Microbiota regulates intratumoral monocytes to promote anti-tumor immune responses.

The gut microbiota has been shown to promote the efficacy of cancer therapy through regulating adaptive immune responses. In this issue of Cell, Lam et al. provide new evidence demonstrating that specific gut bacteria also reprogram the innate immune tumor microenvironment to enhance the efficacy of cancer therapies.

Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization.

The intestine harbors a large population of resident eosinophils, yet the function of intestinal eosinophils has not been explored. Flow cytometry and whole-mount imaging identified eosinophils residing in the lamina propria along the length of the intestine prior to postnatal microbial colonization. Microscopy, transcriptomic analysis, and mass spectrometry of intestinal tissue revealed villus blunting, altered extracellular matrix, decreased epithelial cell turnover, increased gastrointestinal motility, and decreased lipid absorption in eosinophil-deficient mice. Mechanistically, intestinal epithelial cells released IL-33 in a microbiota-dependent manner, which led to eosinophil activation. The colonization of germ-free mice demonstrated that eosinophil activation in response to microbes regulated villous size alterations, macrophage maturation, epithelial barrier integrity, and intestinal transit. Collectively, our findings demonstrate a critical role for eosinophils in facilitating the mutualistic interactions between the host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.

Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs.

Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found here that production of the cytokine IL-15 by FRCs was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer's patches and mesenteric lymph nodes. Moreover, FRC-specific ablation of the innate immunological sensing adaptor MyD88 unleashed IL-15 production by FRCs during infection with an enteropathogenic virus, which led to hyperactivation of group 1 ILCs and substantially altered the differentiation of helper T cells. Accelerated clearance of virus by group 1 ILCs precipitated severe intestinal inflammatory disease with commensal dysbiosis, loss of intestinal barrier function and diminished resistance to colonization. In sum, FRCs act as an 'on-demand' immunological 'rheostat' by restraining activation of group 1 ILCs and thereby preventing immunopathological damage in the intestine.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Antenna-coupled infrared nanospectroscopy of intramolecular vibrational interaction.

Many photonic and electronic molecular properties, as well as chemical and biochemical reactivities are controlled by fast intramolecular vibrational energy redistribution (IVR). This fundamental ultrafast process limits coherence time in applications from photochemistry to single quantum level control. While time-resolved multidimensional IR-spectroscopy can resolve the underlying vibrational interaction dynamics, as a nonlinear optical technique it has been challenging to extend its sensitivity to probe small molecular ensembles, achieve nanoscale spatial resolution, and control intramolecular dynamics. Here, we demonstrate a concept how mode-selective coupling of vibrational resonances to IR nanoantennas can reveal intramolecular vibrational energy transfer. In time-resolved infrared vibrational nanospectroscopy, we measure the Purcell-enhanced decrease of vibrational lifetimes of molecular vibrations while tuning the IR nanoantenna across coupled vibrations. At the example of a Re-carbonyl complex monolayer, we derive an IVR rate of (25±8) cm-1 corresponding to (450±150) fs, as is typical for the fast initial equilibration between symmetric and antisymmetric carbonyl vibrations. We model the enhancement of the cross-vibrational relaxation based on intrinsic intramolecular coupling and extrinsic antenna-enhanced vibrational energy relaxation. The model further suggests an anti-Purcell effect based on antenna and laser-field-driven vibrational mode interference which can counteract IVR-induced relaxation. Nanooptical spectroscopy of antenna-coupled vibrational dynamics thus provides for an approach to probe intramolecular vibrational dynamics with a perspective for vibrational coherent control of small molecular ensembles.

Vibrational Coupling Infrared Nanocrystallography.

Coupling between molecular vibrations leads to collective vibrational states with spectral features sensitive to local molecular order. This provides spectroscopic access to the low-frequency intermolecular energy landscape. In its nanospectroscopic implementation, this technique of vibrational coupling nanocrystallography (VCNC) offers information on molecular disorder and domain formation with nanometer spatial resolution. However, deriving local molecular order relies on prior knowledge of the transition dipole magnitude and crystal structure of the underlying ordered phase. Here we develop a quantitative model for VCNC by relating nano-FTIR collective vibrational spectra to the molecular crystal structure from X-ray crystallography. We experimentally validate our approach at the example of a metal organic porphyrin complex with a carbonyl ligand as the probe vibration. This framework establishes VCNC as a powerful tool for measuring low-energy molecular interactions, wave function delocalization, nanoscale disorder, and domain formation in a wide range of molecular systems.

Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. METHODS: We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. RESULTS: Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P=0.03 versus cTnT), and 43 of 57 ([75%] P<0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] P<0.001) on admission was confirmed in 87 independent cases from an international registry. In the Franco-German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2-16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2-38.0]; P<0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients (P<0.001), respectively. CONCLUSIONS: cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.

Increased expression of human endogenous retrovirus K in endomyocardial biopsies from patients with cardiomyopathy - a transcriptomics meta-analysis.

Most studied, investigating transcriptional changes in myocardial biopsies focus on human genes. However, the presence and potential consequence of persistent expression of viral genes within the myocardium is unclear. The aim of the study was to analyze viral gene expression in RNAseq data from endomyocardial biopsies. The NCBI Bioproject library was screened for published projects that included bulk RNA sequencing data from endomyocardial biopsies from both healthy and diseased patients with a sample size greater than 20. Diseased patients with hypertrophic, dilated, and ischemic cardiomyopathies were included. A total of 507 patients with 507 samples from 6 bioprojects were included and mapped to the human genome (hg38). Unmappable sequences were extracted and mapped to an artificial 'super-virus' genome comprising 12,182 curated viral reference genomes. Subsequently, the sequences were reiteratively permutated and mapped again to account for randomness. In total, sequences from 68 distinct viruses were found, all of which were potentially human pathogenic. No increase in cardiotropic viruses was found in patients with dilated cardiomyopathy. However, the expression levels of the particle forming human endogenous retrovirus K were significantly increased (q < 0.0003, ANOVA). Higher expression levels were associated with increased expression in mitochondrial pathways such as oxidative phosphorylation (p < 0.0001). In Conclusion, expression of human endogenous retrovirus K is significantly increased in patients with dilated cardiomyopathy, which in turn was associated with transcriptional alterations in major cellular pathways.

Controlling Drug Partitioning in Individual Protein Condensates through Laser-Induced Microscale Phase Transitions.

Gelation of protein condensates formed by liquid-liquid phase separation occurs in a wide range of biological contexts, from the assembly of biomaterials to the formation of fibrillar aggregates, and is therefore of interest for biomedical applications. Soluble-to-gel (sol-gel) transitions are controlled through macroscopic processes such as changes in temperature or buffer composition, resulting in bulk conversion of liquid droplets into microgels within minutes to hours. Using microscopy and mass spectrometry, we show that condensates of an engineered mini-spidroin (NT2repCTYF) undergo a spontaneous sol-gel transition resulting in the loss of exchange of proteins between the soluble and the condensed phase. This feature enables us to specifically trap a silk-domain-tagged target protein in the spidroin microgels. Surprisingly, laser pulses trigger near-instant gelation. By loading the condensates with fluorescent dyes or drugs, we can control the wavelength at which gelation is triggered. Fluorescence microscopy reveals that laser-induced gelation significantly further increases the partitioning of the fluorescent molecules into the condensates. In summary, our findings demonstrate direct control of phase transitions in individual condensates, opening new avenues for functional and structural characterization.

Nonlinear Nano-Imaging of Interlayer Coupling in 2D Graphene-Semiconductor Heterostructures.

The emergent electronic, spin, and other quantum properties of 2D heterostructures of graphene and transition metal dichalcogenides are controlled by the underlying interlayer coupling and associated charge and energy transfer dynamics. However, these processes are sensitive to interlayer distance and crystallographic orientation, which are in turn affected by defects, grain boundaries, or other nanoscale heterogeneities. This obfuscates the distinction between interlayer charge and energy transfer. Here, nanoscale imaging in coherent four-wave mixing (FWM) and incoherent two-photon photoluminescence (2PPL) is combined with a tip distance-dependent coupled rate equation model to resolve the underlying intra- and inter-layer dynamics while avoiding the influence of structural heterogeneities in mono- to multi-layer graphene/WSe2 heterostructures. With selective insertion of hBN spacer layers, it is shown that energy, as opposed to charge transfer, dominates the interlayer-coupled optical response. From the distinct nano-FWM and -2PPL tip-sample distance-dependent modification of interlayer and intralayer relaxation by tip-induced enhancement and quenching, an interlayer energy transfer time of τ ET ≈ ( 0 . 35 - 0.15 + 0.65 ) $\tau _{\rm ET} \approx (0.35^{+0.65}_{-0.15})$  ps consistent with recent reports is derived. As a local probe technique, this approach highlights the ability to determine intrinsic sample properties even in the presence of large sample heterogeneity.

