Chemoproteomic mapping of the glycolytic targetome in cancer cells.

Hyperactivated glycolysis is a metabolic hallmark of most cancer cells. Although sporadic information has revealed that glycolytic metabolites possess nonmetabolic functions as signaling molecules, how these metabolites interact with and functionally regulate their binding targets remains largely elusive. Here, we introduce a target-responsive accessibility profiling (TRAP) approach that measures changes in ligand binding-induced accessibility for target identification by globally labeling reactive proteinaceous lysines. With TRAP, we mapped 913 responsive target candidates and 2,487 interactions for 10 major glycolytic metabolites in a model cancer cell line. The wide targetome depicted by TRAP unveils diverse regulatory modalities of glycolytic metabolites, and these modalities involve direct perturbation of enzymes in carbohydrate metabolism, intervention of an orphan transcriptional protein's activity and modulation of targetome-level acetylation. These results further our knowledge of how glycolysis orchestrates signaling pathways in cancer cells to support their survival, and inspire exploitation of the glycolytic targetome for cancer therapy.

Discovery of a novel series of selective macrocyclic PKCTheta inhibitors.

A series of macrocyclic PKCθ inhibitors based on a 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one hinge binder has been studied. Different aromatic and heteroaromatic substituents have been explored in order to optimize potency, isoform selectivity as well as DMPK properties. The importance of the length of the macrocyclic linker has also been analyzed. In particular, it has been found that methyl substitutions on the linker can have a profound influence on both potency and metabolic stability. Several compounds showing very good profiles, suitable for in vivo testing, are disclosed.

STING inhibitors target the cyclic dinucleotide binding pocket.

Cytosolic DNA activates cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers interferon and inflammatory responses that help defend against microbial infection and cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome and constituently active gain-of-function mutations in STING in STING-associated vasculopathy with onset in infancy (SAVI) patients lead to excessive type I interferons and proinflammatory cytokines, which cause difficult-to-treat and sometimes fatal autoimmune disease. Here, in silico docking identified a potent STING antagonist SN-011 that binds with higher affinity to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP. SN-011 locks STING in an open inactive conformation, which inhibits interferon and inflammatory cytokine induction activated by 2'3'-cGAMP, herpes simplex virus type 1 infection, Trex1 deficiency, overexpression of cGAS-STING, or SAVI STING mutants. In Trex1-/- mice, SN-011 was well tolerated, strongly inhibited hallmarks of inflammation and autoimmunity disease, and prevented death. Thus, a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease.

RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.

The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) has emerged as a fundamental component fueling the anti-pathogen immunity. Because of its pivotal role in initiating innate immune response, the activity of cGAS must be tightly fine-tuned to maintain immune homeostasis in antiviral response. Here, we reported that neddylation modification was indispensable for appropriate cGAS-STING signaling activation. Blocking neddylation pathway using neddylation inhibitor MLN4924 substantially impaired the induction of type I interferon and proinflammatory cytokines, which was selectively dependent on Nedd8 E2 enzyme Ube2m. We further found that deficiency of the Nedd8 E3 ligase Rnf111 greatly attenuated DNA-triggered cGAS activation while not affecting cGAMP induced activation of STING, demonstrating that Rnf111 was the Nedd8 E3 ligase of cGAS. By performing mass spectrometry, we identified Lys231 and Lys421 as essential neddylation sites in human cGAS. Mechanistically, Rnf111 interacted with and polyneddylated cGAS, which in turn promoted its dimerization and enhanced the DNA-binding ability, leading to proper cGAS-STING pathway activation. In the same line, the Ube2m or Rnf111 deficiency mice exhibited severe defects in innate immune response and were susceptible to HSV-1 infection. Collectively, our study uncovered a vital role of the Ube2m-Rnf111 neddylation axis in promoting the activity of the cGAS-STING pathway and highlighted the importance of neddylation modification in antiviral defense.

Correction: RNF111-facilitated neddylation potentiates cGAS-mediated antiviral innate immune response.

[This corrects the article DOI: 10.1371/journal.ppat.1009401.].

Implantable metaverse with retinal prostheses and bionic vision processing.

We present an implantable metaverse featuring retinal prostheses in association with bionic vision processing. Unlike conventional retinal prostheses, whose electrodes are spaced equidistantly, our solution is to rearrange the electrodes to match the distribution of ganglion cells. To naturally imitate the human vision, a scheme of bionic vision processing is developed. On top of a three-dimensional eye model, our bionic vision processing is able to visualize the monocular image, binocular image fusion, and parallax-induced depth map.

