Human lens epithelial-secreted exosomes attenuate ocular angiogenesis via inhibiting microglial activation.

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2'-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation.

M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy.

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

Quantitative real-time phase microscopy for extended depth-of-field imaging based on the 3D single-shot differential phase contrast (ssDPC) imaging method.

Optical diffraction tomography (ODT) is a promising label-free imaging method capable of quantitatively measuring the three-dimensional (3D) refractive index distribution of transparent samples. In recent years, partially coherent ODT (PC-ODT) has attracted increasing attention due to its system simplicity and absence of laser speckle noise. Quantitative phase imaging (QPI) technologies represented by Fourier ptychographic microscopy (FPM), differential phase contrast (DPC) imaging and intensity diffraction tomography (IDT) need to collect several or hundreds of intensity images, which usually introduce motion artifacts when shooting fast-moving targets, leading to a decrease in image quality. Hence, a quantitative real-time phase microscopy (qRPM) for extended depth of field (DOF) imaging based on 3D single-shot differential phase contrast (ssDPC) imaging method is proposed in this research study. qRPM incorporates a microlens array (MLA) to simultaneously collect spatial information and angular information. In subsequent optical information processing, a deconvolution method is used to obtain intensity stacks under different illumination angles in a raw light field image. Importing the obtained intensity stack into the 3D DPC imaging model is able to finally obtain the 3D refractive index distribution. The captured four-dimensional light field information enables the reconstruction of 3D information in a single snapshot and extending the DOF of qRPM. The imaging capability of the proposed qRPM system is experimental verified on different samples, achieve single-exposure 3D label-free imaging with an extended DOF for 160 µm which is nearly 30 times higher than the traditional microscope system.

Dynamic Virtual Fixture Generation Based on Intra-Operative 3D Image Feedback in Robot-Assisted Minimally Invasive Thoracic Surgery.

This paper proposes a method for generating dynamic virtual fixtures with real-time 3D image feedback to facilitate human-robot collaboration in medical robotics. Seamless shared control in a dynamic environment, like that of a surgical field, remains challenging despite extensive research on collaborative control and planning. To address this problem, our method dynamically creates virtual fixtures to guide the manipulation of a trocar-placing robot arm using the force field generated by point cloud data from an RGB-D camera. Additionally, the "view scope" concept selectively determines the region for computational points, thereby reducing computational load. In a phantom experiment for robot-assisted port incision in minimally invasive thoracic surgery, our method demonstrates substantially improved accuracy for port placement, reducing error and completion time by 50% (p=1.06×10-2) and 35% (p=3.23×10-2), respectively. These results suggest that our proposed approach is promising in improving surgical human-robot collaboration.

Lens epithelial cell-derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR-146a-5p.

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)-derived exosomes (Lec-exo) is largely unknown. Thus, we aimed to investigate whether Lec-exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen-induced retinopathy and laser-induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec-exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high-throughput miRNAs sequencing analysis detected that miR-146a-5p was enriched in Lec-exo. Mechanistically, exosomal miR-146a-5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec-exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.

The Exosome-Transmitted lncRNA LOC100132249 Induces Endothelial Dysfunction in Diabetic Retinopathy.

Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative DR (PDR-exo) promote proliferation, migration, and tube formation of human retinal vascular endothelial cells (HRVECs). We identified long noncoding RNA (lncRNA) LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of miRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition promoter SNAI1 via activation of the Wnt/ß-catenin pathway and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis and may shed light on new therapeutic strategies for future treatment of DR. ARTICLE HIGHLIGHTS: This study provides the first evidence that exosomes derived from vitreous humor from patients with proliferative diabetic retinopathy participate in angiogenesis. The findings demonstrate an unreported long noncoding RNA (lncRNA), LOC100132249, by exosomal sequencing of vitreous humor. The newly found lncRNA LOC100132249, mainly derived from endothelial cells, promotes angiogenesis via an miRNA-199a-5p/SNAI1/Wnt/ß-catenin axis in a pro-endothelial-mesenchymal transition manner.

Thermal batteries based on inverse barocaloric effects.

