Elucidating the mechanisms and efficacy of antimalarial drugs in systemic lupus erythematosus.

INTRODUCTION: Antimalarials (AMs) are old drugs with a wide range of beneficial effects in systemic lupus erythematosus (SLE) beyond the control of activity. The most recent debate is focused on defining the optimal doses to assure the best benefit/risk ratio. AREAS COVERED: We have reviewed the pharmacological basis underlying the various therapeutic effects of AMs and the beneficial and toxic effects of HCQ, also discussing the role of mepacrine not only as a substitute in cases of maculopathy, but also as a very effective therapy combined with HCQ. We searched PubMed and Embase for articles published in English at any time. We used the terms "hydroxychloroquine" or "mepacrine" or "chloroquine" or "antimalarials", "pharmacokinetics", "efficacy", "remission", "toxicity", "adherence". We reviewed original research articles, large observational studies, systematic reviews, and expert consensus statements. Additionally, studies were identified through the assessment of the reference lists of the evaluated manuscripts. EXPERT OPINION: We advocate for the widespread use of HCQ at stable doses of 200 mg/d (≤4 mg/kg/d for most patients) and also for the early combination therapy with mepacrine to assure a good control of SLE activity, and also a durable and safe use of these essential drugs for the management of SLE.

Use of Glucocorticoids in SLE: A Clinical Approach.

Glucocorticoids (GCs) are one of the most effective first-line treatments for systemic lupus erythematosus (SLE). However, GC burden is associated with damage. The initial GC dose and tapering schedule should be tailored to the severity of the clinical scenario. As lupus therapy should prompt remission while minimising damage, recent guidelines recommend a more accurate approach to the use of GCs, setting lower starting doses and rapid tapering schemes, and encouraging maintenance prednisolone doses <5 mg/day. Methylprednisolone pulses (MP) help to reduce the dose of oral GCs and improve the clinical response in both severe and non-severe manifestations, without significant side effects. Fixed-tapering GC scheme provides a useful strategy to reduce GCs exposure. Long-term antimalarial treatment and early initiation of immunosuppressive drugs improve clinical efficacy while reducing GC toxicity. Besides, withdrawal of GCs is an achievable goal in patients in prolonged remission on stable treatment, and recent studies have attempted to identify the most suitable candidates. In this article, we review the pharmacological basis, clinical evidence of efficacy, dose-related harms, and potential withdrawal of GCs. We also review guidelines recommendations and finally give a personal and practical approach to dealing with the use of GCs in SLE patients.

Thrombotic antiphospholipid syndrome: From guidelines to clinical management.

Thrombotic manifestations, mainly venous thromboembolism (VTE) and stroke, are the most common and potentially life-threatening presentations of antiphospholipid syndrome (APS). The management of APS requires the assessment of the antiphospholipid antibodies (aPL) profile, of concurrent systemic lupus erythematosus or other systemic autoimmune diseases and the presence of risk factors for cardiovascular disease and bleeding. Anticoagulation with vitamin K antagonists (VKA) remains the cornerstone of therapy for thrombotic APS. As platelets play a central role in APS, low-dose aspirin is the first option for primary thromboprophylaxis in asymptomatic aPL carriers, and also plays a role as combination therapy with VKAs in arterial thrombosis. Treatment with direct oral anticoagulants (DOACs) could be considered in certain low-risk situations, although they are not recommended in patients with arterial thrombosis or triple positive aPL. Adjuvant therapies such as hydroxychloroquine and statins may be useful in complex settings such as thrombotic recurrences or high risk of bleeding. In this article, we review the evidence and the recommendations of the guidelines for the treatment of APS, and provide a critical and practical approach of its management from our clinical perspective.

Routine biomarker profile for the prediction of clinical phenotypes of adult-onset Still's disease using unsupervised clustering algorithm.

