neurons by triggering the Nrf2/OH-1 pathway, thereby providing a therapeutic solution for SAE.

Ultra-broadband 1 × 2 3 dB power splitter using a thin-film lithium niobate from 1.2 to 2 µm wave band.

The 3 dB power splitters are fundamental building blocks for integrated photonic devices. As data capacity requirements continue to rise, there is a growing interest in integrated devices that can accommodate multiple spectral bands, including the conventional O-, C-, and L-bands, and the emerging 2 µm band. Here we propose and experimentally demonstrate a 3 dB power splitter based on adiabatic mode evolution using a thin-film lithium niobate, with ultra-broadband operation bandwidth from 1200 to 2100 nm. The fabricated power splitter exhibits low insertion losses of 0.2, 0.16, and 0.53 dB for wavelengths at 1310, 1550, and 2000 nm, respectively. The measured 1 dB bandwidth covers 1260-1360, 1480-1640, and 1930-2030 nm, which we believe that the proposed device is capable of operating in both O-, C-, L-, and 2 µm bands.

Prostaglandin and prostaglandin receptors: present and future promising therapeutic targets for pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling of the pulmonary arterioles, manifested by pulmonary vascular resistance (PVR) and increased pulmonary arterial pressure, eventually leading to right heart failure or even death. The mechanisms involved in this process include inflammation, vascular matrix remodeling, endothelial cell apoptosis and proliferation, vasoconstriction, vascular smooth muscle cell proliferation and hypertrophy. In this study, we review the mechanisms of action of prostaglandins and their receptors in PAH. MAIN BODY: PAH-targeted therapies, such as endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, activators of soluble guanylate cyclase, prostacyclin, and prostacyclin analogs, improve PVR, mean pulmonary arterial pressure, and the six-minute walk distance, cardiac output and exercise capacity and are licensed for patients with PAH; however, they have not been shown to reduce mortality. Current treatments for PAH primarily focus on inhibiting excessive pulmonary vasoconstriction, however, vascular remodeling is recalcitrant to currently available therapies. Lung transplantation remains the definitive treatment for patients with PAH. Therefore, it is imperative to identify novel targets for improving pulmonary vascular remodeling in PAH. Studies have confirmed that prostaglandins and their receptors play important roles in the occurrence and development of PAH through vasoconstriction, vascular smooth muscle cell proliferation and migration, inflammation, and extracellular matrix remodeling. CONCLUSION: Prostacyclin and related drugs have been used in the clinical treatment of PAH. Other prostaglandins also have the potential to treat PAH. This review provides ideas for the treatment of PAH and the discovery of new drug targets.

Denervation aggravates renal ischemia reperfusion injury via BMAL1-mediated Nrf2/ARE pathway.

AIM: To explore the change of clock gene rhythm under renal denervation (RDN) and its effect on renal function and oxidative stress during renal ischemia-reperfusion (IR) injury. METHOD: C57/BL6 mice were randomly divided into 4 groups at daytime 7 A M (zeitgeber time [ZT] 0) or at nighttime 7 P M (ZT12) in respectively: Sham (S) group, RDN group, IR group and RDN + IR (DIR) group. Renal pathological and functional changes were assessed by H&E staining, and serum creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin levels. Renal oxidative stress was detected by SOD and MDA levels, and renal inflammation was measured by IL-6, IL-17 A F and TNF-ɑ levels. BMAL1, CLOCK, Nrf2 and HO-1 mRNA and protein expressions were tested by qPCR and Western Blot. RESULT: Compared with S groups, the rhythm of BMAL1, CLOCK and Nrf2 genes in the kidney were disordered in RDN groups, while renal pathological and functional indexes did not change significantly. Compared with IR groups, renal pathological and functional indexes were significantly higher in the DIR groups, as well as oxidative stress and inflammation in renal tissues. The nocturnal IR injury in the RDN kidney was the worst while the BMAL1, Nrf2 and HO-1 expressions were the highest. In DIR groups, renal injury was aggravated after the Brusatol treatment, but there was no significant improvement after the t-BHQ treatment at night, which might be consistent with the changes of Nrf2 and HO-1 protein expressions. CONCLUSION: RDN lead to the disruption of BMAL1-mediated Nrf2 rhythm accumulation in the kidney, which reduced the renal ability to resist oxidative stress and inflammation, due to the impaired effect of activating Nrf2/ARE pathway in renal IR injury at nighttime.