Triblock Proteins with Weakly Dimerizing Terminal Blocks and an Intrinsically Disordered Region for Rational Design of Condensate Properties.

Condensates are molecular assemblies that are formed through liquid-liquid phase separation and play important roles in many biological processes. The rational design of condensate formation and their properties is central to applications, such as biosynthetic materials, synthetic biology, and for understanding cell biology. Protein engineering is used to make a triblock structure with varying terminal blocks of folded proteins on both sides of an intrinsically disordered mid-region. Dissociation constants are determined in the range of micromolar to millimolar for a set of proteins suitable for use as terminal blocks. Varying the weak dimerization of terminal blocks leads to an adjustable tendency for condensate formation while keeping the intrinsically disordered region constant. The dissociation constants of the terminal domains correlate directly with the tendency to undergo liquid-liquid phase separation. Differences in physical properties, such as diffusion rate are not directly correlated with the strength of dimerization but can be understood from the properties and interplay of the constituent blocks. The work demonstrates the importance of weak interactions in condensate formation and shows a principle for protein design that will help in fabricating functional condensates in a predictable and rational way.

Trends in Incidence and Outcomes of Cardiac Arrest Occurring in Swedish ICUs.

OBJECTIVE: To determine temporal trends in the incidence of cardiac arrest occurring in the ICU (ICU-CA) and its associated long-term mortality. DESIGN: Retrospective observational study. SETTING: Swedish ICUs, between 2011 and 2017. PATIENTS: Adult patients (≥18 yr old) recorded in the Swedish Intensive Care Registry (SIR). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU-CA was defined as a first episode of cardiopulmonary resuscitation and/or defibrillation following an ICU admission, as recorded in SIR or the Swedish Cardiopulmonary Resuscitation Registry. Annual adjusted ICU-CA incidence trend (all admissions) was estimated using propensity score-weighted analysis. Six-month mortality trends (first admissions) were assessed using multivariable mixed-effects logistic regression. Analyses were adjusted for pre-admission characteristics (sex, age, socioeconomic status, comorbidities, medications, and healthcare utilization), illness severity on ICU admission, and admitting unit. We included 231,427 adult ICU admissions. Crude ICU-CA incidence was 16.1 per 1,000 admissions, with no significant annual trend in the propensity score-weighted analysis. Among 186,530 first admissions, crude 6-month mortality in ICU-CA patients was 74.7% (95% CI, 70.1-78.9) in 2011 and 68.8% (95% CI, 64.4-73.0) in 2017. When controlling for multiple potential confounders, the adjusted 6-month mortality odds of ICU-CA patients decreased by 6% per year (95% CI, 2-10). Patients admitted after out-of-hospital or in-hospital cardiac arrest had the highest ICU-CA incidence (136.1/1,000) and subsequent 6-month mortality (76.0% [95% CI, 73.6-78.4]). CONCLUSIONS: In our nationwide Swedish cohort, the adjusted incidence of ICU-CA remained unchanged between 2011 and 2017. More than two-thirds of patients with ICU-CA did not survive to 6 months following admission, but a slight improvement appears to have occurred over time.

Universal Definition of the Nonconformal Trace Anomaly.

We show that there exists a generalized, universal notion of the trace anomaly for theories which are not conformally invariant at the classical level. The definition is suitable for any regularization scheme and clearly states to what extent the classical equations of motion should be used, thus resolving existing controversies surrounding previous proposals. Additionally, we exhibit the link between our definition of the anomaly and the functional Jacobian arising from a Weyl transformation.

Electrically Tunable Single Polaritonic Quantum Dot at Room Temperature.