AIM: This study addresses the challenge of predicting the course of Adult-onset Still's disease (AoSD), a rare systemic autoinflammatory disorder of unknown origin. Precise prediction is crucial for effective clinical management, especially in the absence of specific laboratory indicators. METHODS: We assessed the effectiveness of combining traditional biomarkers with the k-medoids unsupervised clustering algorithm in forecasting the various clinical courses of AoSD-monocyclic, polycyclic, or chronic articular. This approach represents an innovative strategy in predicting the disease's course. RESULTS: The analysis led to the identification of distinct patient profiles based on accessible biomarkers. Specifically, patients with elevated ferritin levels at diagnosis were more likely to experience a monocyclic disease course, while those with lower erythrocyte sedimentation rate could present with any of the clinical courses, monocyclic, polycyclic, or chronic articular, during follow-up. CONCLUSION: The study demonstrates the potential of integrating traditional biomarkers with unsupervised clustering algorithms in understanding the heterogeneity of AoSD. These findings suggest new avenues for developing personalized treatment strategies, though further validation in larger, prospective studies is necessary.

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective.

Two-dimensional (2D) materials have attracted tremendous interest ever since the isolation of atomically thin sheets of graphene in 2004 due to the specific and versatile properties of these materials. However, the increasing production and use of 2D materials necessitate a thorough evaluation of the potential impact on human health and the environment. Furthermore, harmonized test protocols are needed with which to assess the safety of 2D materials. The Graphene Flagship project (2013-2023), funded by the European Commission, addressed the identification of the possible hazard of graphene-based materials as well as emerging 2D materials including transition metal dichalcogenides, hexagonal boron nitride, and others. Additionally, so-called green chemistry approaches were explored to achieve the goal of a safe and sustainable production and use of this fascinating family of nanomaterials. The present review provides a compact survey of the findings and the lessons learned in the Graphene Flagship.

Balancing risks and benefits in the use of hydroxychloroquine and glucocorticoids in systemic lupus erythematosus.

INTRODUCTION: Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly regarding the dose. AREAS COVERED: We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence. EXPERT OPINION: HCQ is the backbone therapy for SLE, and a judicious use must be accomplished, using doses that allow a good control of lupus without compromising the safety of treatments very much prolonged over the time. Stable doses of 200 mg/day seem to accomplish both conditions. GCs should be used more judiciously, with methyl-prednisolone pulses as the main therapy for inducing rapid remission and doses ≤5-2.5 mg/day be never exceeded in long-term maintenance treatments.

Eye State Detection Using Frequency Features from 1 or 2-Channel EEG.

Brain-computer interfaces (BCIs) establish a direct communication channel between the human brain and external devices. Among various methods, electroencephalography (EEG) stands out as the most popular choice for BCI design due to its non-invasiveness, ease of use, and cost-effectiveness. This paper aims to present and compare the accuracy and robustness of an EEG system employing one or two channels. We present both hardware and algorithms for the detection of open and closed eyes. Firstly, we utilize a low-cost hardware device to capture EEG activity from one or two channels. Next, we apply the discrete Fourier transform to analyze the signals in the frequency domain, extracting features from each channel. For classification, we test various well-known techniques, including Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), Decision Tree (DT), or Logistic Regression (LR). To evaluate the system, we conduct experiments, acquiring signals associated with open and closed eyes, and compare the performance between one and two channels. The results demonstrate that employing a system with two channels and using SVM, DT, or LR classifiers enhances robustness compared to a single-channel setup and allows us to achieve an accuracy percentage greater than 95% for both eye states.

Nanocomposite Hydrogels with Self-Assembling Peptide-Functionalized Carbon Nanostructures.

Carbon nanostructures (CNSs) are attractive components to attain nanocomposites, yet their hydrophobic nature and strong tendency to aggregate often limit their use in aqueous conditions and negatively impact their properties. In this work, carbon nanohorns (CNHs), multi-walled carbon nanotubes (CNTs), and graphene (G) are first oxidized, and then reacted to covalently anchor the self-assembling tripeptide L-Leu-D-Phe-D-Phe to improve their dispersibility in phosphate buffer, and favor the formation of hydrogels formed by the self-organizing L-Leu-D-Phe-D-Phe present in solution. The obtained nanocomposites are then characterized by transmission electron microscopy (TEM), oscillatory rheology, and conductivity measurements to gain useful insights as to the key factors that determine self-healing ability for the future design of this type of nanocomposites.

Understanding the Raman enhancement of carbon nanohorns labelled with organic dyes.

Carbon nanohorns have been non-covalently functionalized with two different benzothiadiazoloquinoxalines prepared via Stille cross-coupling reactions under solvent-free conditions and microwave irradiation. The close interactions between these organic molecules and the nanostructures resulted in a prominent Raman enhancement, which makes them attractive candidates for multiple applications. A complete experimental physico-chemical characterization has been combined with in silico studies to understand these phenomena. The processability of the hybrids was exploited to prepare homogeneous films on substrates with different natures.

