While myeloid-derived suppressor cells (MDSCs) have been reported to participate in the promotion of angiogenesis and tumor growth, little is known about their presence and function during perioperative period. Here, we demonstrated that human MDSCs expressing CD11b 1 , CD33 1 and HLA-DR -significantly increased in lung cancer patients after thoracotomy. CD11b 1 CD33 1 HLA-DR -MDSCs isolated 24 hr after surgery from lung cancer patients were more efficient in promoting angiogenesis and tumor growth than MDSCs isolated before surgical operation in allograft tumor model. In addition, CD11b 1 CD33 1 HLA-DR -MDSCs produced high levels of MMP-9. Using an experimental lung metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and Gr-1 1 CD11b 1 MDSCs at postoperative period were enhanced in proportion to the degree of surgical manipulation. We also examined that syngeneic bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of Gr-1 1 CD11b 1 MDSCs and further prevented lung metastasis formation in the mice undergoing laparotomy. Taken together, our results suggest that postoperatively induced MDSCs were qualified with potent proangiogenic and tumor-promotive ability and this cell population should be considered as a target for preventing postoperative tumor metastasis.Surgery excision of primary tumor is a mainstay of therapy in many tumor types, but emerging experimental and clinical evidence suggests that surgical intervention may promote the spreading and seeding of malignant cells and the growth of preexisting micrometastasis in some cancers. 1 Surgeryinduced stress can modify the neural, endocrine, inflammatory, metabolic and immunologic microenvironment of malignant cells. 2 Following a major surgery, cellular immunity remains suppressed for several days with decrease in circulating levels of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, dendritic cells (DCs) and T-helper cells. 2 The magnitude of this immune suppression is proportional to the degree of surgical manipulation. 3 Therefore, the immediate postoperative period may contribute substantially to the risk of subsequent emergence of metastasis, and perioperative modulations that reduce this risk may improve long-term outcome. 3,4 While the potential for surgical operation to attenuate antitumor cell-mediated immune response is well recognized, very few studies have been conducted to investigate immunosuppressive aspects in perioperative context.Myeloid-derived suppressor cells (MDSCs), a definition that reflects both their origin and function, represent a heterogeneous population of myeloid cells that inhibit antitumor immune response. 5 In humans, MDSCs are characterized by the cell surface expression of integrin CD11b, sialic acidbinding lectin CD33 and low expression of the MHC Class II molecule-HLA-DR. 6 The expression of CD14 and nuclear

In this paper we comprehensively survey the concept and strategies for building a resilient and integrated cyber-physical system (CPS). Here resilience refers to a 3S-oriented design, that is, stability, security, and systematicness: Stability means the CPS can achieve a stable sensing-actuation close-loop control even though the inputs (sensing data) have noise or attacks; Security means that the system can overcome the cyber-physical interaction attacks; and Systematicness means that the system has a seamless integration of sensors and actuators. We will also explain the CPS modeling issues since they serve as the basics of 3S design. We will use two detailed examples from our achieved projects to explain how to achieve a robust, systematic CPS design: Case study 1 is on the design of a rehabilitation system with cyber (sensors) and physical (robots) integration. Case Study 2 is on the implantable medical device design. It illustrates the nature of CPS security principle. The dominant feature of this survey is that it has both principle discussions and practical cyber-physical coupling design. 1

While monocytic myeloid-derived suppressor cells (M-MDSCs) have been reported to induce the development of regulatory T cells (Treg), little is known about their correlation with Treg during perioperative period. Here, we demonstrated that the M-MDSCs expressing CD11b+CD33+HLA-DR–CD14+ in lung cancer patients after thoractomy significantly increased in comparison with preoperation, and their accumulation linearly correlated with an increase in Treg. Surgery-induced M-MDSCs, in addition to have high arginase activity, were more efficient in suppressing T-cell proliferation. Furthermore, the surgery-induced Treg expressed high levels of Foxp3, PD-1 and CTLA-4. Surgery-induced M-MDSCs were more potent in expending Treg when cocultured with autologous T cells in vitro. Using a lung metastasis mouse model, we demonstrated that the M-MDSCs at postoperative period were significantly increased and linearly correlated with Treg. We also showed that all-trans retinoic acid significantly inhibited the induction and proliferation of M-MDSCs, suppressed expansion of Treg, and finally prevented tumor metastasis in the mice after tumor resection. Receiver operating characteristic analyses revealed the superiority of surgery-induced M-MDSCs and Treg to those at preoperative period as a prognostic marker for lung cancer patients. Taken together, our results link the presence of surgery-induced M-MDSCs with the emergence of Treg and identify M-MDSCs and Treg derived postoperatively as potential indicators of tumor metastasis.

IMPORTANCE: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) is a major public health concern since studies suggest that 1 in 3 infected with SARS-CoV-2 may develop PASC, including those without initial symptoms or with mild COVID-19 disease.1, 2 OBJECTIVE: To evaluate the timing, duration, and health impacts of PASC reported by a large group of primarily non-hospitalized COVID-19 survivors. DESIGN, SETTING, AND PARTICIPANTS: A survey of 5,163 COVID-19 survivors reporting symptoms for more than 21 days following SARS-CoV-2 infection. Participants were recruited from Survivor Corps and other online COVID-19 survivor support groups. MAIN OUTCOMES AND MEASURES: Participants reported demographic information, as well as the timing, duration, health impacts, and other attributes of PASC. The temporal distribution of symptoms, including average time to symptom onset and duration of symptoms were determined, as well as the perceived distress and impact on ability to work. RESULTS: On average, participants reported 21.4 symptoms and the number of symptoms ranged from 1 to 93. The most common symptoms were fatigue (79.0%), headache (55.3%), shortness of breath (55.3%), difficulty concentrating (53.6%), cough (49.0%), changed sense of taste (44.9%), diarrhea (43.9%), and muscle or body aches (43.5%). The timing of symptom onset varied and is best described as happening in waves. The longest lasting symptoms on average for all participants (in days) were "frequently changing" symptoms (112.0), inability to exercise (106.5), fatigue (101.7), difficulty concentrating (101.1), memory problems (100.8), sadness (99.2), hormone imbalance (99.1), and shortness of breath (96.9). The symptoms that affected ability to work were changing symptoms, inability to concentrate, fatigue, and memory problems, among others. Symptoms causing the greatest level of distress (on scale of 1 "none" to 5 "a great deal") were extreme pressure at the base of the head (4.4), syncope (4.3), sharp or sudden chest pain (4.2), brain pressure (4.2), headache (4.2), persistent chest pain or pressure (4.1), and bone pain in extremities (4.1). CONCLUSIONS AND RELEVANCE: PASC is an emerging public health priority characterized by a wide range of changing symptoms and hindering survivors' ability to work. PASC has not been fully characterized and the trajectory of symptoms and long-term outcomes are unknown. There is no treatment for PASC, and survivors report distress in addition to a host of ongoing symptoms. Capturing patient reports of symptoms through open-ended inquiry is a critical first step in accurately and comprehensively characterizing PASC to ensure that medical treatments and symptom management strategies best meet the needs of patients and help mitigate health impacts of this new disease.