Exciton-polaritons confined in plasmonic cavities are hybridized light-matter quasiparticles, with distinct optical characteristics compared to plasmons and excitons alone. Here, we demonstrate the electric tunability of a single polaritonic quantum dot operating at room temperature in electric-field tip-enhanced strong coupling spectroscopy. For a single quantum dot in the nanoplasmonic tip cavity with variable dc local electric field, we dynamically control the Rabi frequency with the corresponding polariton emission, crossing weak to strong coupling. We model the observed behaviors based on the quantum confined Stark effect in the strong coupling regime.

Effect of Phosphate on the Molecular Properties, Interactions, and Assembly of Engineered Spider Silk Proteins.

Phosphate plays a vital role in spider silk spinning and has been utilized in numerous artificial silk spinning attempts to replicate the remarkable mechanical properties of natural silk fiber. Its application in artificial processes has, however, yielded varying outcomes. It is thus necessary to investigate the origins and mechanisms behind these differences. By using recombinant silk protein SC-ADF3 derived from the garden spider Araneus diadematus, here, we describe its conformational changes under various conditions, elucidating the effect of phosphate on SC-ADF3 silk protein properties and interactions. Our results demonstrate that elevated phosphate levels induce the irreversible conformational conversion of SC-ADF3 from random coils to ß-sheet structures, leading to decreased protein solubility over time. Furthermore, exposure of SC-ADF3 to phosphate stiffens already formed structures and reduces the ability to form new interactions. Our findings offer insights into the underlying mechanism through which phosphate-induced ß-sheet structures in ADF3-related silk proteins impede fiber formation in the subsequent phases. From a broader perspective, our studies emphasize the significance of silk protein conformation for functional material formation, highlighting that the formation of ß-sheet structures at the initial stages of protein assembly will affect the outcome of material forming processes.

A national surveillance system for continuous monitoring of blood transfusion safety: German haemovigilance data.

BACKGROUND AND OBJECTIVES: Haemovigilance (HV) systems aim to improve transfusion outcomes in patients and donor safety. An important question for blood regulators is how to ensure an effective HV system. MATERIALS AND METHODS: We retrospectively analysed the HV reports submitted to Paul-Ehrlich-Institut over the last two decades. RESULTS: Between 2011 and 2020, 50.86 million units of blood components were used, and 8931 suspected serious donor and recipient adverse reactions (SARs), 874 serious adverse events (SAEs) and 12,073 donor look-backs were reported. Following implementation of specific risk-minimization measures (RMMs) between 2000 and 2010, SAR reporting rates decreased for transfusion-transmitted viral infections (TTVIs), transfusion-related acute lung injury (TRALI) and transfusion-transmitted bacterial infections (TTBIs), while increasing for other serious adverse transfusion reactions. Within this decade, the overall blood component use decreased. CONCLUSION: Long-term data collection forms the basis to establish trends and changes in reporting and to evaluate the effect of RMM. Standardized criteria for reaction types, seriousness and imputability assessments and availability of a denominator are important elements. Central data collection and independent assessment allow for monitoring HV data in a nationwide context over time. Stakeholder involvement and transparent feedback on the benefit of RMM will help to achieve the objectives of HV.

Factors associated with fever after cardiac arrest: A post-hoc analysis of the FINNRESUSCI study.