Intravenous cyclophosphamide improves functional outcomes in interstitial lung disease related to idiopathic inflammatory myopathies.

OBJECTIVE: To compare the efficacy, toxicity and glucocorticoid (GC)-sparing effects of intravenous cyclophosphamide (iv CYC) with other immunosuppressive regimes as the induction treatment for Idiopathic Inflammatory Myopathy-Related Interstitial Lung Disease (IIM-ILD). METHODS: Observational comparative study of patients with IIM-ILD from the EPIMAR and Cruces cohorts. The main efficacy outcome was a 6 to 12-month improvement >10% in the forced vital capacity (FVC) from baseline. RESULTS: Overall, 47 patients were included: 22 (47%) in the CYC group and 25 (53%) in the non-CYC group (32% azathioprine, 28% GC alone, 20% mycophenolate, 16% calcineurin-inhibitors and methotrexate and 4% rituximab). 81% patients were female with a mean age of 50.4 years. FVC improvement was achieved by 64% patients in the CYC group vs. 32% in the non-CYC group (p = 0.03). In the logistic regression model, CYC was identified as the only independent predictor of FVC improvement (OR=3.97, 95% CI 1.07-14.75). Patients in the CYC group received more methyl-prednisolone pulses (MP) (59% vs. 28% in the non-CYC group, p = 0.03), less initial GCs doses >30 mg/d (19% vs. 77%, p = 0.001) and lower 6-month average doses of prednisone (11 mg/d vs. 31.1 mg/d, p = 0.001). CONCLUSION: iv CYC showed better functional outcomes than other immunosuppressants in IIM-ILD. The additional use of MP is likely to potentiate the effects of CYC and allows lowering prednisone doses. Therefore, CYC in combination with MP could be considered as the first line induction therapy in IIM-ILD, without limiting its use to rapidly progressive, life-threatening or refractory disease.

Distinct spectral dynamics of implanted cardiac defibrillator signals in spontaneous termination of polymorphic ventricular tachycardia and fibrillation in patients with electrical and structural diseases.

AIMS: To determine the spectral dynamics of early spontaneous polymorphic ventricular tachycardia and ventricular fibrillation (PVT/VF) in humans. METHODS AND RESULTS: Fifty-eight self-terminated and 173 shock-terminated episodes of spontaneously initiated PVT/VF recorded by Medtronic implanted cardiac defibrillators (ICDs) in 87 patients with various cardiac pathologies were analyzed by short fast Fourier transform of shifting segments to determine the dynamics of dominant frequency (DF) and regularity index (RI). The progression in the intensity of DF and RI accumulations further quantified the time course of spectral characteristics of the episodes. Episodes of self-terminated PVT/VF lasted 8.6 s [95% confidence interval (CI): 8.1-9.1] and shock-terminated lasted 13.9 s (13.6-14.3) (P < 0.001). Recordings from patients with primarily electrical pathologies displayed higher DF and RI values than those from patients with primarily structural pathologies (P < 0.05) independently of ventricular function or antiarrhythmic drug therapy. Regardless of the underlying pathology, the average DF and RI intensities were lower in self-terminated than shock-terminated episodes [DF: 3.67 (4.04-4.58) vs. 4.32 (3.46-3.93) Hz, P < 0.001; RI: 0.53 (0.48-0.56) vs. 0.63 (0.60-0.65), P < 0.001]. In a multivariate analysis controlled by the type of pathology and clinical variables, regularity remained an independent predictor of self-termination [hazard ratio: 0.954 (0.928-0.980)]. Receiver operating characteristic (ROC) curve analysis of DF and RI intensities demonstrated increased predictability for self-termination in time with 95% CI above the 0.5 cut-off limit at about t = 8.6 s and t = 6.95 s, respectively. CONCLUSION: Consistent with the notion that fast organized sources maintain PVT/VF in humans, reduction of frequency and regularity correlates with early self-termination. Our findings might help generate ICD methods aiming to reduce inappropriate shock deliveries.

Panoramic Endocardial Optical Mapping Demonstrates Serial Rotors Acceleration and Increasing Complexity of Activity During Onset of Cholinergic Atrial Fibrillation.

