The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity.

Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance. Myeloid-specific IRE1α abrogation in Ern1f/f; Lyz2-Cre mice largely reversed high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity, insulin resistance, hyperlipidemia and hepatic steatosis. Brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly higher in Ern1f/f; Lyz2-Cre mice. Furthermore, IRE1α ablation augmented M2 polarization of macrophages in a cell-autonomous manner. Thus, IRE1α senses protein unfolding and metabolic and immunological states, and consequently guides ATM polarization. The macrophage IRE1α pathway drives obesity and metabolic syndrome through impairing BAT activity and WAT browning.

LncRNAs: the missing link to senescence nuclear architecture.

During cellular senescence and organismal aging, cells display various molecular and morphological changes. Although many aging-related long noncoding RNAs (lncRNAs) are highly associated with senescence-associated secretory phenotype, the roles of lncRNAs in senescence-associated nuclear architecture and morphological changes are just starting to emerge. Here I review lncRNAs associated with nuclear structure establishment and maintenance, their aging-related changes, and then focus on the pervasive, yet underappreciated, role of RNA double-strand DNA triplexes for lncRNAs to recognize targeted genomic regions, making lncRNAs the nexus between DNA and proteins to regulate nuclear structural changes. Finally, I discuss the future of deciphering direct links of lncRNA changes to various nuclear morphology changes assisted by artificial intelligence and genetic perturbations.

Unraveling aging from transcriptomics.

Research into aging constitutes a pivotal endeavor aimed at elucidating the underlying biological mechanisms governing aging and age-associated diseases, as well as promoting healthy longevity. Recent advances in transcriptomic technologies, such as bulk RNA sequencing (RNA-seq), single-cell transcriptomics, and spatial transcriptomics, have revolutionized our ability to study aging at unprecedented resolution and scale. These technologies present novel opportunities for the discovery of biomarkers, elucidation of molecular pathways, and development of targeted therapeutic strategies for age-related disorders. This review surveys recent breakthroughs in different types of transcripts on aging, such as mRNA, long noncoding (lnc)RNA, tRNA, and miRNA, highlighting key findings and discussing their potential implications for future studies in this field.

Ageing induces tissue-specific transcriptomic changes in Caenorhabditis elegans.

Ageing is a complex process with common and distinct features across tissues. Unveiling the underlying processes driving ageing in individual tissues is indispensable to decipher the mechanisms of organismal longevity. Caenorhabditis elegans is a well-established model organism that has spearheaded ageing research with the discovery of numerous genetic pathways controlling its lifespan. However, it remains challenging to dissect the ageing of worm tissues due to the limited description of tissue pathology and access to tissue-specific molecular changes during ageing. In this study, we isolated cells from five major tissues in young and old worms and profiled the age-induced transcriptomic changes within these tissues. We observed a striking diversity of ageing across tissues and identified different sets of longevity regulators therein. In addition, we found novel tissue-specific factors, including irx-1 and myrf-2, which control the integrity of the intestinal barrier and sarcomere structure during ageing respectively. This study demonstrates the complexity of ageing across worm tissues and highlights the power of tissue-specific transcriptomic profiling during ageing, which can serve as a resource to the field.

Author Correction: Molecular architecture of lineage allocation and tissue organization in early mouse embryo.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Molecular architecture of lineage allocation and tissue organization in early mouse embryo.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Molecular architecture of lineage allocation and tissue organization in early mouse embryo.

During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state1. Concurrently, germ layers are formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mapping and lineage-analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation2-5. The regionalization of cell fates preceding the formation of the basic body plan-the mechanisms of which are instrumental for understanding embryonic programming and stem-cell-based translational study-is conserved in vertebrate embryos6-8. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of the post-implantation embryo has yet to be undertaken. Here we report a spatially resolved transcriptome of cell populations at defined positions in the germ layers during development from pre- to late-gastrulation stages. This spatiotemporal transcriptome provides high-resolution digitized in situ gene-expression profiles, reveals the molecular genealogy of tissue lineages and defines the continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning, supports a role of Hippo-Yap signalling in germ-layer development and reveals the contribution of visceral endoderm to the endoderm in the early mouse embryo.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure.

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. DISCUSSION: Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF.

Voltage-Controlled Magnon Transistor via Tuning Interfacial Exchange Coupling.