To harvest and reuse low-temperature waste heat, we propose and realize an emergent concept-barocaloric thermal batteries based on the large inverse barocaloric effect of ammonium thiocyanate (NH4SCN). Thermal charging is initialized upon pressurization through an order-to-disorder phase transition, and the discharging of 43 J g-1 takes place at depressurization, which is 11 times more than the input mechanical energy. The thermodynamic equilibrium nature of the pressure-restrained heat-carrying phase guarantees stable long-duration storage. The barocaloric thermal batteries reinforced by their solid microscopic mechanism are expected to substantially advance the ability to take advantage of waste heat.

Role of Intramuscular Connective Tissue in Water Holding Capacity of Porcine Muscles.

BACKGROUND: This study evaluated the influence of intramuscular connective tissue (IMCT) on structural shrinkage and water loss during cooking. Longissimus thoracis (LT), semimembranosus (SM) and semitendinosus (ST) muscles were cut and boiled for 30 min in boiling water, followed by detection of water holding capacity (WHC), tenderness, fiber volume shrinkage and protein denaturation. RESULTS: Compared with LT and SM, ST had the best WHC and lowest WBSF and area shrinkage ratio. The mobility of immobilized water (T22) was key to holding the water of meat. ST contained the highest content of total and heat-soluble collagen. On the contrary, ST showed the lowest content of cross-links and decorin, which indicate the IMCT strength of ST is weaker than the other two. The heat-soluble collagen is positively correlated to T22. CONCLUSIONS: The shrinkage of heat-insoluble IMCT on WHC and WBSF may partly depend on the structural strength changes of IMCT components rather than solely caused by quantitative changes of IMCT.

Impact Velocity Measurement Method Based on Trajectory and Impact Position.

The impact velocity of falling weight is an instantaneous quantity. Currently, measurement of impact velocity relies on high-speed sensors to capture the moment of impact. The trajectory-position measurement method (TPMM) is proposed in this study. The main steps are: (1) The impact position is used to capture the impact time. It can be measured when the falling weight is stationary. (2) The discrete falling trajectory is measured and a new empirical regression algorithm is proposed to fit the expression of falling trajectory. (3) The impact velocity is obtained by taking the impact time into the first derivative of the trajectory expression. For 1-5 m falling height, the simulation shows that the relative maximum error and relative expanded uncertainty of the proposed method are less than 0.481% and 0.442%, respectively. Then, the actual experiment is carried out to verify the simulation. The proposed method has high accuracy and low uncertainty. The reasons are: (1) Only a low-speed displacement sensor is need for impact velocity measurement. It is easier to improve accuracy and stability of a low-speed sensor. (2) The empirical regression algorithm can improve the stability of falling trajectory fitting.

lncRNA ZFAS1 Positively Facilitates Endothelial Ferroptosis via miR-7-5p/ACSL4 Axis in Diabetic Retinopathy.

Accumulating evidence has suggested the significant role of long noncoding RNAs (lncRNA) in regulating ferroptosis, while its regulatory mechanism in diabetic retinopathy (DR) remains unelucidated. In this work, we first demonstrated that lncRNA zinc finger antisense 1 (ZFAS1) is upregulated in high glucose-cultured human retinal endothelial cells (hRECs) and ZFAS1 inhibition attenuated high glucose- (HG-) induced ferroptosis, which was evidenced by cell viability, total iron and ferrous iron levels, reactive oxygen species (ROS) level, and Glutathione Peroxidase 4 (GPX4) expression detection. Mechanistically, we validated that ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in DR.

Exploring the multi-level regulation of lignocellulases in the filamentous fungus Trichoderma guizhouense NJAU4742 from an omics perspective.