Background Activation during onset of atrial fibrillation is poorly understood. We aimed at developing a panoramic optical mapping system for the atria and test the hypothesis that sequential rotors underlie acceleration of atrial fibrillation during onset. Methods and Results Five sheep hearts were Langendorff perfused in the presence of 0.25 µmol/L carbachol. Novel optical system recorded activations simultaneously from the entire left and right atrial endocardial surfaces. Twenty sustained (>40 s) atrial fibrillation episodes were induced by a train and premature stimuli protocol. Movies obtained immediately (Initiation stage) and 30 s (Early Stabilization stage) after premature stimulus were analyzed. Serial rotor formation was observed in all sustained inductions and none in nonsustained inductions. In sustained episodes maximal dominant frequency increased from (mean±SD) 11.5±1.74 Hz during Initiation to 14.79±1.30 Hz at Early Stabilization (P<0.0001) and stabilized thereafter. At rotor sites, mean cycle length (CL) during 10 prerotor activations increased every cycle by 0.53% (P=0.0303) during Initiation and 0.34% (P=0.0003) during Early Stabilization. In contrast, CLs at rotor sites showed abrupt decreases after the rotors appearances by a mean of 9.65% (P<0.0001) during both stages. At Initiation, atria-wide accelerations and decelerations during rotors showed a net acceleration result whereby post-rotors atria-wide minimal CL (CLmin) were 95.5±6.8% of the prerotor CLmin (P=0.0042). In contrast, during Early Stabilization, there was no net acceleration in CLmin during accelerating rotors (prerotor=84.9±11.0% versus postrotor=85.8±10.8% of Initiation, P=0.4029). Levels of rotor drift distance and velocity correlated with atria-wide acceleration. Nonrotor phase singularity points did not accelerate atria-wide activation but multiplied during Initiation until Early Stabilization. Increasing number of singularity points, indicating increased complexity, correlated with atria-wide CLmin reduction (P<0.0001). Conclusions Novel panoramic optical mapping of the atria demonstrates shortening CL at rotor sites during cholinergic atrial fibrillation onset. Atrial fibrillation acceleration toward Early Stabilization correlates with the net result of atria-wide accelerations during drifting rotors activity.

Light-Programmable Logic-in-Memory in 2D Semiconductors Enabled by Supramolecular Functionalization: Photoresponsive Collective Effect of Aligned Molecular Dipoles.

Nowadays, the unrelenting growth of the digital universe calls for radically novel strategies for data processing and storage. An extremely promising and powerful approach relies on the development of logic-in-memory (LiM) devices through the use of floating gate and ferroelectric technologies to write and erase data in a memory operating as a logic gate driven by electrical bias. In this work, we report an alternative approach to realize the logic-in-memory based on two-dimensional (2D) transition metal dichalcogenides (TMDs) where multiple memorized logic output states have been established via the interface with responsive molecular dipoles arranged in supramolecular arrays. The collective dynamic molecular dipole changes of the axial ligand coordinated onto self-assembled metal phthalocyanine nanostructures on the surface of 2D TMD enables large reversible modulation of the Fermi level of both n-type molybdenum disulfide (MoS2) and p-type tungsten diselenide (WSe2) field-effect transistors (FETs), to achieve multiple memory states by programming and erasing with ultraviolet (UV) and with visible light, respectively. As a result, logic-in-memory devices were built up with our supramolecular layer/2D TMD architecture where the output logic is encoded by the motion of the molecular dipoles. Our strategy relying on the dynamic control of the 2D electronics by harnessing the functions of molecular-dipole-induced memory in a supramolecular hybrid layer represents a versatile way to integrate the functional programmability of molecular science into the next generation nanoelectronics.

Anti-phospholipid antibodies do not predict damage in SLE patients in the 21st century-an observational study from the Lupus-Cruces cohort.

