The Importance of Exosomal PD-L1 in Cancer Progression and Its Potential as a Therapeutic Target.

Binding of programmed cell death ligand 1 (PD-L1) to its receptor programmed cell death protein 1 (PD-1) can lead to the inactivation of cytotoxic T lymphocytes, which is one of the mechanisms for immune escape of tumors. Immunotherapy based on this mechanism has been applied in clinic with some remaining issues such as drug resistance. Exosomal PD-L1 derived from tumor cells is considered to play a key role in mediating drug resistance. Here, the effects of various tumor-derived exosomes and tumor-derived exosomal PD-L1 on tumor progression are summarized and discussed. Researchers have found that high expression of exosomal PD-L1 can inhibit T cell activation in in vitro experiments, but the function of exosomal PD-L1 in vivo remains controversial. In addition, the circulating exosomal PD-L1 has high potential to act as an indicator to evaluate the clinical effect. Moreover, therapeutic strategy targeting exosomal PD-L1 is discussed, such as inhibiting the biogenesis or secretion of exosomes. Besides, some specific methods based on the strategy of inhibiting exosomes are concluded. Further study of exosomal PD-L1 may provide an effective and safe approach for tumor treatment, and targeting exosomal PD-L1 by inhibiting exosomes may be a potential method for tumor treatment.

Fan-Shaped Thin Fat Pedicles for Tear Trough Correction Through a Layer-Level Fixation: A Modified Transconjunctival Blepharoplasty.

ABSTRACT: Fat repositioning is an effective way to treat tear trough deformity (TTD) in Asians. Recent techniques mainly focused on the fixation technique, whereas how to precisely shape and individually quantify the fat pedicle has been ignored. This article introduced an individualized, targeted, and tension-free technique to fabricate a fan-shaped thin septum fat pedicle for repositioning. Furthermore, a layer-level fixation method was advocated to provide sufficient, continuous, uninterrupted filling of the TTD. From January 1, 2009, to December 31, 2018, 492 patients underwent this procedure. Through a transconjunctival incision, a continuous fan-shaped, tension-free, customized septum fat pedicle was precisely designed to match the TTD anatomy. The pedicle could either be elongated, or thickened, or debulked, or translocated, to meet the patients' individual needs. At the same time, a layer-level fat pedicle fixation technique was applied to fully interrupt the TTD. The mean operation time was 60 ±â€Š9.3 minutes. All patients demonstrated a significant improvement with elimination of both eye bags and TTD. High satisfaction was noted among the patients. No obvious resorption of the fat pedicles was observed, and the lower lid contour improvements were durable. One infection occurred after 3 days of surgery, and was resolved by removal of the suture followed by topical application of iodine and oral antibiotics for 3 to 5 days. No other complications were observed. Precisely repositioning transconjunctival fat using a layer-level fixation technique with a fan-shaped thin fat pedicle under a subperiosteal plane is an effective, lasting, and safe approach for individually treating TTD.

Enophthalmos: Exploration of Quantitative Treatment With Retro-Orbital Fat Globules Injection.

Craniomaxillofacial and plastic surgeons are often confronted with patients who present with enophthalmos caused mainly by trauma. In many patients, one-stage reconstruction repairs only the bony orbit, leaving intact the disfiguring enophthalmos. Thus, some filler is needed to restore the normal volume of the orbit. The authors describe a technique to correct such deformation safely and effectively. Data were collected from 30 enophthalmic patients (average age 36.67 ±â€Š11.66 years) who underwent retro-ocular injections of fat globules between August 2014 and July 2018. CT helped identify a safe injection site, and specific CT measurements quantified the volume of fat globules required. There was a significant difference between the preoperative and postoperative values for lateral orbital protrusion (P < .01), superior orbital protrusion (P < .01), and orbital volume (P < .01). Most patients were satisfied with the outcome. There were no significant complications. Injecting fat globules into the retro-orbital area is an effective technique for correcting enophthalmos deformity.