Knockdown of LIMD2 inhibits the progression of ovarian carcinoma through ERK1/2 pathway.

BACKGROUND: The incidence rate of ovarian carcinoma (OC) is the third of the female reproductive system malignant tumors, while its mortality rate ranks first among causes of female reproductive system tumor related death in the world. METHODS: In the present research, we investigated the specific role of LIMD2 through LIMD2 knockdown in OC cells. RESULTS: The results of online analysis and expression detection proved that LIMD2 was up-regulated in human OC tissues and cells. Knockdown of LIMD2 inhibited the proliferation, migration and invasion in OC cells. LIMD2 knockdown promoted the apoptosis, as well as the expression of Cleaved-Caspase3 and Bax. Importantly, knockdown of LIMD2 promotes cell autophagy. LC3-II/I ratio and Beclin1 expression increased in LIMD2 knockdown cells, while P62 expression declined in LIMD2 knockdown cells. Additionally, the phosphorylation of ERK1/2 was inhibited by the knockdown of LIMD2 in SKOV3 and OVCAR3 cells. CONCLUSION: Knockdown of LIMD2 inhibits cell proliferation, migration, invasion and autophagy, and promotes the apoptosis through the ERK1/2 signaling pathway, suggesting that LIMD2-siRNA may be an effective molecule to prevent OC progression.

Anaerobic biodegradation of polycyclic aromatic hydrocarbons.

Although many anaerobic microorganisms that can degrade PAHs have been harnessed, there is still a large gap between laboratory achievements and practical applications. Here, we review the recent advances in the biodegradation of PAHs under anoxic conditions and highlight the mechanistic insights into the metabolic pathways and functional genes. Achievements of practical application and enhancing strategies of anaerobic PAHs bioremediation in soil were summarized. Based on the concerned issues during research, perspectives of further development were proposed including time-consuming enrichment, byproducts with unknown toxicity, and activity inhibition with low temperatures. In addition, meta-omics, synthetic biology and engineering microbiome of developing microbial inoculum for anaerobic bioremediation applications are discussed. We anticipate that integrating the theoretical research on PAHs anaerobic biodegradation and its successful application will advance the development of anaerobic bioremediation.

Lung Ultrasound in the Evaluation of Neonatal Respiratory Distress Syndrome.

OBJECTIVE: The purpose of this study is to examine the impact of bedside lung ultrasound (LUS) and LUS scores in the evaluating and grading of neonatal respiratory distress syndrome (NRDS). METHODS: We performed a prospective study on 80 children with suspected NRDS. Infants with a PaO2 -to-FiO2 ratio of <200, 200-300, and >300 mmHg were categorized as the "severe-NRDS group," "mild-NRDS group," and "non-NRDS group," respectively. Left and right lungs were divided into six areas, respectively. For each lung area, a 0- to 3-point score was given. RESULTS: The most common ultrasonic signs of NRDS include bilateral coalescent B-lines, thickened pleural line, and white lung without spared areas. Moreover, different LUS scores among non-NRDS, mild-NRDS, and severe-NRDS groups were identified (6.00 ± 4.033, 25.82 ± 3.778 and 27.90 ± 4.071, respectively; P < .05). When the cutoff value of LUS score was selected as 13 for the differentiation of non-NRDS from NRDS, the sensitivity and specificity were 96.9% and 93.3%, respectively, and the area under the curve (AUC) of receiver operating characteristics (ROC) was 0.938 (95% confidence interval [CI], 0.84-1.00). With a cutoff value of 26.5 for the differentiation between mild- and severe-ARDS, the AUC of ROC curve of the LUS score was 0.707 (95% CI, 0.58-0.83). Similar results were revealed as those with chest X-ray. CONCLUSION: This study showed that LUS and LUS scores complement each other, and are highly reliable and efficient in bedside radiological diagnostic investigations in newborns with NRDS.

WD-YOLO: A More Accurate YOLO for Defect Detection in Weld X-ray Images.