OBJECTIVE: To compare the influence of aPLs on global and cardiovascular damage in patients with SLE diagnosed before and after the year 2000. METHODS: Two hundred and eighty-six patients from the Lupus-Cruces cohort with a minimum follow-up of 5 years were divided into two subcohorts according to the date of diagnosis, before 2000 (less than 2000) and from 2000 on (2000 or more). We compared the mean Systemic Lupus Erythematosus International Collaborating Clinics-American College of Rheumatology (SLICC-ACR) Damage Index score and global and cardiovascular damage-free survival rates in the presence or absence of aPL in both subcohorts. Variables potentially modulating damage among aPL-positive patients were analysed. RESULTS: The subcohorts were comparable for demographic and lupus-related variables except for treatment variables: the 2000 or more subcohort received lower doses of prednisone and more HCQ, low-dose aspirin, statins, immunosuppressive agents and vitamin D. aPL-positive patients in the less than 2000, but not in the 2000 or more subcohort, accrued more damage compared with aPL-negative patients. In the less than 2000 subcohort, the adjusted hazard ratios (HRs) for global and cardiovascular damage in aPL-positive vs aPL-negative patients were 1.98 (95% CI 1.24, 3.14) and 9.3 (95% CI 3.24, 26.92), respectively. No differences in damage were seen between aPL-positive and aPL-negative patients in the 2000 or more subcohort. Hypertension (HR = 4.64, 95% CI 1.33, 16.19), LA (HR = 3.85, 95% CI 1.1, 13.41) and the number of months on HCQ (HR = 0.97, 95% CI 0.95, 0.99) were independent predictors of vascular damage in the combined analysis of all aPL-positive patients. CONCLUSION: The effects of aPL on damage accrual in SLE patients have been reduced over recent years. The widespread use of HCQ and a better thromboprophylaxis are likely causing this change.

Graphene: A Disruptive Opportunity for COVID-19 and Future Pandemics?

The graphene revolution, which has taken place during the last 15 years, has represented a paradigm shift for science. The extraordinary properties possessed by this unique material have paved the road to a number of applications in materials science, optoelectronics, energy, and sensing. Graphene-related materials (GRMs) are now produced in large scale and have found niche applications also in the biomedical technologies, defining new standards for drug delivery and biosensing. Such advances position GRMs as novel tools to fight against the current COVID-19 and future pandemics. In this regard, GRMs can play a major role in sensing, as an active component in antiviral surfaces or in virucidal formulations. Herein, the most promising strategies reported in the literature on the use of GRM-based materials against the COVID-19 pandemic and other types of viruses are showcased, with a strong focus on the impact of functionalization, deposition techniques, and integration into devices and surface coatings.

Burn-out syndrome in Spanish internists during the COVID-19 outbreak and associated factors: a cross-sectional survey.

OBJECTIVES: The objective of this study is to evaluate the impact of the COVID-19 outbreak on mental health and burn-out syndrome in Spanish internists and the factors that could be related to its appearance. DESIGN: We performed an observational, cross-sectional, descriptive study for which we designed a survey that was distributed in May 2020. SETTING: We included internists who worked in Spain during the COVID-19 outbreak. PARTICIPANTS: A total of 1015 internists responded to the survey. Of those 62.9% were women. RESULTS: Of 1015 people, 58.3% presented with high emotional exhaustion, 61.5% had a high level of depersonalisation and 67.6% reported low personal fulfilment. 40.1% presented with the 3 criteria described, and therefore burn-out syndrome.Burn-out syndrome was independently related to the management of patients with SARS-CoV-2 (HR: 2.26; 95% CI 1.15 to 4.45), the lack of availability of personal protective equipment (HR: 1.41; 95% CI 1.05 to 1.91), increased responsibility (HR: 2.13; 95% CI 1.51 to 3.01), not having received financial compensation for overtime work (HR: 0.43; 95% CI 0.31 to 0.62), not having rested after 24-hour shifts (HR: 1.61; 95% CI 1.09 to 2.38), not having had holidays in the previous 6 months (HR: 1.36; 95% CI 1.01 to 1.84), consumption of sleeping pills (HR: 1.83; 95% CI 1.28 to 2.63) and higher alcohol intake (HR: 1.95; 95% CI 1.39 to 2.73). CONCLUSIONS: During the COVID-19 outbreak, 40.1% of Internal Medicine physicians in Spain presented with burn-out syndrome, which was independently related to the assistance of patients with SARS-CoV-2, overworking without any compensation and the fear of being contagious to their relatives. Therefore, it is imperative to initiate programmes to prevent and treat burn-out in front-line physicians during the COVID-19 outbreak.

NT-proBNP levels in preeclampsia, intrauterine growth restriction as well as in the prediction on an imminent delivery.