BACKGROUND: Filamentous fungi are highly efficient at deconstructing plant biomass by secreting a variety of enzymes, but the complex enzymatic regulation underlying this process is not conserved and remains unclear. RESULTS: In this study, cellulases and xylanases could specifically respond to Avicel- and xylan-induction, respectively, in lignocellulose-degrading strain Trichoderma guizhouense NJAU4742, however, the differentially regulated cellulases and xylanases were both under the absolute control of the same TgXyr1-mediated pathway. Further analysis showed that Avicel could specifically induce cellulase expression, which supported the existence of an unknown specific regulator of cellulases in strain NJAU4742. The xylanase secretion is very complex, GH10 endoxylanases could only be induced by Avicel, while, other major xylanases were significantly induced by both Avicel and xylan. For GH10 xylanases, an unknown specific regulator was also deduced to exist. Meanwhile, the post-transcriptional inhibition was subsequently suggested to stop the Avicel-induced xylanases secretion, which explained the specifically high xylanase activities when induced by xylan in strain NJAU4742. Additionally, an economical strategy used by strain NJAU4742 was proposed to sense the environmental lignocellulose under the carbon starvation condition, that only slightly activating 4 lignocellulose-degrading genes before largely secreting all 33 TgXyr1-controlled lignocellulases if confirming the existence of lignocellulose components. CONCLUSIONS: This study, aiming to explore the unknown mechanisms of plant biomass-degrading enzymes regulation through the combined omics analysis, will open directions for in-depth understanding the complex carbon utilization in filamentous fungi.

Highly Stable, Graphene-Wrapped, Petal-like, Gap-Enhanced Raman Tags.

Gap-enhanced Raman tags (GERTs) were widely used in cell or biological tissue imaging due to their narrow spectral linewidth, weak photobleaching effect, and low biological matrix interference. Here, we reported a new kind of graphene-wrapped, petal-like, gap-enhanced Raman tags (GP-GERTs). The 4-Nitrobenzenethiol (4-NBT) Raman reporters were embedded in the petal-like nanogap, and graphene was wrapped on the surface of the petal-like, gap-enhanced Raman tags. Finite-difference time-domain (FDTD) simulations and Raman experimental studies jointly reveal the Raman enhancement mechanism of graphene. The SERS enhancement of GP-GERTs is jointly determined by the petal-like "interstitial hotspots" and electron transfer between graphene and 4-NBT molecules, and the total Raman enhancement factor (EF) can reach 1010. Mesoporous silica was grown on the surface of GP-GERTs by tetraethyl orthosilicate hydrolysis to obtain Raman tags of MS-GP-GERTs. Raman tag stability experiments showed that: MS-GP-GERTs not only can maintain the signal stability in aqueous solutions of different pH values (from 3 to 12) and simulated the physiological environment (up to 72 h), but it can also stably enhance the signal of different Raman molecules. These highly stable, high-signal-intensity nanotags show great potential for SERS-based bioimaging and multicolor imaging.

Vitrectomy with Inverted Fovea-Sparing Internal Limiting Membrane for Myopic Foveoschisis.

PURPOSE: To evaluate the efficacy and safety of vitrectomy with inverted fovea-sparing internal limiting membrane, as a modified surgical technique in the treatment of the eyes with myopic foveoschisis. METHODS: This study was based on a consecutive, interventional case series. A standard 25-gauge (25-G), 3-port pars plana vitrectomy combined with inverted fovea-sparing internal limiting membrane was performed on 13 eyes. Preoperative and postoperative best-corrected visual acuity, optical coherence tomography image, and central foveal thickness were analyzed. Patients were followed up for at least 6 months. RESULTS: All 13 eyes showed dramatical resolution of myopic foveoschisis during the follow-up. The mean logarithm of minimum angle of resolution best-corrected visual acuity showed remarkable improvement from 1.06 ± 0.42 to 0.45 ± 0.25 (p < 0.0001; paired t-test). The mean central foveal thickness significantly decreased from 479.62 ± 113.16 µm to 372.38 ± 88.12 µm, 316.18 ± 73.97 µm, and 272.40 ± 61.32 µm postoperatively at 1 month, 3 months, and 6 months, respectively (p < 0.0001; paired t-test; preoperation vs. latest follow-up). CONCLUSIONS: Vitrectomy with inverted fovea-sparing internal limiting membrane can resolve myopic foveoschisis with high efficacy and safety.

Müller glia-derived exosomal miR-9-3p promotes angiogenesis by restricting sphingosine-1-phosphate receptor S1P1 in diabetic retinopathy.