X-ray images are an important industrial non-destructive testing method. However, the contrast of some weld seam images is low, and the shapes and sizes of defects vary greatly, which makes it very difficult to detect defects in weld seams. In this paper, we propose a gray value curve enhancement (GCE) module and a model specifically designed for weld defect detection, namely WD-YOLO. The GCE module can improve image contrast to make detection easier. WD-YOLO adopts feature pyramid and path aggregation designs. In particular, we propose the NeXt backbone for extraction and fusion of image features. In the YOLO head, we added a dual attention mechanism to enable the model to better distinguish between foreground and background areas. Experimental results show that our model achieves a satisfactory balance between performance and accuracy. Our model achieved 92.6% mAP@0.5 with 98 frames per second.

Unique regulator SrpR mediates crosstalk between efflux pumps TtgABC and SrpABC in Pseudomonas putida B6-2 (DSM 28064).

The coexistence of multiple homologous resistance-nodulation-division (RND) efflux pumps in bacteria is frequently described with overlapping substrate profiles. However, it is unclear how bacteria balance their transcription in response to the changing environment. Here, we characterized a repressor, SrpR, in Pseudomonas putida B6-2 (DSM 28064), whose coding gene is adjacent to srpS that encodes the local repressor of the RND-type efflux pump SrpABC gene cluster. SrpR was demonstrated as a specific repressor of another RND efflux pump gene cluster ttgABC that is locally repressed by TtgR. SrpR was found to be capable of binding to the ttgABC operator with a higher affinity (KD , 138.0 nM) compared to TtgR (KD , 15.4 µM). EMSA and ß-galactosidase assays were performed to survey possible effectors of SrpR with 35 available chemicals being tested. Only 2,3,4-trichlorophenol was identified as an effector of SrpR. A regulation model was then proposed, representing a novel strategy for balancing the efflux systems with partially overlapping substrate profiles. This study highlights sophisticated interactions among the RND efflux pumps in a Pseudomonas strain, which may endow bacteria with certain advantages in a fluctuant environment.

Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis. TRIAL REGISTRATION:  This study is registered with ClinicalTrials.gov, number NCT04490447.

Transjugular Intrahepatic Portosystemic Shunt for Portal Vein Cavernous Transformation: A Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is technically challenging in the treatment of portal vein cavernous transformation (PVCT), and there is no high-quality evidence regarding whether it is an option for patients with PVCT. We carried out a systematic review and meta-analysis to assess the feasibility and safety of TIPS for PVCT. METHODS: Systematic search of PubMed, Chinese National Knowledge Infrastructure (CNKI) database, Cochrane Library, Embase, and Wanfang database through December 2021 for appropriate studies reporting efficacy and safety in patients with PVCT undergoing TIPS. The main outcome included the technical success rate, postoperative rebleeding rate, postoperative hepatic encephalopathy rate, stent patency rate, preoperative, and postoperative portal pressure. RESULTS: Ten studies, including 292 patients were included. Our results showed that TIPS was technically successful in 82.97% (95% confidence interval [CI]: 77.14%-88.41%, p = 0.297) with low heterogeneity (I2 = 18.39%, p = 0.279). Postoperative rebleeding occurred in 9.56% (95% CI: 4.55%-16.77%, p = 0.073) with moderate heterogeneity (I2 = 46.45%, p = 0.06). Postoperative hepatic encephalopathy occurred in 18.55% (95% CI: 9.23%-27.05%, p = 0.343) with moderate heterogeneity (I2 = 48.62%, p = 0.049). Stent patency during follow-up was in 78.43% (95% CI: 70.74%-85.20%, p = 0.805) with low heterogeneity (I2 = 0%, p = 0.654). Postoperative portal pressure significantly reduced (WMD = 12.79 mm Hg, 95% CI: 12.09-13.48 mm Hg, p < 0.00001) with high heterogeneity (I2 = 61.4%, p = 0.02). Both Begg test and funnel plot showed that there was no significant publication bias. CONCLUSIONS: TIPS is feasible and safe in patients with PVCT and PVCT should not be considered an absolute contraindication to TIPS.

NSUN5 Facilitates Viral RNA Recognition by RIG-I Receptor.

The RIG-I receptor induces the innate antiviral responses upon sensing RNA viruses. The mechanisms through which RIG-I optimizes the strength of the downstream signaling remain incompletely understood. In this study, we identified that NSUN5 could potentiate the RIG-I innate signaling pathway. Deficiency of NSUN5 enhanced RNA virus proliferation and inhibited the induction of the downstream antiviral genes. Consistently, NSUN5-deficient mice were more susceptible to RNA virus infection than their wild-type littermates. Mechanistically, NSUN5 bound directly to both viral RNA and RIG-I, synergizing the recognition of dsRNA by RIG-I. Collectively, to our knowledge, this study characterized NSUN5 as a novel RIG-I coreceptor, playing a vital role in restricting RNA virus infection.