BACKGROUND: Fever after cardiac arrest may impact outcome. We aimed to assess the incidence of fever in post-cardiac arrest patients, factors predicting fever and its association with functional outcome in patients treated without targeted temperature management (TTM). METHODS: The FINNRESUSCI observational cohort study in 2010-2011 included intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients from all five Finnish university hospitals and 14 of 15 central hospitals. This post hoc analysis included those FINNRESUSCI study patients who were not treated with TH. We defined fever as at least one temperature measurement of ≥37.8°C within 72 h of ICU admission. The primary outcome was favourable functional outcome at 12 months, defined as cerebral performance category (CPC) of 1 or 2. Binary logistic regression models including witnessed arrest, bystander cardiopulmonary resuscitation (CPR), initial rhythm and delay of return of spontaneous circulation were used to compare the functional outcomes of the groups. RESULTS: There were 67,428 temperature measurements from 192 patients, of whom 89 (46%) experienced fever. Twelve-month CPC was missing in 7 patients, and 51 (28%) patients had favourable functional outcome at 12 months. The patients with shockable initial rhythms had a lower incidence of fever within 72 h of ICU admission (28% vs. 72%, p < .01), and the patients who experienced fever had a longer median return of spontaneous circulation (ROSC) delay (20 [IQR 10-30] vs. 14 [IQR 9-22] min, p < .01). Only initial non-shockable rhythm (OR 2.99, 95% CI 1.51-5.94) was associated with increased risk of fever within the first 72 h of ICU admission. Neither time in minutes nor area (minutes × degree celsius over threshold) over 37°C, 37.5°C, 38°C, 38.5°C, 39°C, 39.5°C or 40°C were significantly different in those with favourable functional outcome compared to those with unfavourable functional outcome within the first 24, 48 or 72 h from ICU admission. Fever was not associated with favourable functional outcome at 12 months (OR 0.90, 95% CI 0.44-1.84). CONCLUSIONS: Half of OHCA patients not treated with TTM developed fever. We found no association between fever and outcome.

Tip-Enhanced Dark Exciton Nanoimaging and Local Strain Control in Monolayer WSe2.

Dark excitons in transition-metal dichalcogenides, with their long lifetimes and strong binding energies, provide potential platforms from photonic and optoelectronic applications to quantum information science even at room temperature. However, their spatial heterogeneity and sensitivity to strain is not yet understood. Here, we combine tip-enhanced photoluminescence spectroscopy with atomic force induced strain control to nanoimage dark excitons in WSe2 and their response to local strain. Dark exciton emission is facilitated by out-of-plane picocavity Purcell enhancement giving rise to spatially highly localized emission, providing for higher spatial resolution compared to bright exciton nanoimaging. Further, tip-antenna-induced dark exciton emission is enhanced in areas of higher strain associated with bubbles. In addition, active force control shows dark exciton emission to be more sensitive to strain with both compressive and tensile lattice deformation facilitating emission. This interplay between localized strain and Purcell effects provides novel pathways for nanomechanical exciton emission control.

Ultrafast Nanoimaging of Electronic Coherence of Monolayer WSe2.

Transition-metal dichalcogenides (TMDs) have demonstrated a wide range of novel photonic, optoelectronic, and correlated electron phenomena for more than a decade. However, the coherent dynamics of their excitons, including possibly long dephasing times and their sensitivity to spatial heterogeneities, are still poorly understood. Here we implement adiabatic plasmonic nanofocused four-wave mixing (FWM) to image the coherent electron dynamics in monolayer WSe2. We observe nanoscale heterogeneities at room temperature with dephasing ranging from T2 ≲ 5 to T2 ≳ 60 fs on length scales of 50-100 nm. We further observe a counterintuitive anticorrelation between FWM intensity and T2, with the weakest FWM emission at locations of longest coherence. We interpret this behavior as a nonlocal nano-optical interplay between spatial coherence of the nonlinear polarization and disorder-induced scattering. The results highlight the challenges associated with heterogeneities in TMDs limiting their photophysical properties, yet also the potential of their novel nonlinear optical phenomena.

Gate-Tuning Hybrid Polaritons in Twisted α-MoO3/Graphene Heterostructures.

Modulating anisotropic phonon polaritons (PhPs) can open new avenues in infrared nanophotonics. Promising PhP dispersion engineering through polariton hybridization has been demonstrated by coupling gated graphene to single-layer α-MoO3. However, the mechanism underlying the gate-dependent modulation of hybridization has remained elusive. Here, using IR nanospectroscopic imaging, we demonstrate active modulation of the optical response function, quantified in measurements of gate dependence of wavelength, amplitude, and dissipation rate of the hybrid plasmon-phonon polaritons (HPPPs) in both single-layer and twisted bilayer α-MoO3/graphene heterostructures. Intriguingly, while graphene doping leads to a monotonic increase in HPPP wavelength, amplitude and dissipation rate show transition from an initially anticorrelated decrease to a correlated increase. We attribute this behavior to the intricate interplay of gate-dependent components of the HPPP complex momentum. Our results provide the foundation for active polariton control of integrated α-MoO3 nanophotonics devices.