Magnon transistors that can effectively regulate magnon transport by an electric field are desired for magnonics, which aims to provide a Joule-heating free alternative to the conventional electronics owing to the electric neutrality of magnons (the key carriers of spin-angular momenta in the magnonics). However, also due to their electric neutrality, magnons have no access to directly interact with an electric field and it is thus difficult to manipulate magnon transport by voltages straightforwardly. Here, we demonstrated a gate voltage (V_{g}) applied on a nonmagnetic metal and magnetic insulator (MI) interface that bent the energy band of the MI and then modulated the probability for conduction electrons in the nonmagnetic metal to tunnel into the MI, which can consequently enhance or weaken the spin-magnon conversion efficiency at the interface. A voltage-controlled magnon transistor based on the magnon-mediated electric current drag (MECD) effect in a Pt-Y_{3}Fe_{5}O_{12}-Pt sandwich was then experimentally realized with V_{g} modulating the magnitude of the MECD signal. The obtained efficiency (the change ratio between the MECD voltage at ±V_{g}) reached 10%/(MV/cm) at 300 K. This prototype of magnon transistor offers an effective scheme to control magnon transport by a gate voltage.

Belimumab therapy for refractory immune thrombocytopenia in systemic lupus erythematosus patients with anti-phospholipid antibodies.

OBJECTIVE: To observe the effect of belimumab treatment in refractory anti-phospholipid antibody-associated immune thrombocytopenia with systemic lupus erythematosus (SLE). METHOD: Four SLE patients with refractory anti-phospholipid antibody-associated immune thrombocytopenia were included in this one-arm observational study. Inclusion criteria were a diagnosis of SLE according to 1997 American College of Rheumatology criteria, severe immune thrombocytopenia (platelets <30 × 109/L), no bleeding symptoms, lack of satisfactory response to traditional treatment, and high-titre anti-phospholipid antibodies. All patients received belimumab (Benlysta®) for 6 months. RESULTS: The mean platelet count was 21.8 × 109 cells/L, ranging between 16 and 29 × 109/L at baseline, 123.3 × 109/L at 1 month, and 172.5 × 109/L at the end of 6 months after belimumab treatment. No bleeding complications occurred during the entire follow-up period. CONCLUSION: In this study, belimumab reduced the anti-phospholipid antibodies while increasing the platelet count in SLE patients with anti-phospholipid antibody-associated immune thrombocytopenia.

Integrative genomic analysis of early neurogenesis reveals a temporal genetic program for differentiation and specification of preplate and Cajal-Retzius neurons.

Neurogenesis in the developing neocortex begins with the generation of the preplate, which consists of early-born neurons including Cajal-Retzius (CR) cells and subplate neurons. Here, utilizing the Ebf2-EGFP transgenic mouse in which EGFP initially labels the preplate neurons then persists in CR cells, we reveal the dynamic transcriptome profiles of early neurogenesis and CR cell differentiation. Genome-wide RNA-seq and ChIP-seq analyses at multiple early neurogenic stages have revealed the temporal gene expression dynamics of early neurogenesis and distinct histone modification patterns in early differentiating neurons. We have identified a new set of coding genes and lncRNAs involved in early neuronal differentiation and validated with functional assays in vitro and in vivo. In addition, at E15.5 when Ebf2-EGFP+ cells are mostly CR neurons, single-cell sequencing analysis of purified Ebf2-EGFP+ cells uncovers molecular heterogeneities in CR neurons, but without apparent clustering of cells with distinct regional origins. Along a pseudotemporal trajectory these cells are classified into three different developing states, revealing genetic cascades from early generic neuronal differentiation to late fate specification during the establishment of CR neuron identity and function. Our findings shed light on the molecular mechanisms governing the early differentiation steps during cortical development, especially CR neuron differentiation.

A single-cell resolution developmental atlas of hematopoietic stem and progenitor cell expansion in zebrafish.

During vertebrate embryogenesis, fetal hematopoietic stem and progenitor cells (HSPCs) exhibit expansion and differentiation properties in a supportive hematopoietic niche. To profile the developmental landscape of fetal HSPCs and their local niche, here, using single-cell RNA-sequencing, we deciphered a dynamic atlas covering 28,777 cells and 9 major cell types (23 clusters) of zebrafish caudal hematopoietic tissue (CHT). We characterized four heterogeneous HSPCs with distinct lineage priming and metabolic gene signatures. Furthermore, we investigated the regulatory mechanism of CHT niche components for HSPC development, with a focus on the transcription factors and ligand-receptor networks involved in HSPC expansion. Importantly, we identified an endothelial cell-specific G protein-coupled receptor 182, followed by in vivo and in vitro functional validation of its evolutionally conserved role in supporting HSPC expansion in zebrafish and mice. Finally, comparison between zebrafish CHT and human fetal liver highlighted the conservation and divergence across evolution. These findings enhance our understanding of the regulatory mechanism underlying hematopoietic niche for HSPC expansion in vivo and provide insights into improving protocols for HSPC expansion in vitro.