OBJECTIVES: Studies of cardiovascular function in pregnancy have shown inconsistent and, in some cases, contradictory results, particularly regarding cardiac output. While some studies report preeclampsia associated with high cardiac output, other studies suggest that preeclampsia should be further subdivided into women with high or low cardiac output. This study was conducted to examine the NT-proBNP levels in preeclampsia, intrauterine growth restriction, and hypertensive pregnancies without preeclampsia. We also examined N-terminal pro-B natriuretic peptide (NT-proBNP) levels three to four months after delivery, in preeclamptic women as well as the prediction of delivery within 10 days. In a reduced number of preeclamptic women and controls we performed echocardiograms to study their diastolic function. METHODS: We investigated the NT-proBNP levels in 213 subjects with preeclampsia only, 73 with intrauterine growth restriction, 44 with preeclampsia and intrauterine growth restriction, 211 who were hypertensive and 662 unaffected pregnancies (controls). We also performed echocardiograms on 36 preeclampsia and 19 controls before delivery and three to five months after delivery. RESULTS: NT-proBNP levels are higher in early onset preeclampsia than in late onset preeclampsia. Intrauterine growth restriction pregnancies showed a NT-proBNP levels similar to hypertensive and unaffected pregnancies. Compared with healthy pregnancies, women with preterm preeclampsia (<37 gestational weeks) had altered left atrial segments. CONCLUSIONS: We observed that NT-proBNP levels are higher in early onset preeclampsia than in late onset. Moreover, diastolic dysfunction is higher in early onset than in late-onset term preeclampsia. An NT-proBNP value >136 pg/mL has a high positive predictive value for an imminent delivery within 10 days.

Nanoscale Assembly of Functional Peptides with Divergent Programming Elements.

Self-assembling peptides are being applied both in the biomedical area and as building blocks in nanotechnology. Their applications are closely linked to their modes of self-assembly, which determine the functional nanostructures that they form. This work brings together two structural elements that direct nanoscale self-association in divergent directions: proline as a ß-breaker and the ß-structure-associated diphenylalanine motif, into a single tripeptide sequence. Amino acid chirality was found to resolve the tension inherent to these conflicting self-assembly instructions. Stereoconfiguration determined the ability of each of the eight possible Pro-Phe-Phe stereoisomers to self-associate into diverse nanostructures, including nanoparticles, nanotapes, or fibrils, which yielded hydrogels with gel-to-sol transition at a physiologically relevant temperature. Three single-crystal structures and all-atom molecular dynamics simulations elucidated the ability of each peptide to establish key interactions to form long-range assemblies (i,e., stacks leading to gelling fibrils), medium-range assemblies (i.e., stacks yielding nanotapes), or short-range assemblies (i.e., dimers or trimers that further associated into nanoparticles). Importantly, diphenylalanine is known to serve as a binding site for pathological amyloids, potentially allowing these heterochiral systems to influence the fibrillization of other biologically relevant peptides. To probe this hypothesis, all eight Pro-Phe-Phe stereoisomers were tested in vitro on the Alzheimer's disease-associated Aß(1-42) peptide. Indeed, one nonfibril-forming stereoisomer effectively inhibited Aß fibrillization through multivalent binding between diphenylalanine motifs. This work thus defined heterochirality as a useful feature to strategically develop future therapeutics to interfere with pathological processes, with the additional value of resistance to protease-mediated degradation and biocompatibility.

Covalently interconnected transition metal dichalcogenide networks via defect engineering for high-performance electronic devices.

Solution-processed semiconducting transition metal dichalcogenides are at the centre of an ever-increasing research effort in printed (opto)electronics. However, device performance is limited by structural defects resulting from the exfoliation process and poor inter-flake electronic connectivity. Here, we report a new molecular strategy to boost the electrical performance of transition metal dichalcogenide-based devices via the use of dithiolated conjugated molecules, to simultaneously heal sulfur vacancies in solution-processed transition metal disulfides and covalently bridge adjacent flakes, thereby promoting percolation pathways for the charge transport. We achieve a reproducible increase by one order of magnitude in field-effect mobility (µFE), current ratio (ION/IOFF) and switching time (τS) for liquid-gated transistors, reaching 10-2 cm2 V-1 s-1, 104 and 18 ms, respectively. Our functionalization strategy is a universal route to simultaneously enhance the electronic connectivity in transition metal disulfide networks and tailor on demand their physicochemical properties according to the envisioned applications.