Revealing the role of interfacial heterogeneous nucleation in the metastable thin film growth of rare-earth nickelate electronic transition materials.

Although rare-earth nickelates (ReNiO3, Re ≠ La) exhibit abundant electronic phases and widely adjustable metal to insulator electronic transition properties, their practical electronic applications are largely impeded by their intrinsic meta-stability. Apart from elevating the oxygen reaction pressure, heterogeneous nucleation is expected to be an alternative strategy that enables the crystallization of ReNiO3 at low meta-stability. In this work, the respective roles of high oxygen pressure and heterogeneous interface in triggering ReNiO3 thin film growth in the metastable state are revealed. ReNiO3 (Re = Nd, Sm, Eu, Gd and Dy) thin films grown on a LaAlO3 single crystal substrate show effective crystallization at atmospheric pressure without the necessity to apply high oxygen pressure, suggesting that the interfacial bonding between the ReNiO3 and substrates can sufficiently reduce the positive Gibbs formation energy of ReNiO3, which is further verified by the first-principles calculations. Nevertheless, the abrupt electronic transitions only appear in ReNiO3 thin films grown at high oxygen pressure, in which case the oxygen vacancies are effectively eliminated via high oxygen pressure reactions as indicated by near-edge X-ray absorption fine structure (NEXAFS) analysis. This work unveils the synergistic effects of heterogeneous nucleation and high oxygen pressure on the growth of high quality ReNiO3 thin films.

Macrophage cell membrane-based nanoparticles: a new promising biomimetic platform for targeted delivery and treatment.

Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic.

Variation of microRNA expression in the human placenta driven by population identity and sex of the newborn.

BACKGROUND: Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts. Here, we analyzed microRNA (miRNA) expression in human placental samples derived from 36 individuals representing four genetically distinct human populations: African Americans, European Americans, South Asians, and East Asians. All samples were collected at the same hospital following a unified protocol, thus minimizing potential biases that might influence the results. RESULTS: Sequence analysis of the miRNA fraction yielded 938 annotated and 70 novel miRNA transcripts expressed in the placenta. Of them, 82 (9%) of annotated and 11 (16%) of novel miRNAs displayed quantitative expression differences among populations, generally reflecting reported genetic and mRNA-expression-based distances. Several co-expressed miRNA clusters stood out from the rest of the population-associated differences in terms of miRNA evolutionary age, tissue-specificity, and disease-association characteristics. Among three non-environmental influenced demographic parameters, the second largest contributor to miRNA expression variation after population was the sex of the newborn, with 32 miRNAs (3% of detected) exhibiting significant expression differences depending on whether the newborn was male or female. Male-associated miRNAs were evolutionarily younger and correlated inversely with the expression of target mRNA involved in neuron-related functions. In contrast, both male and female-associated miRNAs appeared to mediate different types of hormonal responses. Demographic factors further affected reported imprinted expression of 66 placental miRNAs: the imprinting strength correlated with the mother's weight, but not height. CONCLUSIONS: Our results showed that among 12 assessed demographic variables, population affiliation and fetal sex had a substantial influence on miRNA expression variation among human placental samples. The effect of newborn-sex-associated miRNA differences further led to expression inhibition of the target genes clustering in specific functional pathways. By contrast, population-driven miRNA differences might mainly represent neutral changes with minimal functional impacts.

First Detection of a Cluster Novel HIV-1 Second-Generation Recombinant (CRF01_AE/CRF07_BC) among Men Who Have Sex with Men in Nanjing, Eastern China.