Survey of In Situ Splitting Rib Harvesting Surgery for Orbital Deformity: Follow-Up.

BACKGROUND: Our previous study indicated that in situ splitting rib harvesting surgery clinically reduced in related complications compared with the traditional surgical approach in the early stage, but there are few studies pay close attention to long-term recovery of donor area after rib harvesting. In this study, the authors conducted a follow-up study on recovery condition of donor and graft site of patients after in situ rib splitting grafting or simple whole rib grafting surgery. METHODS: Between 2013 and 2016, 8 Chinese patients with orbital deformity were corrected using autogenous rib, of which 3 patients received conventional rib harvesting surgery, 3 patients received in situ splitting harvesting surgery, and 2 patients underwent both. In all patients, 3-dimensional computed tomography study of donor site and graft site were performed before and after operation. The ribs of donor site and graft site volume measurement were assessed using computed tomography 7 days and 12 months postoperation. RESULTS: After 12 months operation, the integrity of rib arch recovered 94.1 ±â€Š2.2% after in situ splitting rib harvesting, compared with 41.4 ±â€Š5.0% after whole rib harvesting. The volume of grafted rib in situ splitting rib harvesting group reduced 69.8 ±â€Š10.0% after 12 months operation compared with the volume after 1 week operation, and the reduced volume of ribs in whole rib harvesting group was 73.62 ±â€Š9.5%. CONCLUSION: Rib regeneration occurred more quickly by in situ rib splitting harvesting approach compared with the traditional surgical approach.

MPK3/MPK6 are involved in iron deficiency-induced ethylene production in Arabidopsis.

Iron (Fe) is an essential micronutrient that participates in various biological processes important for plant growth. Ethylene production induced by Fe deficiency plays important roles in plant tolerance to stress induced by Fe deficiency. However, the activation and regulatory mechanisms of 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) genes in this response are not clear. In this study, we demonstrated that Fe deficiency increased the abundance of ACS2, ACS6, ACS7, and ACS11 transcripts in both leaves and roots as well as the abundance of ACS8 transcripts in leaves and ACS9 transcripts in roots. Furthermore, we investigated the role of mitogen-activated protein kinase 3 and 6 (MPK3/MPK6)-regulated ACS2/6 activation in Fe deficiency-induced ethylene production. Our results showed that MPK3/MPK6 transcript abundance and MPK3/MPK6 phosphorylation are elevated under conditions of Fe deficiency. Furthermore, mpk3 and mpk6 mutants show a lesser induction of ethylene production under Fe deficiency and a greater sensitivity to Fe deficiency. Finally, in mpk3, mpk6, and acs2 mutants under conditions of Fe deficiency, induction of transcript expression of the Fe-deficiency response genes FRO2, IRT1, and FIT is partially compromised. Taken together, our results suggest that the MPK3/MPK6 and ACS2 are part of the Fe starvation-induced ethylene production signaling pathway.

Identification of OsbHLH133 as a regulator of iron distribution between roots and shoots in Oryza sativa.

Iron (Fe) is an essential micronutrient element for plant growth. Regulation of Fe-deficiency signalling networks is one of the many functions reported for basic helix-loop-helix (bHLH) transcription factors in plants. In the present study, OsbHLH133 was found to be induced by Fe-deficiency conditions in Oryza sativa. Insertional inactivation of OsbHLH133 (bhlh133) resulted in growth retardation, with enhanced Fe concentration seen in shoots, and reduced Fe concentration in roots. Overexpression of OsbHLH133 had the opposite effect, that is resulted in an enhanced Fe concentration in roots and reduced Fe concentration in shoots and also in xylem sap. Microarray analysis showed that some of the genes encoding Fe-related functions were up-regulated under Fe-sufficient conditions, in bhlh133 mutant plants compared to wild-type plants. Significant differential expression of a number of signalling pathways, including calcium signalling, was also seen in bhlh133 plants compared to wild-type plants, independent of Fe conditions.