Comparative investigation of transport and deposition of nebulized particles in nasal airways following various middle turbinectomy.

BACKGROUND: Topical intranasal medication is required following functional endoscopic sinus surgery (FESS). The optimal particle size of transnasal nebulization aimed at the sinonasal cavities is not conclusive. The current study aims to evaluate the effect of particle size and various surgery scope of middle turbinectomy (MT) on post-full FESS drug delivery to the sinonasal cavities. METHODS: Sinonasal reconstructions were performed from post-full FESS CT scans in 6 chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Four additional models representing alternative surgery scopes of MT were established from each post-FESS reconstruction for simulation data comparison. Airflow and particle deposition of nebulized delivery were simulated via computational fluid dynamics (CFD) and validated through in vitro experiments. The optimal particle sizes reaching a deposition of at least 75% of the maximum in the targeted regions were identified. RESULTS: The drug deposition rate onto the targeted regions increased following MT, with the greatest deposition following posterior MT (P-MT). Droplets in the range of 18-26 λm reached a deposition of larger than 75% of the maximum onto the targeted regions. Drug delivery rate in the sinonasal cavities varied significantly among individuals and across different types of MT with varying surgical scopes. CONCLUSIONS: This study is the first to investigate the effect of various surgery scope on drug delivery by transnasal nebulization to the sinonasal cavities. The findings strongly affirm the vast potential of transnasal nebulization as an effective post-FESS treatment option. Moreover, it emphasizes that the drug delivery process via atomizers to the nasal cavity and paranasal sinuses is highly sensitive to the particle size.

Limosilactobacillus reuteri peptidoglycan alleviates aflatoxin B1-induced toxicity through adsorbing toxins and improving growth, antioxidant status, immunity and liver pathological changes in chicks.

1. The objective of this study was to investigate the protective effects of a peptidoglycan produced by Limosilactobacillus reuteri against aflatoxin B1 (AFB1) induced toxicity in vitro and in vivo in broiler chicks.2. Toxin adsorption experiments were carried out firstly in vitro. These experiments indicated that the absorption efficiency of the peptidoglycan for AFB1 was 64.3-75.9%.3. In the in vivo experiments, Hy-Line Brown chicks were fed a diet containing AFB1 at 71.43 µg/kg with and without peptidoglycan supplementation at concentrations of 100, 200, or 300 g/kg feed from 0-42 d of age.4. The peptidoglycan supplementation in AFB1-contaminated diets resulted in significant improvements in terms of average daily gain, feed intake, feed conversion ratio, white blood cell count, haemoglobin content, glutathione peroxidase activity, immunoglobulin (Ig) A, IgG, IgM and Newcastle disease virus antibody titres (p < 0.05) and diminished liver steatosis.5. In conclusion, peptidoglycan supplementation alleviated AFB1-induced toxicity through adsorbing toxins and improving growth performance, antioxidant ability, immunity and liver pathological changes in chicks. The optimal supplemental dose was 200 mg/kg in feed.

[Mid- and long-term outcomes of percutaneous balloon mitral valvuloplasty guided solely by echocardiography].