INTRODUCTION: A large number of unique recombinant forms have been found in China in recent years. This study aimed to report on a cluster of novel HIV-1 recombinants. METHODS: We constructed phylogenetic trees using the maximum likelihood (ML) method with 1,000 bootstrap replicates in IQ-TREE 1.6.8 software and determined recombination break points using SimPlot 3.5.1. RESULTS: Overall, 9 near-full-length genome (NFLG) sequences were reported in this study, including 1 circulation recombinant form (CRF)01_AE NFLG sequence and 8 highly similar novel HIV-1 second-generation recombinants composed of CRF01_AE and CRF07_BC (CRF105_0107) isolated from a cluster HIV-positive male subjects infected among men who have sex with men (MSM) in Nanjing, eastern China. The phylogenetic analysis of NFLG showed 1 sequence named "nj16" to have at least 11 breakpoints inner virus and 7 other sequences to have at least 10 breakpoints inner virus. Our findings further showed as follows: first, this is the first time that a cluster of novel CRF105_0107 HIV-1 strains were identified among MSM in Nanjing, Jiangsu. Second, the Chinese "4a" cluster of CRF01_AE which mainly circulating in northern China has spread in Jiangsu for more than 15 years. Third, HIV-1 recombination events were active in Nanjing city, and novel recombinants could spread rapidly through some small-scale transmission networks. CONCLUSION: The continued emergence of novel recombinant HIV-1 strains in Nanjing suggests dynamics and complexity in the HIV epidemic among MSM in Jiangsu province. Further investigations and molecular epidemiological research should be taken to monitor and understand transmission networks among MSM.

Selective Extraction and Complexation Studies for Thorium(IV) with Bis-triamide Extractants: Synthesis, Solvent Extraction, EXAFS, and DFT.

Three octyl-extended bis-triamide extractants (L1-L3) were designed and synthesized for the selective solvent extraction of Th(IV) over U(VI) in a kerosene-HNO3 system. L1 and L2 exhibited good extraction property and selectivity toward Th(IV) over U(VI) and reached extraction equilibrium within 10 min. In a wide range of a HNO3 concentration from 0.1 to 3.0 M, the separation factor of Th(IV) over U(VI) (SFTh/U) of L1 and L2 ranged from 12.1 ± 1.6 to 123.0 ± 20.2 and 15.2 ± 2.4 to 88.1 ± 14.9, respectively. Slope analysis indicated that Th(IV) was extracted as different species under different HNO3 concentrations, in which the slopes were 2.08 ± 0.20, 1.61 ± 0.03, and 1.54 ± 0.03 for L1 and 2.37 ± 0.22, 2.07 ± 0.17, and 1.76 ± 0.18 for L2 under 0.1, 1.0, and 3.0 M HNO3, respectively. A continuous variation method (Job plot) illustrated a 1.5:1 ligand/thorium (L/Th) ratio in a methanol phase, indicating that L1/L2 and Th(IV) could form mixed 1:1 and 2:1 L/Th extracted complexes. Extended X-ray absorption fine structure (EXAFS) and density functional theory (DFT) calculations revealed that the extracted complexes of L1 and L2 with Th during the extraction process at 0.1 M HNO3 were [2L1·Th·3(NO3)]+ and [2L2·Th·3(NO3)]+.

The impact of COVID-19 pandemic on HIV care continuum in Jiangsu, China.

BACKGROUND: The COVID-19 pandemic seriously threatens general public health services globally. This study aimed to evaluate the impact of the COVID-19 pandemic on the HIV care continuum in Jiangsu province, China. METHODS: Data on newly diagnosed HIV persons for analysis were retrieved from Chinas' web-based Comprehensive Response Information Management System (CRIMS) for HIV/AIDS from 2016 to 2020. We recorded data for the first 3 months (January to March, 2020) of strictly implementing COVID-19 measures from publicly available disease databases of the Jiangsu provincial Health Committee. We used seasonal autoregressive integrated moving average (SARIMA) and exponential smoothing in forecasting the parameters. Subgroup differences were accessed using Chi-square tests. RESULTS: Compared to the estimated proportions, the HIV testing rates decreased by 49.0% (919,938) in the first three months of implementing COVID-19 measures. Of an estimated 1555 new HIV diagnosis expected in the same period, only 63.0% (980) new diagnoses were recorded. According to actual data recorded during the said period, 980 positively tested persons received confirmatory tests, of which 71.4% (700) were reportedly linked to care. And only 49.5% (235) out of the expected 475 newly diagnosed HIV persons received CD4 cell count testing. Meanwhile 91.6% (208) of newly diagnosed HIV persons who received CD4 count tests reportedly initiated antiretroviral therapy (ART) compared to the 227 expected. Compared to the same period from 2016 to 2019, PLWH less than 30 years old and migrants were more likely to be affected by the COVID-19 policies. CONCLUSIONS: The COVID-19 pandemic negatively impacted HIV healthcare systems in Jiangsu, China. Further measures that can counter the impact of the pandemic are needed to maintain the HIV care continuum.