Diabetic retinopathy is a heterogeneous retinal degenerative disease with the microvascular dysfunction being recognized as a hallmark of the advanced stage. In this study, we demonstrated that exosomes collected from the vitreous humor of proliferative diabetic retinopathy patients promoted proliferation, migration and tube formation ability of primary human retinal endothelial cells via its elevated miR-9-3p expression level. Müller glia cells were further recognized as the sole source of the aberrantly expressed miR-9-3p, and both in vitro and in vivo experiments validated that Müller glia-derived exosomes aggravate vascular dysfunction under high glucose. Mechanistically, exosomal miRNA-9-3p was transferred to retinal endothelial cells and bound to the sphingosine-1-phosphate receptor S1P1 coding sequence, which subsequently activated VEGFR2 phosphorylation and internalization in the presence or absence of exogenous VEGF-A. We successfully orchestrated the dynamic crosstalk between retinal Müller glia cells and endothelial cells in pathological condition, which may provide a novel biomarker or promising therapeutic agents for the treatment of diabetic retinopathy.

Serum Exosomal Circular RNA Expression Profile and Regulative Role in Proliferative Diabetic Retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR), as one of the main microvascular complications of diabetes mellitus, seriously threatens the visual function of the working-age population; yet, the underlying pathogenesis is still poorly understood. This study aimed to identify the distinct exosomal circular RNA (circRNA) expression in PDR serum and preliminarily explore the potential pro-angiogenic mechanism of specific exosomal circRNAs. METHODS: We collected serum samples from 10 patients with PDR and 10 patients with age-matched senile cataract to detect the exosomal differentially expressed genes (DEGs) of circRNAs via high-throughput sequencing, followed by validation with quantitative real-time PCR (qRT-PCR). Next, bioinformatics analyses including competitive endogenous RNA (ceRNA) network, protein-protein interaction network (PPI), and functional enrichment analyses were performed. In addition, the potential function of circFndc3b (hsa_circ_0006156) derived from high-glucose-induced endothelial cells was analyzed in human retinal vascular endothelial cells (HRVECs). RESULTS: In total, 26 circRNAs, 106 microRNAs (miRNAs), and 2,264 messenger RNAs (mRNAs) were identified as differentially expressed in PDR serum exosomes compared with cataract serum exosomes (fold change > 1, P < 0.05). A circRNA-miRNA-mRNA ceRNA network was established. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the mRNAs were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, Wnt signaling pathway, and VEGF signaling pathway. The PPI network and module analysis identified 10 hub genes, including RhoA, Cdc42, and RASA1. Finally, circFndc3b and exosomes derived from high-glucose-induced endothelial cells were identified with the capability to facilitate angiogenesis in vitro. CONCLUSION: Aberrant profiling of exosomal circRNAs in PDR serum was identified. CircFndc3b derived from high-glucose-induced endothelial cells may play an important role in the angiogenesis of PDR.

Pembrolizumab for choroidal metastases from non-small cell lung cancer: a case report and literature review.

We described a 65-year-old male with choroidal metastases (CM) from non-small cell lung cancer (NSCLC). Pembrolizumab (Keytruda) combined with pemetrexed and capecitabine achieved excellent outcomes. After two cycles of pembrolizumab and chemotherapy, blurred vision and left eye pain were significantly relieved. Imaging and ophthalmologic examinations demonstrated complete resolution of the CM, as well as reduction of pulmonary shadow. CM from NSCLC shows complete and durable response to pembrolizumab and chemotherapy. We suggesting that immunotherapy combined with chemotherapy is a promising treatment for CM from NSCLC.

PERFLUOROCARBON LIQUID-ASSISTED INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS INTERNAL LIMITING MEMBRANE PEELING FOR HIGHLY MYOPIC MACULAR HOLE RETINAL DETACHMENT.

PURPOSE: To compare the efficacy of a modified perfluorocarbon liquid-assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes. METHODS: This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid-assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery. RESULTS: Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044). CONCLUSION: The perfluorocarbon liquid-assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.