Objective: To evaluate the mid-and long-term clinical outcomes of percutaneous balloon mitral valvuloplasty (PBMV) guided solely by echocardiography. Methods: A total of 71 patients with moderate to severe mitral stenosis who underwent PBMV guided solely by echocardiography at Fuwai Hospital, Chinese Academy of Medical Sciences, from January 2016 to December 2022 were retrospectively included. The clinical data and follow-up information were collected and analyzed. Results: Finally, 71 patients (11 males and 60 females) aged (48.6±12.4) years, including 3 pregnant women were included. One patient required surgical intervention due to moderate to severe mitral regurgitation, resulting in a procedure success rate of 98.6% (70/71). The procedural duration was (84.1±40.2) minutes, with the balloon diameter of (26.5±1.1) mm and number of dilatations of 2.9±0.7. The mean mitral transvalvular pressure gradient decreased from (12.6±6.1) mmHg (1 mmHg=0.133 kPa) preoperatively to (5.4±2.4) mmHg postoperatively, while the mitral valve orifice area increased from (0.9±0.2) cm² to (1.7±0.3) cm² (both P<0.001). Before discharge, 16 patients developed new mild mitral regurgitation, five developed new moderate mitral regurgitation, and one patient had a small amount of pericardial effusion absorbed by herself. No severe complications such as death, pericardial tamponade, or thromboembolism occurred during the perioperative period. The average follow-up duration was 12-84 (49.7±21.4) months. At two years postoperatively, the mean mitral transvalvular pressure gradient was (6.2±2.5) mmHg, and the mitral valve orifice area was (1.6±0.3) cm². Eight patients underwent surgical mitral valve replacement at an median of [M(Q1, Q3)] 18 (5, 53) months postoperatively, and one patient died during the follow-up period due to non-cardiac reasons. Conclusion: The mid-and long-term outcomes of PBMV guided solely by echocardiography are favorable.

[Intermittent exotropia complicated with spasm of the near reflex: a case report].

A 21-year-old female patient presented to the Ophthalmology Department of Yunnan University Affiliated Hospital with complaints of "bilateral blurred vision accompanied by diplopia for 3 weeks". The patient's main symptoms included intermittent visual blurring, diplopia, headaches, and ocular discomfort. Ocular examination revealed intermittent exotropia, sometimes accompanied by esotropia or orthotropia, along with signs of pupillary constriction and pseudomyopia. Based on the clinical presentation, a diagnosis of intermittent exotropia complicated by spasm of the near reflex (SNR) was made. The patient underwent bilateral exotropia surgery, which corrected the ocular alignment and resolved the symptoms and signs of SNR postoperatively.

[Analysis factors influencing left ventricular thrombus in patients with non-ischemic heart failure].

Objective: To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT. Methods: This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model. Results: A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) µg/L vs. 158 (68, 379) µg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group (P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF (OR=1.08, 95%CI 1.02-1.15, P=0.008), decreased LVESD (OR=1.07, 95%CI 1.01-1.12, P=0.013), and increased D-dimer levels (OR=5.40, 95%CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95%CI 0.710-0.876, P<0.001). Conclusion: Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

[Early experience with mechanical hemodynamic support for catheter ablation of malignant ventricular tachycardia].

Objective: To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice. Methods: This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed. Results: A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up. Conclusions: MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

[Research progress on the application of non-nutritional effects of fat emulsion in the treatment of poisoning].

Fat emulsion is a drug commonly used clinically for parenteral nutrition support in critically ill patients.With the development of the pharmaceutical industry, fat emulsion has formed a variety of different formulations, among which different types of fat emulsion have their own metabolic and body energy supply characteristics, and the application indications are also different. In addition to providing the supply of nutrients, the role of fat emulsion in anti-toxicity, immune regulation, anti-inflammatory, anti-shock, cardiopulmonary resuscitation and other aspects has gradually been discovered. This article reviews the existing evidence-based medical evidence and expounds the mechanism and therapeutic role of fat emulsion in the treatment of critically ill patients with poisoning. Its value in the treatment of critically ill patients with poisoning was discussed, and some references were provided for the application of non-nutritional functions of fat emulsion in the future.

Fully reconfigurable MEMS-based second-order coupled-resonator optical waveguide (CROW) with ultra-low tuning energy.

Integrated microring resonators are well suited for wavelength-filtering applications in optical signal processing, and cascaded microring resonators allow flexible filter design in coupled-resonator optical waveguide (CROW) configurations. However, the implementation of high-order cascaded microring resonators with high extinction ratios (ERs) remains challenging owing to stringent fabrication requirements and the need for precise resonator tunability. We present a fully integrated on-chip second-order CROW filter using silicon photonic microelectromechanical systems (MEMS) to adjust tunable directional couplers and a phase shifter using nanoscale mechanical out-of-plane waveguide displacement. The filter can be fully reconfigured with regard to both the ER and center wavelength. We experimentally demonstrated an ER exceeding 25 dB and continuous wavelength tuning across the full free spectral range of 0.123 nm for single microring resonator, and showed reconfigurability in second-order CROW by tuning the ER and resonant wavelength. The tuning energy for an individual silicon photonic MEMS phase shifter or tunable coupler is less than 22 pJ with sub-microwatt static power consumption, which is far better than conventional integrated phase shifters based on other physical modulation mechanisms.