Rosemary and Tea Tree Essential Oils Exert Antibiofilm Activities In Vitro against Staphylococcus aureus and Escherichia coli.

ABSTRACT: The purpose of the present study was to determine the bioactive compounds in rosemary essential oil (REO) and tea tree essential oil (TEO) and to investigate their antibacterial and antibiofilm activities against Staphylococcus aureus and Escherichia coli in vitro. The MIC and MBC assays were performed to assess the antibacterial activity of these two EOs against S. aureus and E. coli with the broth microdilution method. A crystal violet assay was used to ascertain the effects of EOs on the biofilm formation of the test strains, and a tetrazolium bromide (MTT) assay was used to measure the level of inactivation of mature biofilms by EOs. Gas chromatography-mass spectrometry revealed 15 compounds in REO and 27 compounds in TEO, representing 97.78 and 98.13% of the total EO, respectively. Eucalyptol and α-pinene were found in high concentrations in REO, and the two major compounds in TEO were 4-terpineol and terpinolene. The MICs of REO for the two S. aureus and E. coli test strains were both 0.5 mg/mL, and the MICs of TEO for the two strains were both 0.25 mg/mL. Therefore, these EOs can significantly inhibit the formation of biofilms and induced morphological biofilm changes, as verified by scanning electron microscopy. Both EOs had destructive effects on the mature biofilm of the two test strains. TEO was more inhibitory than REO for biofilm formation by the two test strains.

Competing Dissolution Pathways and Ligand Passivation-Enhanced Interfacial Stability of Hybrid Perovskites with Liquid Water.

Material instability issues, especially moisture degradation in ambient operating environments, limit the practical application of hybrid perovskite in photovoltaic and light-emitting devices. Very recent experiments demonstrate that ligand passivation can effectively improve the surface moisture tolerance of hybrid perovskites. In this work, the interfacial stability of as-synthesized pristine and alkylammonium-passivated methylammonium lead iodide (MAPbI3) with liquid water is systematically investigated using molecular dynamics simulations and reaction kinetics models. Interestingly, the more hydrophilic [PbI2]0 surface is more stable than the less hydrophilic [MAI]0 surface because of the higher polarity of the former surface. Linear alkylammoniums significantly stabilize the [MAI]0 surface with highly reduced (by 1-2 orders of magnitude) dissociation rates of both MA+ and ligands themselves, while branched ligands, surprisingly, lead to higher dissociation rates as the surface coverage increases. Such anomalous behavior is attributed to the aggregation-assisted dissolution of surfactant-like ligands as micelles during the degradation process. Short-chain linear alkylammonium at the full surface coverage is found to be the optimal ligand to stabilize the [MAI]0 surface. This work not only provides fundamental insights into the ionic dissolution pathways and mechanisms of hybrid perovskites in water but also inspires the design of highly stable hybrid perovskites with ligand passivation layers. The computational framework developed here is also transferrable to the investigation of surface passivation chemistry for weak ionic materials in general.

Colossal barocaloric effects in plastic crystals.

Refrigeration is of vital importance for modern society-for example, for food storage and air conditioning-and 25 to 30 per cent of the world's electricity is consumed for refrigeration1. Current refrigeration technology mostly involves the conventional vapour compression cycle, but the materials used in this technology are of growing environmental concern because of their large global warming potential2. As a promising alternative, refrigeration technologies based on solid-state caloric effects have been attracting attention in recent decades3-5. However, their application is restricted by the limited performance of current caloric materials, owing to small isothermal entropy changes and large driving magnetic fields. Here we report colossal barocaloric effects (CBCEs) (barocaloric effects are cooling effects of pressure-induced phase transitions) in a class of disordered solids called plastic crystals. The obtained entropy changes in a representative plastic crystal, neopentylglycol, are about 389 joules per kilogram per kelvin near room temperature. Pressure-dependent neutron scattering measurements reveal that CBCEs in plastic crystals can be attributed to the combination of extensive molecular orientational disorder, giant compressibility and highly anharmonic lattice dynamics of these materials. Our study establishes the microscopic mechanism of CBCEs in plastic crystals and paves the way to next-generation solid-state refrigeration technologies.